高脂高糖膳食诱导脂联素基因敲除鼠血管钙化及其钙化机制的研究
|
摘要
第一部分脂联素基因敲除小鼠动脉钙化病理特征性观察
目的
观察脂联素基因敲除鼠组织病理学和组织化学的特性。
方法
40只6W龄小鼠随机分为5组(n=8),包括16只脂联素基因敲除鼠和野生型鼠24只。分别给予(前4组)高脂高糖膳食饲料和普通膳食,第5组腹腔注射链脲菌素1次(30mg/kg)再高脂高糖膳食喂养构建2型糖尿病模型鼠。10W后安乐死处死动物,摘眼球取血,分离血浆,采用酶法测定血糖浓度,放射免疫法测定血胰岛素水平。分离鼠胸主动脉置4%多聚甲醛固定,石蜡包埋,连续切片,行茜素红钙化染色。分离主动脉弓到髂骨分支的动脉,用比色法测定10%甲酸抽提的钙含量。超声破碎胸主动脉,离心后取上清液采用对硝基苯酚法测定ALP活性。用Bradford法测总蛋白含量。Western-blot检测Run x2蛋白表达。
结果
高脂高糖膳食喂养条件下,脂联素基因敲除鼠与链脲菌素干预鼠的血糖、血胰岛素水平明显高于野生型鼠。敲除鼠出现了严重的动脉钙化。脂联素基因敲除鼠动脉钙含量明显高于野生型鼠和链脲菌素干预鼠。与普通膳食身高喂养的小鼠比较,高脂高糖膳食组鼠ALP活性升高,敲除鼠升高更为明显。Runx2蛋白的表达脂联素基因敲除鼠明显高于野生鼠。
结论
在高脂高糖膳食喂养条件下,脂联素基因敲除鼠出现严重的2型糖尿病性动脉钙化,其机制可能与动脉中升高的ALP活性和Runx2蛋白的表达有关。
第二部分脂联素对钙化的血管平滑肌的影响
目的
探讨体外培养的钙化血管平滑肌细胞中脂联素受体的表达及其用重组脂联素干预后对钙化血管平滑肌的影响。
方法
剖杀用高脂高糖饮食喂养10W脂联素基因敲除鼠,分离主动脉行钙化动脉平滑肌细胞培养,应用免疫细胞化学方法鉴定血管平滑肌细胞。应用PT-PCR和Western-blot分别测定脂联素受体mRNA和蛋白在钙化血管平滑肌细胞中的表达情况。取不同浓度的(0,3,10,30μg/mL)脂联素干预钙化的血管平滑肌细胞48h,采用对硝基苯酚法测定碱性磷酸酶(ALP)活性,放射免疫法检测骨钙素(OC)含量,Western-blot检测Runx2蛋白的表达。用30μg/mL的脂联素干预20d后,1%茜素红进行钙化结节染色。
结果
钙化血管平滑肌细胞α-肌动蛋白(a-actin)的免疫细胞化学染色证定培养细胞为血管平滑肌细胞,且该细胞能自发形成钙化结节。钙化的平滑肌细胞主要表达脂联素受体R1 mRNA和蛋白。脂联素干预能使钙化的血管平滑肌细胞ALP活性降低,OC分泌减少,Runx2蛋白表达下降,并且呈剂量依赖关系。用30μg/mL脂联素干预20d后,钙化血管平滑肌细胞的钙化结节得到显著抑制。
结论
脂联素能抑制培养的钙化血管平滑肌细胞的钙化,其机制可能通过与钙化血管平滑肌细胞表达AdipoR1结合发挥作用。
第三部分脂联素通过AdpoRl/p38信号途径抑制CVSMCs体外成骨样钙化
目的
探讨脂联素抑制脂联素基因敲除鼠钙化血管平滑肌细胞体外成骨样钙化的作用机制。
方法
用30μg/mL脂联素干预钙化血管平滑肌细胞,0、5、30、60min后抽提细胞总蛋白,用Western-blot方法检测细胞传导信号p-JNK、JNK、p-p38、p38、p-ERK、ERK蛋白在细胞内的表达。合成脂联素受体R1的小干扰RNA (AdipoRl-SiRNAs)抑制AdipoRl表达,观察AdipoR1、p-p38和p38蛋白在钙化血管平滑肌细胞的表达。加入p38信号传导抑制剂SB203580,联合AdipoRl-SiRNAs,用对硝基苯酚法测定钙化血管平滑肌细胞碱性磷酸酶(ALP)的活性。
结果
脂联素可诱导钙化血管平滑肌细胞p38磷酸化,但对JNK和ERK的激活无作用。SiRNAs-AdipoRl转染可阻断AdipoRl表达,可抑制p38磷酸化。p38抑制剂SB203580和SiRNAs-AdipoR1可减弱脂联素对钙化血管平滑肌细胞ALP活性的影响。说明p38信号通路在脂联素抑制钙化血管平滑肌细胞的钙化中起重要作用。
结论
脂联素可通过AdipoR1/p38信号途径抑制钙化血管平滑肌细胞体外成骨样钙化。
Part one Observation on pathological character of arterial calcification in adiponectin knockout mice
Objective to observe on histopathologic and histochemical characters in adiponectin knockout (Adipo-/-) mice.
Methods
Forty of 6 weeks old mice were divided at random into 5 groups (n=8 per group). Group 1:wild type (WT) mice fed high-fat/high-sucrose (HF/HS)diet. Group 2:Adipo-/-mice fed HF/HS diet. group3:WT mice fed normal chow diet. Group 4:Adipo-/-mice fed normal diet. Goup 5: WT mice intraperitoneal injected streptozotocin (30mg/kg body weight) 1 time and then fed HF/HS diet developing a model of type 2 diabetes mellitus. After 10 weeks, the mice were euthanized.Blood was collected from retro-orbital venous plexus, and plasma concentrations of glucose were determined enzymatically.Insulin concentrations were determined by radioimmunoassay. The thoracic aortas were dissected, and then aortas were fixed in 4% paraformaldebyde. Alizarin Red S staining was used to detect calcification. Aortic segments from aorta arch to the iliac bifurcation were removed, then calcium was extracted with 10% formic acid and the colorimetric quantification of calcium was achieved. The thoracic aorta was homogenized by ultrasounds, the ALP activity of supernatant was measured by spectrophotometric measurement of P-nitrophenol release. Total protein was determined using Bradford protein assay.Runx2 protein expression was analyzed by Western-blot.
Results
Adipo-/-mice and the model mice of type 2 diabetes mellitus from the HF/HS diet and displayed high fasting glucose levels, and high fasting plasma insulin levels, these were significantly higher than those in other mice. Severe aortic calcification could be seen in Adipo-/-mice, and aortic calcium contents in Adipo-/-mice with HF/HS diet increased more obviously than WT mice and streptozotocin injected mice compared with the normal diet.WT mice with HF/HS showed significantly elevated ALP activity, but Adipo-/-mice with HF/HS diet increased more obviously. The expression of Runx2 protein in aorta of Adipo-/-mice with HF/HS diet was higher than that of WT diabetic mice (group 5).
Conclusion
Our work demonstrated that Adipo-/-mice developed severe diabetic arterial calcification, and the mechanism was associated with the elevated ALP activity and Runx2 protein expression in the arota.
Part two The effects of adiponectin on cultured calcifying vascular smooth muscle cells
Objective
To investigate the expression of adiponectin receptor in culured calcifying vascular smooth muscle cells (CVSMCs) in vitro and the effects of adiponectin on CVSMCs.
Methods
6 weeks old male adiponectin knockout mice (Adipo-/-) were fed high-fat/high-sucrose (HF/HS) diet diet for 10 weeks, then these mice were sacrificed, the aorta removed, and the CVSMCs were cultured. The culured CVSMCs were identifed by their positive staining with monoclonal antibody a-actin. The expression of adiponectin receptor mRNA and protein in CVSMCs were detected using RT-PCR and western-blot. When the cells were treated with adiponectin at 3μg/mL,10μg/mL,30μg/mL for 48h, the alkaline phosphatase (ALP) activity was measured by spectrophotometric measurement of P-nitorphenol release, osteocalcin(OC) was detected by radioimm-unoassay, and Runx2 expression was analyzed by Western-blot. The calcified nodules were stained by 1% Alizarin Red S in the presence of 30μg/mL for 20 days.
Results
The immunocytochemical stain for smooth muscle a-actin confirmed vascular smooth muscle cells (VSMCs) pheotype and the multicellular nodules spontaneously appeared in VSMCs culture. Adiponectin receptor R1 (AdipoRl) and Adiponectin receptor R2 (AdipoR2) mRNA were expressed in CVSMCs, but only AdipoRl Protein was detected. Adiponectin suppressed ALP activity, OC secretion and Runx2 protein expression in a dose-dependent manner. Adiponectin also decreased calcified nodules formation in at 30μg/mL concentration for 20 days.
Conclusion
These data indicated that adiponectin significantly inhibited cultured CVSMCs calcification in vitro may mediate by AdipoR pathway.
Part three Adiponectin inhibited osteoblastic calcification of CVSMCs via AdipoRl/p38 signaling pathway in vitro
Objective
To investigate mechanisms of adiponectin inhibited osteoblastic calcification of cultured calcifying vascular smooth muscle cells (CVSMCs) in vitro.
Methods
After in the presence of 30μg/mL adiponectin for 0,5,30,60min, the total protein were extracted. The protein of P-JNK, JNK, P-p38, p38, P-ERK, ERK were detected using Western-blot method. Small interfering RNA (SiRNAs) was used to down-regulate the expression of AdipoRl in CVSMCs, then AdipoRl, p-p38, p38 were analysed. The ALP activity was measured by spectrophotometric measurement of p-nitrophenol release when SB 203580 blocked p38 or SiRNAs blocked AdipoRl.
Results
Adiponectin induced activation of p38, but not JNK and ERK in CVSMCs. These effects were blocked by suppression of AdipoRl with SiRNA. Furthermore, pretreatment of CVSMCs with p38 inhibitor (SB203580) or SiRNAs-AdipoRl abolished adiponectin induced ALP activity. These date suggested that p38 signaling pathway played an important role in inhibiting the calcification of CVSMCs.
Conclusion
Our date indicated adiponectin inhibited osteoblastic calcification of CVSMCs via AdipoR1/p38 signaling pathway.
目的
观察脂联素基因敲除鼠组织病理学和组织化学的特性。
方法
40只6W龄小鼠随机分为5组(n=8),包括16只脂联素基因敲除鼠和野生型鼠24只。分别给予(前4组)高脂高糖膳食饲料和普通膳食,第5组腹腔注射链脲菌素1次(30mg/kg)再高脂高糖膳食喂养构建2型糖尿病模型鼠。10W后安乐死处死动物,摘眼球取血,分离血浆,采用酶法测定血糖浓度,放射免疫法测定血胰岛素水平。分离鼠胸主动脉置4%多聚甲醛固定,石蜡包埋,连续切片,行茜素红钙化染色。分离主动脉弓到髂骨分支的动脉,用比色法测定10%甲酸抽提的钙含量。超声破碎胸主动脉,离心后取上清液采用对硝基苯酚法测定ALP活性。用Bradford法测总蛋白含量。Western-blot检测Run x2蛋白表达。
结果
高脂高糖膳食喂养条件下,脂联素基因敲除鼠与链脲菌素干预鼠的血糖、血胰岛素水平明显高于野生型鼠。敲除鼠出现了严重的动脉钙化。脂联素基因敲除鼠动脉钙含量明显高于野生型鼠和链脲菌素干预鼠。与普通膳食身高喂养的小鼠比较,高脂高糖膳食组鼠ALP活性升高,敲除鼠升高更为明显。Runx2蛋白的表达脂联素基因敲除鼠明显高于野生鼠。
结论
在高脂高糖膳食喂养条件下,脂联素基因敲除鼠出现严重的2型糖尿病性动脉钙化,其机制可能与动脉中升高的ALP活性和Runx2蛋白的表达有关。
第二部分脂联素对钙化的血管平滑肌的影响
目的
探讨体外培养的钙化血管平滑肌细胞中脂联素受体的表达及其用重组脂联素干预后对钙化血管平滑肌的影响。
方法
剖杀用高脂高糖饮食喂养10W脂联素基因敲除鼠,分离主动脉行钙化动脉平滑肌细胞培养,应用免疫细胞化学方法鉴定血管平滑肌细胞。应用PT-PCR和Western-blot分别测定脂联素受体mRNA和蛋白在钙化血管平滑肌细胞中的表达情况。取不同浓度的(0,3,10,30μg/mL)脂联素干预钙化的血管平滑肌细胞48h,采用对硝基苯酚法测定碱性磷酸酶(ALP)活性,放射免疫法检测骨钙素(OC)含量,Western-blot检测Runx2蛋白的表达。用30μg/mL的脂联素干预20d后,1%茜素红进行钙化结节染色。
结果
钙化血管平滑肌细胞α-肌动蛋白(a-actin)的免疫细胞化学染色证定培养细胞为血管平滑肌细胞,且该细胞能自发形成钙化结节。钙化的平滑肌细胞主要表达脂联素受体R1 mRNA和蛋白。脂联素干预能使钙化的血管平滑肌细胞ALP活性降低,OC分泌减少,Runx2蛋白表达下降,并且呈剂量依赖关系。用30μg/mL脂联素干预20d后,钙化血管平滑肌细胞的钙化结节得到显著抑制。
结论
脂联素能抑制培养的钙化血管平滑肌细胞的钙化,其机制可能通过与钙化血管平滑肌细胞表达AdipoR1结合发挥作用。
第三部分脂联素通过AdpoRl/p38信号途径抑制CVSMCs体外成骨样钙化
目的
探讨脂联素抑制脂联素基因敲除鼠钙化血管平滑肌细胞体外成骨样钙化的作用机制。
方法
用30μg/mL脂联素干预钙化血管平滑肌细胞,0、5、30、60min后抽提细胞总蛋白,用Western-blot方法检测细胞传导信号p-JNK、JNK、p-p38、p38、p-ERK、ERK蛋白在细胞内的表达。合成脂联素受体R1的小干扰RNA (AdipoRl-SiRNAs)抑制AdipoRl表达,观察AdipoR1、p-p38和p38蛋白在钙化血管平滑肌细胞的表达。加入p38信号传导抑制剂SB203580,联合AdipoRl-SiRNAs,用对硝基苯酚法测定钙化血管平滑肌细胞碱性磷酸酶(ALP)的活性。
结果
脂联素可诱导钙化血管平滑肌细胞p38磷酸化,但对JNK和ERK的激活无作用。SiRNAs-AdipoRl转染可阻断AdipoRl表达,可抑制p38磷酸化。p38抑制剂SB203580和SiRNAs-AdipoR1可减弱脂联素对钙化血管平滑肌细胞ALP活性的影响。说明p38信号通路在脂联素抑制钙化血管平滑肌细胞的钙化中起重要作用。
结论
脂联素可通过AdipoR1/p38信号途径抑制钙化血管平滑肌细胞体外成骨样钙化。
Part one Observation on pathological character of arterial calcification in adiponectin knockout mice
Objective to observe on histopathologic and histochemical characters in adiponectin knockout (Adipo-/-) mice.
Methods
Forty of 6 weeks old mice were divided at random into 5 groups (n=8 per group). Group 1:wild type (WT) mice fed high-fat/high-sucrose (HF/HS)diet. Group 2:Adipo-/-mice fed HF/HS diet. group3:WT mice fed normal chow diet. Group 4:Adipo-/-mice fed normal diet. Goup 5: WT mice intraperitoneal injected streptozotocin (30mg/kg body weight) 1 time and then fed HF/HS diet developing a model of type 2 diabetes mellitus. After 10 weeks, the mice were euthanized.Blood was collected from retro-orbital venous plexus, and plasma concentrations of glucose were determined enzymatically.Insulin concentrations were determined by radioimmunoassay. The thoracic aortas were dissected, and then aortas were fixed in 4% paraformaldebyde. Alizarin Red S staining was used to detect calcification. Aortic segments from aorta arch to the iliac bifurcation were removed, then calcium was extracted with 10% formic acid and the colorimetric quantification of calcium was achieved. The thoracic aorta was homogenized by ultrasounds, the ALP activity of supernatant was measured by spectrophotometric measurement of P-nitrophenol release. Total protein was determined using Bradford protein assay.Runx2 protein expression was analyzed by Western-blot.
Results
Adipo-/-mice and the model mice of type 2 diabetes mellitus from the HF/HS diet and displayed high fasting glucose levels, and high fasting plasma insulin levels, these were significantly higher than those in other mice. Severe aortic calcification could be seen in Adipo-/-mice, and aortic calcium contents in Adipo-/-mice with HF/HS diet increased more obviously than WT mice and streptozotocin injected mice compared with the normal diet.WT mice with HF/HS showed significantly elevated ALP activity, but Adipo-/-mice with HF/HS diet increased more obviously. The expression of Runx2 protein in aorta of Adipo-/-mice with HF/HS diet was higher than that of WT diabetic mice (group 5).
Conclusion
Our work demonstrated that Adipo-/-mice developed severe diabetic arterial calcification, and the mechanism was associated with the elevated ALP activity and Runx2 protein expression in the arota.
Part two The effects of adiponectin on cultured calcifying vascular smooth muscle cells
Objective
To investigate the expression of adiponectin receptor in culured calcifying vascular smooth muscle cells (CVSMCs) in vitro and the effects of adiponectin on CVSMCs.
Methods
6 weeks old male adiponectin knockout mice (Adipo-/-) were fed high-fat/high-sucrose (HF/HS) diet diet for 10 weeks, then these mice were sacrificed, the aorta removed, and the CVSMCs were cultured. The culured CVSMCs were identifed by their positive staining with monoclonal antibody a-actin. The expression of adiponectin receptor mRNA and protein in CVSMCs were detected using RT-PCR and western-blot. When the cells were treated with adiponectin at 3μg/mL,10μg/mL,30μg/mL for 48h, the alkaline phosphatase (ALP) activity was measured by spectrophotometric measurement of P-nitorphenol release, osteocalcin(OC) was detected by radioimm-unoassay, and Runx2 expression was analyzed by Western-blot. The calcified nodules were stained by 1% Alizarin Red S in the presence of 30μg/mL for 20 days.
Results
The immunocytochemical stain for smooth muscle a-actin confirmed vascular smooth muscle cells (VSMCs) pheotype and the multicellular nodules spontaneously appeared in VSMCs culture. Adiponectin receptor R1 (AdipoRl) and Adiponectin receptor R2 (AdipoR2) mRNA were expressed in CVSMCs, but only AdipoRl Protein was detected. Adiponectin suppressed ALP activity, OC secretion and Runx2 protein expression in a dose-dependent manner. Adiponectin also decreased calcified nodules formation in at 30μg/mL concentration for 20 days.
Conclusion
These data indicated that adiponectin significantly inhibited cultured CVSMCs calcification in vitro may mediate by AdipoR pathway.
Part three Adiponectin inhibited osteoblastic calcification of CVSMCs via AdipoRl/p38 signaling pathway in vitro
Objective
To investigate mechanisms of adiponectin inhibited osteoblastic calcification of cultured calcifying vascular smooth muscle cells (CVSMCs) in vitro.
Methods
After in the presence of 30μg/mL adiponectin for 0,5,30,60min, the total protein were extracted. The protein of P-JNK, JNK, P-p38, p38, P-ERK, ERK were detected using Western-blot method. Small interfering RNA (SiRNAs) was used to down-regulate the expression of AdipoRl in CVSMCs, then AdipoRl, p-p38, p38 were analysed. The ALP activity was measured by spectrophotometric measurement of p-nitrophenol release when SB 203580 blocked p38 or SiRNAs blocked AdipoRl.
Results
Adiponectin induced activation of p38, but not JNK and ERK in CVSMCs. These effects were blocked by suppression of AdipoRl with SiRNA. Furthermore, pretreatment of CVSMCs with p38 inhibitor (SB203580) or SiRNAs-AdipoRl abolished adiponectin induced ALP activity. These date suggested that p38 signaling pathway played an important role in inhibiting the calcification of CVSMCs.
Conclusion
Our date indicated adiponectin inhibited osteoblastic calcification of CVSMCs via AdipoR1/p38 signaling pathway.
引文
[1]Wallin R, Wajih N, Greenwood GT, et al. Arterial calcification:a review of machanisms, animal modals and the prospects for therapy. Med Res Rev,2001,21: 274-301
[2]Jono S, NisbizawaY, Shioi A, etal.1.25-Dihydroxyvitam in D3 increases in vitro vascular calcification by modulating secretion of endogenous parathyroid hormone-related peptide. Circulation,1998,98:1302-1306
[3]Chen NX, Moe SM. Arterial Calcification in diabetes. C URR Diab Rep, 2003,3:28-32
[4]Johnson RC, Leopold JA. Loscalzo J. vascular calcification pathobiological mechanisms anol clinical implications, Circ Res,2006,99:1044-1059
[5]Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to C1q produced exclusively in adipocyte J Biol Chem,1995,270:26746-26749
[6]Maeda K, Okubo K, Shimomural I, et al. cDNA clong and expression of a novel adipose specific collagen-like factor, apMl (Adipose Most abundant Gene transcript 1). Biochem Biophys Res Commun,1996,221:286-289
[7]Hu E, Liang P, Spieglman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Bio Chem,1996,271:10697-10703
[8]Nakano Y, Tobe T, Choi-Miura NH, et al. Isolation and characterization of GBP28,a novel gelatin-binding protein purified from human plasma. J Biochem,1996;20:803-812
[9]Arita Y, Kihara S, Ouchi N, et al. Paradoxiclal decrease of an adipose-specific protein,adiponectin in obesity. Biochem Biophys Res Commun,1999,257:79-83
[10]Pajvani UB, Du X, Combs TP, et al. Structure-function studies of the adipoc yte-secreted hormone Acrp30/adiponectin implication for metabolic regulation and bioactivity. J Biol Chem,2003,278:9073-9085
[11]Kishida K, Nagaretani H, Kondo H, et al. Disturbed secretion of mutant adiponectin associated with the metabolic syndrome. Biochem Biophys Res Commun,2003,306:286-292
[12]Kadowaki T and Yamauchi T. Adiponectin and diponectin receptors Enaloerine Reviews,2005,26:439-451
[13]Hotta K, Funahashi T, Bodkin NL. etal. Circulating concentrations of the adipocyte protein adiponectin are decreased in paralkl with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkey. Diabetes,2001,50: 1126-1133
[14]Gracheli CM.Vadcular calcification mechanisms. J Am Soc Nephrol, 2004,15:2959-2964
[1]Francke S. ManraiM, Lacquemant C, et al. A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on Chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q 27. Hum Md Genet, 2011,10:2751-2765
[2]Viooonet N, Hani EH, Dupnt S, et al. Genome-wide search for type 2 diabetes-susceptibility genes in French whites, evidence for a novel susceptibility locus for early-onset diabetes on Chromosome 3q27-gter and independent replication of type 2 diabetes locus on Chromosome 1q21-q24. Am J Hum Genet,2000, 67:1470-1480
[3]Harak, Boutin P, Mori Y, et al. Genetic variation in the gene encoding adiponectin is associated with an increased risk of Type 2 diabetes in the Japanese population. Diabetes,2002,51:536-540
[4]Spranger J. Kroke A. Mohlig M et al. Adiponectin and protection against type 2 diabetes mellitus. Lancet,2003,361:226-228
[5]Hota K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel adipose-specific protein adiponectin in type 2 deabetic patients. Arterioscler Thromb vasc Biol,2000,20:1595-1599
[6]任维华,李西华,王芳等.Adiponectin基因剔除LacZ基因敲入小鼠模型的建立。生物化学与生物物理进展,2006,33：846-853
[7]Kemedy AR, Pissios P, Otu H, et al. A high-fat ketogenic diet induces a unique metabolic state in mice. Am J Physiol Endocrinol Metab,2007.292: E1724-1739
[8]Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to C1q produced exclusively in adipocyte.J Biol Chem,1995,270:26746-26749
[9]Maeda K, Okubo K, Shimomural I, et al. cDNA clong and expression of a novel adipose specific collagen-like factor, apMl (Adipose Most abundant Gene transcript 1). Biochem Biophys Res Commun,1996,221:286-289
[10]Hu E, Liang P, Spieglman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Bio Chem,1996,271:10697-10703
[11]Nakano Y, Tobe T, Choi-Miura NH, et al. Isolation and characterization of GBP28,a novel gelatin-binding protein purified from human plasma. J Biochem, 1996,20:803-812
[12]Matsuzawa Y, Shimomura I, Kihara S, et al. Importance of adipocytokines in obesity-related diseases. Horm Res,2003,60 Suppl 3:56-59
[13]Satoh H, Audrey N, Trujillo M, et al. Adenovirus-mediated adiponectin expression augments akeletal muscle insulin sensitivity in male Wistar rats. Diabetes, 2005,54:1304-1313
[14]Ouchi N, Kihara S, Funashashi T, et al. Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol.2003,14:561-566
[15]Hotta K, Funahashi T, Bodkin NL, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes,2001, 50:1126-1133
[16]Yamauchi T, Hara K, Kubota N, et al. Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine. Curr Drug Targets Immune Endocr Metabol Disord,2003:243-254
[17]Parhami F, Tintut Y, Patel JK et al. Regulation of vascular Calcification in atherosclerosis. Z. karadiol,2001,90:27-30
[18]Wallin R, Wajih N, Green wood GT, et al, Arterial Calcification:a review of mechanisms, animal models and the prospects for therapy. Med Res Rev,2001, 21:274-301
[19]Matasuzawa Y, Funahashi T, Kihara S, et al. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol,2004,24:29-33
[20]Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadipo-nectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol, 2003,23:85-89
[21]Maahs DM,Ogden LG, Kinney GL et al. Low plasma adiponatin levels predict progress of coronary artery calcification. Circulation,2005,116:747-753
[22]Steffes MW, Gross MD, Lee DH, et al. Adiponectin, visceral fat, oxidative stress, and early macrovascular diaease:the coronary artery risk development in young adults study. Obesity,2006,14:319-326
[23]Im JA, Kim SH, Lee JW, et al. Association between hypoadiponectinemia and cardiovascular risk factors in nonobese healthy adults. Metabolism,2006,55: 1546-1550
[24]Kim OY, Koh SJ, Jang Y, et al. Plasma adiponectin is related to other cardiovascular risk factors in nondiabetic Korean men with CAD, independent of adiposity and cigarette smoking:cross-sectional analysis. Clin Chim Acta,2006,370: 63-71
[25]Chen MP, Tsai JC, Chung FM, et al. Hypoadiponectinemia is associated with ischemic cerebrovascular disease. Arterioscler Thromb Vasc Biol,2005,25: 821-826
[26]Dunajska K, Milewicz A, Jedrzejuk D, et al. Plasma adiponectin concentration in relation to severity of coronary atherosclerosis and carkiovascular risk factors in middle-aged men. Endocrine,2004,25:215-221
[27]Ouchi N, Kihara S, Funahashi T, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation, 2003,107:671-674
[28]Zietz B, Herfarth H, Paul G, et al. Adiponectin represents and independent cardiovascular risk factor predicting serum HDL-Cholesterol levels in type 2 diabetes. FFBS Lett,2003,545:103-104
[29]Teschritter O, Fritsche A, Thamer C, et al. Plasma adiponectin concentration predict insulin sensitivity of both glucose and lipid metabolism. Diabetes,2003, 52:239-243
[30]Hulthe J, Hulten LM, Fagerberg B. Low adipocyte-derived plasma protein adiponectin concentrations are associated with the metabolic syndrome and small dense low-density lipoprotein particles:Atherosclerosis and insulin resistance study. Metabolism,2003,52:1612-1614
[31]姚君厘.糖尿病和大血管病变.上海医药,2006,27：253-256
[32]Johnson RC, Leopold JA, Loscalzo J. Vascular calcification pathobiological mechanisms and clinical implications. Circ. Res,2006,99:1044-1059
[33]Chen NX, Moe SM. Arterial calcification in diabetes. Current Diabetes Reports,2003,3:28-32
[34]Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocrine Reviews,2005,26:439-451
[35]Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab,2004,89:2548-2556
[36]刘亚平,季虹,荣海欣等.2型糖尿病雌性大鼠骨代谢的特点.中国骨质疏松杂志,2008,14：35-38
[37]何清华,周迎生,王征等.2型糖尿病模型制备的影响因素及其特点.中国实验动物学报,2007,15：425-429
[38]余传林,朱正光,雷林生等.链脲佐菌素糖尿病模型动物血糖及体征动态变化的研究.南方医科大学学报,2008,28：132-133
[39]吴胜英,潘春不,齐永芬等.雌激素减轻大鼠血管钙化的实验研究.郧阳医学院学报,2004,23：328-331
[40]Hoshi K, Ejiri S. Ozawa H. Localizational alterations of calcium, phosphorus and calcificating-related organics such as proteoglycans and alkaline phosphatase during bone calcification. J Bone Miner Res,2001,16:289-298
[41]Shioo A. Nishizawa Y, Jono S, et al. β-Glycerohosphate calcification in cultured bovine vascular smooth muscle cells. Arterioscler Thromb vasc Biol, 1995,15:2003-2009
[42]Proudfoot D, Skepper JN, Shanahan CM, et al. Calcification of human vascular cells in vitro is correlated with high levels of matrix Glaprotein and low levels of osteopontin expression. Arterioscler Thromb vasc Biol,1998,18:379-388
[43]Wennberg C, Hessle L, Lundberg P, et al. Functional Characterization of osteoblasts and osteoclasts from alkaline phosphatase knaeout mice. J. Bone Miner Res,2000,15:1879-1888
[44]Stock M. otto F. Control of Runx2 isoform espression:the role of promoters and enhancers J Cell Biochem,2005,95:506-517
[45]Enomoto H, Furuichi T, Zanma A, et al. Runx2 deficiency in chondrocytes causes adipogenic changes in vitro. J Cell Sci,2004,117:417-425
[46]Gersbach CA, Byersb A, Pavlath GK,et al. Runx2/CBFα1 stimulates trans differentiation of primary skeletal myoblasts into a mineralizing osteoblastic phentype. Exp cell Res,2004,300:406-417
[47]Chen NX, Duan D, ONeil KD, et al. High glucose increases the expression of cbfal and BMP-2 and enhances the calcification of vasculan smooth muscle cells. Nephrol Dial Transplant,2006,21:3435-3442
[1]ketteler M, Giachellic. Novel insights into vascular calcification. kidney Int. Suppl,2006,105:s5-9
[2]Johnson RC, Leopold JA, Loscalzo J. Vascular calcification pathobiological mechanisms and clinical implications. Circ Res,2006,99:1044-1059
[3]Giachelli CM. Vascular calcification mechanisms.J Am Soc Nephrol.2004, 15:2959-2964
[4]Yamauchi I, Kamon I, Iro Y et al.Cloning of adiponectin receptors that mediate antidiabetic metabolic cffects.Narure,2003,423:762-769
[5]Civitarese AE,Jenkinson CP,Richardson D,et al.Adiponectin receptors gene expression and insulin sensitivity in non-diabetic Mexican Amerivan with or without a family history of Type 2 diabetes.Diabetologia,2004,47:816-820
[6]Berner HS, Lyngstadaas SP, Spahr A,et al. Adiponectin and its receptors are expressed in bone-forming cells. Bone,2004,35:842-849
[7]Luo XH, Guo LJ, Yuan LQ et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res,2005, 309:99-109
[8]Luo XH, Guo LJ, Xie H et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts via the MAPK signaling pathway. J Bone Miner Res,2006,21:1648-1656
[9]Parhami F,Tintut T,Patel JK, et al. Regulation of vascular calcification in atherosclerosis Z kardiol,2001,90:27-30
[10]Cozzolino M, Dusso AS, Slatopolsky E. Role of calcium-phosphate product and bone-associated proteins on vascular calcification in renal failure. J Am Soc Nephrol,2001,12:2511-2516
[11]Chen NX, Duan D, Moe SM, et al. High glucose increases the expression of Cbfa1 and BMP-2 and enhances the calcification of vascular smooth muscle cells. Nephrol Dial Transplant,2006,21:3435-3442
[12]Ding HT, Wang CG, Zhang TL, et al. Fibronectin enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells via ERK pathway. J Cell Biochem,2006,99:1343-1352
[13]Simionescu A, Philips K, Vyavahare N. Elastin-derived peptides and TGF-betal induce osteogenic response in smooth muscle cells. Biochem Biophys Res Commun.2005,334:524-532
[14]Campbell GR,Campbell JH. Vascular smooth muscle and arterial calcification. Z Kardiol,2000,89:254-262
[15]Steitz SA, Speer MY, Curinga G, et al. Smooth muscle cell phenotypic transition associated with calcification-Upregulation of Cbfal and downregulation of smooth muscle lineage markers. Circ Res,2001,89:1147-1154
[16]Kobayashi R, Kubota T, Hidaka H, et al. Purification, characterization, and partial sequence analysis of a new 25-kDa actin binding protein from bovine aorta:a SM22 homologue. Biochem Biophys Res Commun,1994,198:1275-1280
[17]Matasuzawa Y, Funahashi T, Kihara S, et al. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol,2004,24:29-33
[18]Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadipo-nectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol,2003, 23:85-89
[19]Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of family of soluble defense collagens,negatively regulates the grouth of myelom-onocytic progenitors and the functions of macrophages. Blood,2000,96:1723-1732
[20]Kadowaki T, Yanauchi T.Adiponectin and adiponectin receptors.Endocr Rev 2005,26:439-451
[21]Shioi A, NishizawaY,Jono S, et al. B-Glycerophosphate accelerates calcification in culture bovine vascular smooth muscle cells.Arterioscler Thromb Vasc Biol,1995,15:2003-2009
[22]Proudfoot D, Skepper JN, Shanahan CM, et al. Calcification of human vascular ceoos in vitro is correlated with high levels of matris Glaprotein and Low levels of osteopontin expresion.Arterioscler Thromb Vasc Bid,1998,18:379-388
[23]Bellows CG, Aubin JE, Heersche JN.Initiation and progression of minerolization of bone nodules formal in vitro:the role of alkaline phosphatase and organic phosphate. Bone Mier,1991,14:27-40
[24]Gundberg CM. Biochemical markers of bone formation. Clin Lab Med, 2000,20:489-501
[25]Chen NX, Duan D, Moe SM, et al. High glucose increases the expression of Cbfal and BMP-2 and enhances the calcification of vascular smooth muscle cells. Nephrol Dial Transplant,2006,21:3435-3442
[26]Ding HT, Wang CG, Zhang TL, et al. Fibronectin enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells via ERK pathway. J Cell Biochem,2006,99:1343-1352
[27]王宇政,王土雯,佟万仁等.TGF-B对血管钙化的影响.心脏杂志,2001,13：170-172
[28]KomoRi T.Regulation of skeletao development by the Runx family of transcription factors. J cell Biochem,2005,95:445-453
[29]Nman ck. Shore P. the osteoblast transcription factor RunX2 is expressed in mammary epitheliao ceoos and mediates osteopontin expression. J Biol Chen,2003, 278:684-689
[30]Giachell CM. Ectopic Calcification:new concepts in cellular regulation. Z kardiol,200190:31-37
[31]Watson KE, Parhami F, Shin V, et al. Fibronectin and collagen I matrixes promote calcification of vascular cells in vitro, whereas collagen IV matrix is inhibitory. Arterioscler Thromb vasc Biol,1998,18:1964-1971
[32]Shioi A, Nishizawa Y, Jono S, et al. β-Glycerophosphate accelerates calcification in cultured bovine vascular smooth muscle cells. Arterioscler Thromb Vasc Biol,1995,15:2003-2009
[33]Yang H, Curinga G, Giachelli CM. Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro. Kidney Int,2004,66: 2293-2299
[34]Jono S, McKee MD, Murry CE, et al. Phosphate regulation of vascular smooth muscle cell calcification. Circ Res,2000,87:e10-e17
[35]Sowa H, Kaji H, Yamaguchi T, et al. Smad3 promotes alkaline phosphatase activity and mineralization of osteoblastic MC3T3-E1 cells. J Bone Miner Res,2002, 17:1190-1199
[36]Noth U, Tuli R, Seghatoleslami R, et al. Activation of p38 and Smads mediates BMP-2 effects on human trabecular bone-derived osteoblasts, Exp Cell Res, 2003,291:201-211
[37]Yang S, Wei D, Wang D, et al. In vitro and in vivo synergistic interactions between the Runx2/Cbfal transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation. J Bone Miner Res,2003,18:705-715.
[1]Berner HS, Lyngstadoas SP, Spahr A, et al. Adiponectin and its receptors are expressed in bone forming cells. Bone,2004,35:842-849
[2]Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res,2005, 309:99-109
[3]Johnson RC, Leopold JA, Loscalzo J. Vascular calcification pathobiological mechanisms and clinical implications. Circ Res,2006,99:1044-1059
[4]Chen NX and Moe SM. Arterial calcification in diabetes. Current Diabetes Reports,2003,3:28-32
[5]Yamauchi T, Kamon J, Ito Y, et al. Cloning of Adiponectin receptors that mediate antidiabetic metabolce effects. Nature,2003,423:762-769
[6]Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both liporatrophy and obesity. Natl Med, 2001,7:941-946
[7]Weyer C, Funahash T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab,2001,86:1930-1935
[8]Yameuchi T, Hara K, Kabota N, et al. Dual roles of adiponectin/acrp30 in vivo as an anti-atherogenic adipokine. Curr Drug Targets Immune Endocri Metabol Disord,2003,3:243-254
[9]Wang H, Zhang HL, Jia YW, et al. Adiponectin receptors I gene (adipoR I) as a candidate for type 2 diabetes and insulin resistance. Diabetes,2004,53: 2132-2136
[10]Inukai K, Nakashima Y, Watanabe M, et al. Regulation of adiponectin receptor gene expression in diabetic mice. Am J Physiol Endocrnol Mctab,2005, 288:876-882
[11]Civitarese AE, Jenkinson CP, Richardson D, et al. Adiponectin receptors gene expression and insulin sensitivity in mon-diabetic Mexican American with or without a family history of type 2 diabetes. Diabetologia,2004,47:816-820
[12]Yamauchi T, Kamon J, Waki H, et al. Globular adiponectin protected ob/ob mice fromdiabetes and apoE deficient mice from atherosclerosis. J Bid Chem, 2003,278:2461-2468
[13]Gallea S, Lallemand F, Atfi A, et al. Activation of mitogen-activatec protein kinase cascades is involved in regulation of bone morphogenetic protein-2-induced osteoblast differentiation in pluripotent C2C12 cells. Bone,2001,5:491-498
[14]Celil AB, Campbell PG. BMP-2 and Insulin-like Growth Factor-I Mediate Osterix (Osx) Expression in Human Mesenchymal Stem Cells via the MAPK and Protein Kinase D Signaling Pathways. J Biol Chem,2005,36:31353-31359
[15]Park BH, Qiang L, Farmer SR. Phosphorylation of C/EBPβat a consensus extracellular signal-regulated kinase/glycogen synthase kinase 3 site is required for the adiponectin gene expression during the differentiation of mousw fibroblasts into adipocytes. Mol Cell Biol,2004,24:8671-8680
[16]Huang C, Jacobson K, Schaller MD. MAP kinases and cell migration. J Cell Sci,2004,117:4619-4628
[17]Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol,1997,9:180-186
[18]Cano E, Mahadevan LC. Parallel signal processing among mammalian MAPKs. Trends Biochem Sci,1995,20:117-122
[19]Stains JP, Civitelli R. Gap junctions regulate extracellular signal-regulated kinase signaling to affect gene transcription. Mol Biol Cell,2005,16:64-72
[20]Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res,2005, 309:99-109
[21]Luo XH, Guo LJ, Xie H, et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts via the MAPK signaling pathway. J Bone Miner Res.2006,21:1648-1656.
[22]Pantouli E, Boehm MM, Koka S. Inflammatory cytokines activate P38 MAPK to incluce osteoprotegerin synthesis by MG-63 cells. Biochem Biophys. Res Commun,2005,329:224-229
[23]Seger R, Krebs EG. The MAPK signaling cascade. FASEB J,1995,9: 726-35
[24]Selvamurugan N, Kwok S, Alliston T, et al. Transforming Growth Factor-_1 Regulation of Collagenase-3 Expression in Osteoblastic Cells by Cross-talk between the Smad and MAPK Signaling Pathways and Their Components, Smad2 and Runx2. J Biol Chem,2004,279:19327-19334
[25]Blair HC, Robinson LJ, Zaidi M. Osteoclast signalling pathways.Biochem Biophys Res Commun,2005,328:728-38.
[26]Pantouli E, Boehm MM, Koka S.Inflammatory cytokines activate p38 MAPK to induce osteoprotegerin synthesis by MG-63 cells. Biochem Biophys Res Commun,2005,329:224-229
[27]Engelbrecht Y, de Wet H. Horsch K, et al. Glucocorticoids induce rapid up-regulation of mitogen-activated protein kinase phosphatase-1 and dephosph-orylation of extrcellular signal-regulated kinase and impair proliferation in human and mouse osteoblast cell lines. Endocrinology,2003,144:412-422
[28]Tsai KS, Yang RS, Liu SH. Benzoapyrene regulates osteoblast proliferation through an estrogen receptor-related cyclooxygenase-2 pathway.Chem Res Toxicol, 2004,17:679-684
[29]Arita Y, Kihara S, Quchi N, et al. Adipocyte-derived plasma protein, adiponectin, act as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation,2002,105:2893-2898
[30]Oqunwobi OO, Beales IL. Adiponectin stimulates proliferation and cytokine secretion in colonic epithelial cells. Requl Pept,2006,134:105-113
[31]Shibata R, Ouchi N, Ito M, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med,2004,10:1384-1389
[32]Noth U, Tuli R, Seghatoleslami R, et al. Activation of p38 and Smads mediates BMP-2 effects on human trabecular bone-derived osteoblasts, Exp Cell Res, 2003,291:201-211
[33]Gallea S, Lallemand F, Atfi A, et al. Activation of mitogen-activated protein kinase cascades is involved in regulation of bone morphogenetic protein-2-induced osteoblast differentiation in pluripotent C2C12 cells. Bone,2001,28:491-498
[34]Guicheux J, Lemonnier J, Ghayor C, et al. Activation of p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase by BMP-2 and their implication in the stimulation of osteoblastic cell differentiation. J Bone Miner Res, 2003,18:2060-2068
[35]Hu Y, Chan E, Wang SX, et al. Activation of p38 mitogen-activated protein kinase is required for osteoblast differentiation. Endocrinology,2003,144: 2068-2074.
[36]Kakita A, Suzuki A, Ono Y, et al. Possible involvement of p38 MAP kinase in prostaglandin El-induced ALP activity in osteoblast-like cells. Prostaglandins Leukot Essent Fatty Acids,2004,70:469-474
[37]Jono S, Nishizawa Y, Shioi A, et al. Paathyroid hormone-related peptide as a local regulater of vascular calcification:its inhibitony on in vitro calcification by bovine vascular smooth muscle cell. Arterioscler Thromb Vasc Biol,1997,17: 1135-1142
[38]Maahs DM, Ogden LG, Kinney GL, et al. Low plasma adiponectin levels predict progression of coronary artery calcification. Circulation,2005,111:747-753
[39]Kadowaki T, Yamauchi T, Kubota N, et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest, 2006,116:1784-1792
[40]Yatagai T, Nagasaka S, Taniguchi A, et al. Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus.Metabolism,2003,52:1274-1278
[41]Lindsay RS, Funahashi T, Hanson RL, et al. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet,2002,360:57-58
[42]Daimon M, Oizumi T, Saitoh T,et al. Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese Population:the Funagata study. Diabetes Care,2003,26:2015-2020
[43]Maeda N, Shimomural L. Kishida K et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30 Nature Med,2002,8:731-740
[44]Lenchik L, Register TC, Hsu FC, et al. Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone,2003,33:646-651
[45]Peng XD, Xie H, Zhao Q, et al. Relationships between serum adiponectin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in Chinese men. Clin Chim Acta,2008,387:31-35
[46]Son BK, Akishita M, Iijima K, et al. Adiponectin antagonizes stimulatory effect of TNFa on vascular smooth muscle cell calcification:regulation of Gas6-mediated survival pathway by AMP-activated protein kinase. Endocrinology, 2008. [Epub ahead of print].
[47]Yameuchi T, Hara K, Kabota, N, et al. Dual roles of adiponectin/acrp 30 in vivo as anti-atherogenic adipokine. Curr Drug Targets Immune Endari Metabol Disord,2003,3243-3254
[1]Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to C1q produced exclusively in adipocyte.J Biol Chem,1995,270:26746-26749
[2]Maeda K, Okubo K, Shimomural I, et al. cDNA clong and expression of a novel adipose specific collagen-like factor, apMl (Adipose Most abundant Gene transcript 1). Biochem Biophys Res Commun,1996,221:286-289
[3]Hu E, Liang P, Spieglman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Bio Chem,1996,271:10697-10703
[4]Nakano Y, Tobe T, Choi-Miura NH, et al. Isolation and characterization of GBP28,a novel gelatin-binding protein purified from human plasma. J Biochem, 1996,20:803-812
[5]Arita Y, Kihara S, Ouchi N, et al. Paradoxiclal decrease of an adipose-specific protein,adiponectin in obesity. Biochem Biophys Res Commun,1999,257:79-83
[6]Pajvani UB, Du X, Combs TP, et al. Structure-function studies of the adipoc yte-secreted hormone Acrp30/adiponectin implication for metabolic regulation and bioactivity. J Biol Chem,2003,278:9073-9085
[7]Kishida K, Nagaretani H, Kondo H, et al. Disturbed secretion of mutant adiponectin associated with the metabolic syndrome. Biochem Biophys Res Commun,2003,306:286-292
[8]Matasuzawa Y, Funahashi T, Kihara S, et al. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol,2004,24:29-33
[9]Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol,2003,23:85-89
[10]Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of family of soluble defense collagens,negatively regulates the grouth of myelomo-nocytic progenitors and the functions of macrophages. Blood,2000,96:1723-1732
[11]Ma K, Cabrero A, Saha PK, et al. Increased β-oxidation but no insulin resistance or glucose intolererance in mice lacking adiponectin. J Bio Chem, 2002,277:34658-34661
[12]Matsuda M, Shimonura I, Sata M, et al. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Bio Chem,2002, 277:37487-37491
[13]Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/Acrp30. Nat Med,2002,8:731-737
[14]Matsuzawa Y, Shimomura I, Kihara S, et al. Importance of adipocytokines in obesity-related diseases. Horm Res,2003,60 Suppl 3:56-59
[15]Satoh H, Audrey N, Trujillo M, et al. Adenovirus-mediated adiponectin expression augments akeletal muscle insulin sensitivity in male Wistar rats. Diabetes, 2005,54:1304-1313
[16]Ouchi N, Kihara S, Funashashi T, et al. Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol,2003,14:561-566
[17]Hotta K, Funahashi T, Bodkin NL, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes,2001, 50:1126-1133
[18]Yamauchi T, Hara K, Kubota N, et al. Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine. Curr Drug Targets Immune Endocr Metabol Disord,2003,4:243-254
[19]Kubota N, Terauchi Y, Yamauchi T, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Bio Chem,2002,277:25863-25866
[20]Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules:adipocyte-derived plasma protein adiponectin. Circulation,1999,100: 2473-2476
[21]Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein, adiponection suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation,2001,103:1057-1063
[22]Ouchi N, Kihara S, Funahashi T, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation,2003, 107:671-674
[23]Zietz B, Herfarth H, Paul G, et al. Adiponectin represents and independent cardiovascular risk factor predicting serum HDL-Cholesterol levels in type 2 diabetes. FFBS Lett,2003,545:103-104
[24]Teschritter O, Fritsche A, Thamer C, et al. Plasma adiponectin concentration predict insulin sensitivity of both glucose and lipid metabolism. Diabetes,2003, 52:239-243
[25]Hulthe J, Hulten LM, Fagerberg B. Low adipocyte-derived plasma protein adiponectin concentrations are associated with the metabolic syndrome and small dense low-density lipoprotein particles:Atherosclerosis and insulin resistance study. Metabolism,2003,52:1612-1614
[26]Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation,2000,102:1296-1301
[27]Okamoto Y, Arita Y, Nishida M, et al. An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res,2000,32:47-50
[28]Okamoto Y, Kihara S, Ouchi N, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation,2002,106:2767-2770
[29]Ouchi N, Ohishi M, Kihara S, et al. Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension,2003,42:231-234
[30]Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med,2002,8:1288-1295
[31]Pischon T, Girman CJ, Hotamisligil GS, et al. Plasma adiponectin levels and risk of myocardial infraction in men. Jama,2004,291:1730-1737
[32]Shibata R, Ouchi N, Ito M, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart.Nat Med,2004,10:1384-1389
[33]Liao Y, Takashima S, Maeda N, et al. Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism. Cardiovasc Res,2005,67:705-713
[34]Kato H, Kashiwagi H, Shiraga M, et al. Adiponectin acts as an endogenous antithrombotic factor. Arterioscler Thromb Vasc Biol,2006,26:224-230
[35]Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose-specific protein,adiponectin in obesity. Biochem Biophys Res Commun,1999,257: 79-83
[36]Xu A, Wang Y, Keshaw H, et al. The fat-derived hormone adiponectin alleviates alcholic and nonalcoholic fatty liver diseases in mice. J Clin Invest,2003, 112:91-100
[37]Yamauchi T, Kamon J, Ito Y, et al.loning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature,2003,423:762-769
[38]Musso G, Gsmbino R, Biroli G, et al. Hypoadiponectinemia predicts the severity of hepatic fibrosis and pancreatic Beta-cell dysfunction in nondiabetic nonobese patients with nonalcoholic steatohepatitis. Am J Gastroenterol,2005, 100:2438-2446
[39]Wolf AM, Wolf D, Avila MA, et al. Up-regulation of the anti-inflammatory adipokine adiponectin in acute liver failure in mice. J Hepatol,2006,44:537-543
[40]Masaki T, Chiba S, Tatsukawa H, et al. Adiponectin protects LPS-induced liver injury through modulation of TNF-alpha in KK-Ay obese mice. Hepatology, 2004,40:177-184
[41]Kamada Y, Tsmura S, Kiso S, et al. Enhanced carbon tetracholoride-induced liver fibrosis in mice lacking aiponectin. Gastroenterology,2003,125:1796-1807
[42]Matsumoto H, Tamura S, Kamada Y, et al. Adiponectin deficiency exacerbates lipopolysaccharide/D-galactosamine-induced liver injury in mice. World J Gastroenterol,2003,12:3352-3358
[43]Berner HS, Lyngstadaas SP, Spahr A, et. Al. Adiponectin and its receptors are expressed in bone-forming cells. Bone,2004,35:842-849
[44]Oshima K, Nampei A, Matsuda M, et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun,2005,331:520-526
[45]Shinoda Y, Yamaguchi M, Ogata N, et al. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell Biochem,2006,99:196-208
[1]Hutley L, Prins JB. Fat as endocrine organ:relationship to the metabolic syndrome1.Am J Med Sci,2005,330:2802-2891
[2]Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med,2004,350:2362-2374
[3]Matsuzawa Y. Adipocytokines and metabolic syndrome. Semin Vasc Med, 2005,5:34-39
[4]Rabin KR, Kamari Y, Avni I, et al. Adiponectin:linking the metabolic syndrome to its cardiovascular consequences. Expert Rev Cardiovasc Ther,2005,3: 465-471
[5]Guzik TJ, Korbut R, Adamek-Guzik T. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol,2003,54:469-487.
[6]Tilg H, Moschen AR. Adipocytokines:mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol,2006,6:772-783.
[7]Calabro P,Yeh ET. Obesity, inflammation, and vascular disease:the role of the adipose tissue as an endocrine organ. Subcell Biochem,2007,42:63-91
[8]Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation, 2002,105:1135-1143
[9]Trayhurn P, Wood IS. Signalling role of adipose tissue:adipo2 kines and inflammation in obesity. Biochem Soc Trans,2005,33:1078-1081
[10]Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med,1999, 340:115-126
[11]Verma S and Anderson TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation,2002,105:546-549
[12]Christiansen T, Richelsen B, Bruun JM. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int J Obes Relat Metab Disord,2005,29: 146-150
[13]Pelleymounter MA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science,1995,269:540-543
[14]Lee GH, Proenca R, Montez JM, et al. Abnormal splicing of the leptin receptor in diabetic mice.Nature,1996,379:632-635
[15]Saladin R, De Vos P, Guerre-Millo M, et al. Transient increase in obese gene expression after food intake or insulin administration. Nature,1995,377: 527-529
[16]Geffroy S, De Vos P, Staels B, Duban B, Auwerx J, de Martinville B. Localization of the human OB gene (OBS) to chromosome 7q32 by fluorescence in situ hybridization. Genomics,1995,28:603-604
[17]Zoladz JA, Konturek SJ, Duda K, et al. Effect of moder and ate incremental exercise, performed in fed and fasted state on cardio-respiratory variables leptin and ghrelin concentrations in young healthy men. J Physiol Pharmacol,2005,56:63-85
[18]Kaminski T, Smolinska N, Gajewska A, et al. Leptin and long form of leptin receptor genes expression in the hypothalamus and pituitary during the luteal phase and early pregnancy in pigs. J Physiol Pharmacol,2006,57:95-108
[19]Stallmeyer B, Pfeilschifter J, Frank S. Systemically and topically supplemented leptin fails to reconstitute a normal angiogenic response during skin repair in diabetic ob/ob mice. Diabetologia,2001,44:471-479
[20]Kougias P, Chai H, Lin PH, et al. Effects of adipocyte-derived cytokines on endothelial functions:implication of vascular disease. J Surg Res,2005,126:121-129
[21]Knudson JD, Dincer UD, Zhang C, et al. Leptin receptors are expressed in coronary arteries, and hyperleptnemia causes significant coronary endothelial dysfunction. Am J Physiol Heart Circ Physiol,2005,289:H48-H56
[22]Shek EW, Brands MW, Hall JE. Chronic leptin infusion increases arterial pressure. Hypertension,1998,31:409-414
[23]Galili O, Versari D, Sattler KJ, et al. Early Experimental Obesity Is Associated with Coronary Endothelial Dysfunction and Oxidative Stress. Am J Physiol Heart Circ Physiol,2006, electronic version.
[24]Guzik TJ, Sadowski J, Kapelak B, et al. Systemic regulation of vascular NAD(P)H oxidase activity and nox isoform expression in human arteries and veins. Arterioscler Thromb Vasc Biol,2004,24:1614-1620
[25]Mussa S, Guzik TJ, Black E, et al. Comparative efficacies and durations of action of phenoxybenzamine, verapamil/nitroglycerin solution, and papaverine as topical antispasmodics for radial artery coronary bypass grafting. J Thorac Cardiovasc Surg,2003.126:1798-1805
[26]Black EA, Guzik TJ, West NE, et al. Minimally invasive saphenous vein harvesting:effects on endothelial and smooth muscle function. Ann Thorac Surg.2001,71:1503-1507
[27]Barouch LA, Berkowitz DE, Harrison RW, et al. Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice1.Circulation,2003,108:754-759
[28]Rahmouni K, Morgan DA, Morgan GM, et al. Role of selective leptin resistance in diet induced obesity hypertension. Diabetes,2005,54:2012-2018
[29]Steppan CM, Bailey ST, Bhat S, et al. Hormone resistin links obesity to diabetes. Nature,2001,409:307-312.
[30]Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes1 Nature,2001,409:307-312
[31]Banerjee RR, Rangwala SM, Shapiro JS, et al. Regulation of fasted blood glucose by resistin. Science,2004,303:1195-1198
[32]Jung HS, Park KH, Cho YM, et al. Resistin is secreted from macrophages in atheromas and promotes atherosclerosis. Cardiovas Res,2006,69:76-85
[33]Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to C1q produced exclusively in adipocyte.J Biol Chem,1995,270:26746-26749
[34]Maeda K, Okubo K, Shimomural I, et al. cDNA clong and expression of a novel adipose specific collagen-like factor, apMl (Adipose Most abundant Gene transcript 1). Biochem Biophys Res Commun,1996,221:286-289
[35]Hu E, Liang P, Spieglman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Bio Chem,1996,271:10697-10703
[36]Nakano Y, Tobe T, Choi-Miura NH, et al. Isolation and characterization of GBP28,a novel gelatin-binding protein purified from human plasma. J Biochem, 1996,20:803-812
[37]Pajvani UB, Du X, Combs TP, et al. Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. J Biol Chem,2003,278:9073-9085
[38]Shapiro L, Scherer PE. The crystal structure of a complement-lq family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol,1998,8: 335-338
[39]Tsao TS, Murrey HE, Hug C, et al. Oligomerization state-dependent activation of NF-kappa B signaling pathway by adipocyte complement-related protein of 30 kDa (Acrp30). J Biol Chem,2002,277:359-362
[40]Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature,2003,423:762-769
[41]Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev,2005,26:439-451
[42]Ouchi N, Kihara S, Arita Y. Novel modulator for endothelial adhesion molecules:adipocyte-derived plasma protein adiponectin. Circulation.1999,100: 2473-2476
[43]Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kB signaling through a cAMP dependent pathway. Circulation,2000,102:1296-1301
[44]Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood,2000,96: 1723-1732
[45]Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation,2001,103:1057-1063
[46]Yamauchi T, Kamon J, Waki H, et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem,2003, 278:2461-2468
[47]Okamoto Y, Kihara S, Ouchi N, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation,2002,106(22):2767-2770
[48]Matsuda M, Shimomura I, Sata M, et al. Role of adiponectin in preventing vascular stenosis-the missing link of adipo-vascular axis. J Biol Chem,2002,277: 37487-37491
[49]Arita Y, Kihara S, Quchi N, et al. Adipocyte-derived plasma protein, adiponectin, act as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation,2002,105:2893-2898
[50]Paukac L, Huanqpu J, Karnovsky MJ. Platelet-derived growth factor-BB, insulin-like growth factor-1, and phorbol ester activate different signaling pathways for stimulation of vascular smooth muscle cell migration. Exp Cell Res,1998,242: 548-560
[51]Chen H, Montagnani M, Funahashi T, et al. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem,2003,278 21-26
[52]Shibata R, Ouchi N, Ito M, et al.Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med,2004,10:1384-1389
[53]Shibata R, Sato K, Pimentel DR, et al.Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK-and COX-2-dependent mechanisms.Nat Med,2005,11:1096-1103
[54]Fukuhara A, Mat suda M, Nishizawa M, et al. Visfatin:a protein secreted by visceral fat t hat mimics t he effect s of insulin.Science,2005,307:426-430
[55]Samal B, Sun Y, Stearns G, et al. Cloning and characterization of t he cDNA encoding a Novel Human Pre2B2 cell colony enhancing factor. Mol Cell Biol, 1994,14:1431-1437
[56]Ognjanovic S, Bao S, Yamamoto SY, et al. Genomic organization of the gene coding for human pre2B2cell colony enhancing factor and expression in human fetal membranes. J Mol Endo crinol,2001,26:107-117
[57]van der Veer E, Nong Z, O'Neil C, et al. Pre2B2cell colony enhancing factor regulates NAD+dependent protein deacetylase activity and promotes vascular smoot h muscle cell maturation.Circ Res,2005,97:25-34
[58]Kralisch S,Klein J,Lossner U,et al. Hormonal regulation of the novel adipocytokine visfatin in 3T3-LI adipocytes. J endocrinol,2005,185:R1-R8.
[59]Hug C, Lodish HF. Medicine. Visfatin:a new adipokine[J]. Science.2005, 307:366-367
[60]Jia SH, Li Y, Parodo J, et al. Pre2B cell colony enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis [J]. J Clin Invest,2005,113:1318-1327.
[61]van de Veer E, Nong Z, O'Neil C, et al. Pre2B2cell colony enhancing factor regulates NAD+2dependent protein deacety lase activity and promotes vascular smooth muscle cell maturation. Circ Res,2005,97:25-34.
[62]O'Dowd BF,Heiber M,Chan A, et al. A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene, 1993,136:355-360
[63]Tatemoto K,Hosoya M,Habata Y, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor.Biochem Biophys Res Commun,1998.251:471-476.
[64]Szokodi I, Tavi P, Foldes G, et al. Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility. Circ Res,2002,91:434-440
[65]Zhong JC, Huang DY, Liu GF, et al. Effects of all-trans retinoic acid on orphan receptor APJ signaling in spontaneously hypertensive rats. Cardiovasc Res,2005,65:743-750
[66]Lee DK, Cheng R, Nguyen T, et al. Characterization of apelin, the ligand for the APJ receptor. J Neurochem.2000,74:34-41
[67]Tatemoto K, Takayama K, Zou MX, et al. The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism. Regul Pept,2001,99:87-92
[68]Cheng X, Cheng XS, Pang CC. Venous dilator effect of Apelin, an endogenous peptide ligand for orphan APJ receptor, in conscious rats. Eur J Pharm acol,2003,470:171-175
[69]Ashley EA, Powers J,Chen M, et al. The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo Cardiovasc Res,2005,65:73-82.
[70]Chen MM, Ashley EA, Deng DX, et al. Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction. Circulation,2003, 108:1432-1439
[71]Foldes G, Horkay F, Szokodi I, et al. Circulating and cardiac levels of Apelin, the novel ligand of the orphan recep tor APJ, in patients with heart failure. Biochem Biophys Res Commun,2003,308:480-485
[72]Sonnenberg GE, Krakower GR, Kissebah AH1 A novel pathway to the manifestations of metabolic syndrome. Obes Res,2004,12:180-186
[73]Hutley L, Prins JB. Fat as endocrine organ:relationship to the metabolic syndrome. Am J Med Sci,2005,330:280-289
[74]Vincenzo P, James T. Willerson. Direct proinflammatory effect of C-reactive protein on human endothelial cells.Circulation,2000,102:2165-2168
[75]Klein J, Perwitz N, Kraus D, et al. Adipose tissue as source and target for novel therapies. Trends Endocrinol Metab,2006,17:26-32
[2]Jono S, NisbizawaY, Shioi A, etal.1.25-Dihydroxyvitam in D3 increases in vitro vascular calcification by modulating secretion of endogenous parathyroid hormone-related peptide. Circulation,1998,98:1302-1306
[3]Chen NX, Moe SM. Arterial Calcification in diabetes. C URR Diab Rep, 2003,3:28-32
[4]Johnson RC, Leopold JA. Loscalzo J. vascular calcification pathobiological mechanisms anol clinical implications, Circ Res,2006,99:1044-1059
[5]Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to C1q produced exclusively in adipocyte J Biol Chem,1995,270:26746-26749
[6]Maeda K, Okubo K, Shimomural I, et al. cDNA clong and expression of a novel adipose specific collagen-like factor, apMl (Adipose Most abundant Gene transcript 1). Biochem Biophys Res Commun,1996,221:286-289
[7]Hu E, Liang P, Spieglman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Bio Chem,1996,271:10697-10703
[8]Nakano Y, Tobe T, Choi-Miura NH, et al. Isolation and characterization of GBP28,a novel gelatin-binding protein purified from human plasma. J Biochem,1996;20:803-812
[9]Arita Y, Kihara S, Ouchi N, et al. Paradoxiclal decrease of an adipose-specific protein,adiponectin in obesity. Biochem Biophys Res Commun,1999,257:79-83
[10]Pajvani UB, Du X, Combs TP, et al. Structure-function studies of the adipoc yte-secreted hormone Acrp30/adiponectin implication for metabolic regulation and bioactivity. J Biol Chem,2003,278:9073-9085
[11]Kishida K, Nagaretani H, Kondo H, et al. Disturbed secretion of mutant adiponectin associated with the metabolic syndrome. Biochem Biophys Res Commun,2003,306:286-292
[12]Kadowaki T and Yamauchi T. Adiponectin and diponectin receptors Enaloerine Reviews,2005,26:439-451
[13]Hotta K, Funahashi T, Bodkin NL. etal. Circulating concentrations of the adipocyte protein adiponectin are decreased in paralkl with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkey. Diabetes,2001,50: 1126-1133
[14]Gracheli CM.Vadcular calcification mechanisms. J Am Soc Nephrol, 2004,15:2959-2964
[1]Francke S. ManraiM, Lacquemant C, et al. A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on Chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q 27. Hum Md Genet, 2011,10:2751-2765
[2]Viooonet N, Hani EH, Dupnt S, et al. Genome-wide search for type 2 diabetes-susceptibility genes in French whites, evidence for a novel susceptibility locus for early-onset diabetes on Chromosome 3q27-gter and independent replication of type 2 diabetes locus on Chromosome 1q21-q24. Am J Hum Genet,2000, 67:1470-1480
[3]Harak, Boutin P, Mori Y, et al. Genetic variation in the gene encoding adiponectin is associated with an increased risk of Type 2 diabetes in the Japanese population. Diabetes,2002,51:536-540
[4]Spranger J. Kroke A. Mohlig M et al. Adiponectin and protection against type 2 diabetes mellitus. Lancet,2003,361:226-228
[5]Hota K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel adipose-specific protein adiponectin in type 2 deabetic patients. Arterioscler Thromb vasc Biol,2000,20:1595-1599
[6]任维华,李西华,王芳等.Adiponectin基因剔除LacZ基因敲入小鼠模型的建立。生物化学与生物物理进展,2006,33：846-853
[7]Kemedy AR, Pissios P, Otu H, et al. A high-fat ketogenic diet induces a unique metabolic state in mice. Am J Physiol Endocrinol Metab,2007.292: E1724-1739
[8]Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to C1q produced exclusively in adipocyte.J Biol Chem,1995,270:26746-26749
[9]Maeda K, Okubo K, Shimomural I, et al. cDNA clong and expression of a novel adipose specific collagen-like factor, apMl (Adipose Most abundant Gene transcript 1). Biochem Biophys Res Commun,1996,221:286-289
[10]Hu E, Liang P, Spieglman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Bio Chem,1996,271:10697-10703
[11]Nakano Y, Tobe T, Choi-Miura NH, et al. Isolation and characterization of GBP28,a novel gelatin-binding protein purified from human plasma. J Biochem, 1996,20:803-812
[12]Matsuzawa Y, Shimomura I, Kihara S, et al. Importance of adipocytokines in obesity-related diseases. Horm Res,2003,60 Suppl 3:56-59
[13]Satoh H, Audrey N, Trujillo M, et al. Adenovirus-mediated adiponectin expression augments akeletal muscle insulin sensitivity in male Wistar rats. Diabetes, 2005,54:1304-1313
[14]Ouchi N, Kihara S, Funashashi T, et al. Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol.2003,14:561-566
[15]Hotta K, Funahashi T, Bodkin NL, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes,2001, 50:1126-1133
[16]Yamauchi T, Hara K, Kubota N, et al. Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine. Curr Drug Targets Immune Endocr Metabol Disord,2003:243-254
[17]Parhami F, Tintut Y, Patel JK et al. Regulation of vascular Calcification in atherosclerosis. Z. karadiol,2001,90:27-30
[18]Wallin R, Wajih N, Green wood GT, et al, Arterial Calcification:a review of mechanisms, animal models and the prospects for therapy. Med Res Rev,2001, 21:274-301
[19]Matasuzawa Y, Funahashi T, Kihara S, et al. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol,2004,24:29-33
[20]Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadipo-nectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol, 2003,23:85-89
[21]Maahs DM,Ogden LG, Kinney GL et al. Low plasma adiponatin levels predict progress of coronary artery calcification. Circulation,2005,116:747-753
[22]Steffes MW, Gross MD, Lee DH, et al. Adiponectin, visceral fat, oxidative stress, and early macrovascular diaease:the coronary artery risk development in young adults study. Obesity,2006,14:319-326
[23]Im JA, Kim SH, Lee JW, et al. Association between hypoadiponectinemia and cardiovascular risk factors in nonobese healthy adults. Metabolism,2006,55: 1546-1550
[24]Kim OY, Koh SJ, Jang Y, et al. Plasma adiponectin is related to other cardiovascular risk factors in nondiabetic Korean men with CAD, independent of adiposity and cigarette smoking:cross-sectional analysis. Clin Chim Acta,2006,370: 63-71
[25]Chen MP, Tsai JC, Chung FM, et al. Hypoadiponectinemia is associated with ischemic cerebrovascular disease. Arterioscler Thromb Vasc Biol,2005,25: 821-826
[26]Dunajska K, Milewicz A, Jedrzejuk D, et al. Plasma adiponectin concentration in relation to severity of coronary atherosclerosis and carkiovascular risk factors in middle-aged men. Endocrine,2004,25:215-221
[27]Ouchi N, Kihara S, Funahashi T, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation, 2003,107:671-674
[28]Zietz B, Herfarth H, Paul G, et al. Adiponectin represents and independent cardiovascular risk factor predicting serum HDL-Cholesterol levels in type 2 diabetes. FFBS Lett,2003,545:103-104
[29]Teschritter O, Fritsche A, Thamer C, et al. Plasma adiponectin concentration predict insulin sensitivity of both glucose and lipid metabolism. Diabetes,2003, 52:239-243
[30]Hulthe J, Hulten LM, Fagerberg B. Low adipocyte-derived plasma protein adiponectin concentrations are associated with the metabolic syndrome and small dense low-density lipoprotein particles:Atherosclerosis and insulin resistance study. Metabolism,2003,52:1612-1614
[31]姚君厘.糖尿病和大血管病变.上海医药,2006,27：253-256
[32]Johnson RC, Leopold JA, Loscalzo J. Vascular calcification pathobiological mechanisms and clinical implications. Circ. Res,2006,99:1044-1059
[33]Chen NX, Moe SM. Arterial calcification in diabetes. Current Diabetes Reports,2003,3:28-32
[34]Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocrine Reviews,2005,26:439-451
[35]Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab,2004,89:2548-2556
[36]刘亚平,季虹,荣海欣等.2型糖尿病雌性大鼠骨代谢的特点.中国骨质疏松杂志,2008,14：35-38
[37]何清华,周迎生,王征等.2型糖尿病模型制备的影响因素及其特点.中国实验动物学报,2007,15：425-429
[38]余传林,朱正光,雷林生等.链脲佐菌素糖尿病模型动物血糖及体征动态变化的研究.南方医科大学学报,2008,28：132-133
[39]吴胜英,潘春不,齐永芬等.雌激素减轻大鼠血管钙化的实验研究.郧阳医学院学报,2004,23：328-331
[40]Hoshi K, Ejiri S. Ozawa H. Localizational alterations of calcium, phosphorus and calcificating-related organics such as proteoglycans and alkaline phosphatase during bone calcification. J Bone Miner Res,2001,16:289-298
[41]Shioo A. Nishizawa Y, Jono S, et al. β-Glycerohosphate calcification in cultured bovine vascular smooth muscle cells. Arterioscler Thromb vasc Biol, 1995,15:2003-2009
[42]Proudfoot D, Skepper JN, Shanahan CM, et al. Calcification of human vascular cells in vitro is correlated with high levels of matrix Glaprotein and low levels of osteopontin expression. Arterioscler Thromb vasc Biol,1998,18:379-388
[43]Wennberg C, Hessle L, Lundberg P, et al. Functional Characterization of osteoblasts and osteoclasts from alkaline phosphatase knaeout mice. J. Bone Miner Res,2000,15:1879-1888
[44]Stock M. otto F. Control of Runx2 isoform espression:the role of promoters and enhancers J Cell Biochem,2005,95:506-517
[45]Enomoto H, Furuichi T, Zanma A, et al. Runx2 deficiency in chondrocytes causes adipogenic changes in vitro. J Cell Sci,2004,117:417-425
[46]Gersbach CA, Byersb A, Pavlath GK,et al. Runx2/CBFα1 stimulates trans differentiation of primary skeletal myoblasts into a mineralizing osteoblastic phentype. Exp cell Res,2004,300:406-417
[47]Chen NX, Duan D, ONeil KD, et al. High glucose increases the expression of cbfal and BMP-2 and enhances the calcification of vasculan smooth muscle cells. Nephrol Dial Transplant,2006,21:3435-3442
[1]ketteler M, Giachellic. Novel insights into vascular calcification. kidney Int. Suppl,2006,105:s5-9
[2]Johnson RC, Leopold JA, Loscalzo J. Vascular calcification pathobiological mechanisms and clinical implications. Circ Res,2006,99:1044-1059
[3]Giachelli CM. Vascular calcification mechanisms.J Am Soc Nephrol.2004, 15:2959-2964
[4]Yamauchi I, Kamon I, Iro Y et al.Cloning of adiponectin receptors that mediate antidiabetic metabolic cffects.Narure,2003,423:762-769
[5]Civitarese AE,Jenkinson CP,Richardson D,et al.Adiponectin receptors gene expression and insulin sensitivity in non-diabetic Mexican Amerivan with or without a family history of Type 2 diabetes.Diabetologia,2004,47:816-820
[6]Berner HS, Lyngstadaas SP, Spahr A,et al. Adiponectin and its receptors are expressed in bone-forming cells. Bone,2004,35:842-849
[7]Luo XH, Guo LJ, Yuan LQ et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res,2005, 309:99-109
[8]Luo XH, Guo LJ, Xie H et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts via the MAPK signaling pathway. J Bone Miner Res,2006,21:1648-1656
[9]Parhami F,Tintut T,Patel JK, et al. Regulation of vascular calcification in atherosclerosis Z kardiol,2001,90:27-30
[10]Cozzolino M, Dusso AS, Slatopolsky E. Role of calcium-phosphate product and bone-associated proteins on vascular calcification in renal failure. J Am Soc Nephrol,2001,12:2511-2516
[11]Chen NX, Duan D, Moe SM, et al. High glucose increases the expression of Cbfa1 and BMP-2 and enhances the calcification of vascular smooth muscle cells. Nephrol Dial Transplant,2006,21:3435-3442
[12]Ding HT, Wang CG, Zhang TL, et al. Fibronectin enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells via ERK pathway. J Cell Biochem,2006,99:1343-1352
[13]Simionescu A, Philips K, Vyavahare N. Elastin-derived peptides and TGF-betal induce osteogenic response in smooth muscle cells. Biochem Biophys Res Commun.2005,334:524-532
[14]Campbell GR,Campbell JH. Vascular smooth muscle and arterial calcification. Z Kardiol,2000,89:254-262
[15]Steitz SA, Speer MY, Curinga G, et al. Smooth muscle cell phenotypic transition associated with calcification-Upregulation of Cbfal and downregulation of smooth muscle lineage markers. Circ Res,2001,89:1147-1154
[16]Kobayashi R, Kubota T, Hidaka H, et al. Purification, characterization, and partial sequence analysis of a new 25-kDa actin binding protein from bovine aorta:a SM22 homologue. Biochem Biophys Res Commun,1994,198:1275-1280
[17]Matasuzawa Y, Funahashi T, Kihara S, et al. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol,2004,24:29-33
[18]Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadipo-nectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol,2003, 23:85-89
[19]Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of family of soluble defense collagens,negatively regulates the grouth of myelom-onocytic progenitors and the functions of macrophages. Blood,2000,96:1723-1732
[20]Kadowaki T, Yanauchi T.Adiponectin and adiponectin receptors.Endocr Rev 2005,26:439-451
[21]Shioi A, NishizawaY,Jono S, et al. B-Glycerophosphate accelerates calcification in culture bovine vascular smooth muscle cells.Arterioscler Thromb Vasc Biol,1995,15:2003-2009
[22]Proudfoot D, Skepper JN, Shanahan CM, et al. Calcification of human vascular ceoos in vitro is correlated with high levels of matris Glaprotein and Low levels of osteopontin expresion.Arterioscler Thromb Vasc Bid,1998,18:379-388
[23]Bellows CG, Aubin JE, Heersche JN.Initiation and progression of minerolization of bone nodules formal in vitro:the role of alkaline phosphatase and organic phosphate. Bone Mier,1991,14:27-40
[24]Gundberg CM. Biochemical markers of bone formation. Clin Lab Med, 2000,20:489-501
[25]Chen NX, Duan D, Moe SM, et al. High glucose increases the expression of Cbfal and BMP-2 and enhances the calcification of vascular smooth muscle cells. Nephrol Dial Transplant,2006,21:3435-3442
[26]Ding HT, Wang CG, Zhang TL, et al. Fibronectin enhances in vitro vascular calcification by promoting osteoblastic differentiation of vascular smooth muscle cells via ERK pathway. J Cell Biochem,2006,99:1343-1352
[27]王宇政,王土雯,佟万仁等.TGF-B对血管钙化的影响.心脏杂志,2001,13：170-172
[28]KomoRi T.Regulation of skeletao development by the Runx family of transcription factors. J cell Biochem,2005,95:445-453
[29]Nman ck. Shore P. the osteoblast transcription factor RunX2 is expressed in mammary epitheliao ceoos and mediates osteopontin expression. J Biol Chen,2003, 278:684-689
[30]Giachell CM. Ectopic Calcification:new concepts in cellular regulation. Z kardiol,200190:31-37
[31]Watson KE, Parhami F, Shin V, et al. Fibronectin and collagen I matrixes promote calcification of vascular cells in vitro, whereas collagen IV matrix is inhibitory. Arterioscler Thromb vasc Biol,1998,18:1964-1971
[32]Shioi A, Nishizawa Y, Jono S, et al. β-Glycerophosphate accelerates calcification in cultured bovine vascular smooth muscle cells. Arterioscler Thromb Vasc Biol,1995,15:2003-2009
[33]Yang H, Curinga G, Giachelli CM. Elevated extracellular calcium levels induce smooth muscle cell matrix mineralization in vitro. Kidney Int,2004,66: 2293-2299
[34]Jono S, McKee MD, Murry CE, et al. Phosphate regulation of vascular smooth muscle cell calcification. Circ Res,2000,87:e10-e17
[35]Sowa H, Kaji H, Yamaguchi T, et al. Smad3 promotes alkaline phosphatase activity and mineralization of osteoblastic MC3T3-E1 cells. J Bone Miner Res,2002, 17:1190-1199
[36]Noth U, Tuli R, Seghatoleslami R, et al. Activation of p38 and Smads mediates BMP-2 effects on human trabecular bone-derived osteoblasts, Exp Cell Res, 2003,291:201-211
[37]Yang S, Wei D, Wang D, et al. In vitro and in vivo synergistic interactions between the Runx2/Cbfal transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation. J Bone Miner Res,2003,18:705-715.
[1]Berner HS, Lyngstadoas SP, Spahr A, et al. Adiponectin and its receptors are expressed in bone forming cells. Bone,2004,35:842-849
[2]Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res,2005, 309:99-109
[3]Johnson RC, Leopold JA, Loscalzo J. Vascular calcification pathobiological mechanisms and clinical implications. Circ Res,2006,99:1044-1059
[4]Chen NX and Moe SM. Arterial calcification in diabetes. Current Diabetes Reports,2003,3:28-32
[5]Yamauchi T, Kamon J, Ito Y, et al. Cloning of Adiponectin receptors that mediate antidiabetic metabolce effects. Nature,2003,423:762-769
[6]Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both liporatrophy and obesity. Natl Med, 2001,7:941-946
[7]Weyer C, Funahash T, Tanaka S, et al. Hypoadiponectinemia in obesity and type 2 diabetes close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab,2001,86:1930-1935
[8]Yameuchi T, Hara K, Kabota N, et al. Dual roles of adiponectin/acrp30 in vivo as an anti-atherogenic adipokine. Curr Drug Targets Immune Endocri Metabol Disord,2003,3:243-254
[9]Wang H, Zhang HL, Jia YW, et al. Adiponectin receptors I gene (adipoR I) as a candidate for type 2 diabetes and insulin resistance. Diabetes,2004,53: 2132-2136
[10]Inukai K, Nakashima Y, Watanabe M, et al. Regulation of adiponectin receptor gene expression in diabetic mice. Am J Physiol Endocrnol Mctab,2005, 288:876-882
[11]Civitarese AE, Jenkinson CP, Richardson D, et al. Adiponectin receptors gene expression and insulin sensitivity in mon-diabetic Mexican American with or without a family history of type 2 diabetes. Diabetologia,2004,47:816-820
[12]Yamauchi T, Kamon J, Waki H, et al. Globular adiponectin protected ob/ob mice fromdiabetes and apoE deficient mice from atherosclerosis. J Bid Chem, 2003,278:2461-2468
[13]Gallea S, Lallemand F, Atfi A, et al. Activation of mitogen-activatec protein kinase cascades is involved in regulation of bone morphogenetic protein-2-induced osteoblast differentiation in pluripotent C2C12 cells. Bone,2001,5:491-498
[14]Celil AB, Campbell PG. BMP-2 and Insulin-like Growth Factor-I Mediate Osterix (Osx) Expression in Human Mesenchymal Stem Cells via the MAPK and Protein Kinase D Signaling Pathways. J Biol Chem,2005,36:31353-31359
[15]Park BH, Qiang L, Farmer SR. Phosphorylation of C/EBPβat a consensus extracellular signal-regulated kinase/glycogen synthase kinase 3 site is required for the adiponectin gene expression during the differentiation of mousw fibroblasts into adipocytes. Mol Cell Biol,2004,24:8671-8680
[16]Huang C, Jacobson K, Schaller MD. MAP kinases and cell migration. J Cell Sci,2004,117:4619-4628
[17]Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol,1997,9:180-186
[18]Cano E, Mahadevan LC. Parallel signal processing among mammalian MAPKs. Trends Biochem Sci,1995,20:117-122
[19]Stains JP, Civitelli R. Gap junctions regulate extracellular signal-regulated kinase signaling to affect gene transcription. Mol Biol Cell,2005,16:64-72
[20]Luo XH, Guo LJ, Yuan LQ, et al. Adiponectin stimulates human osteoblasts proliferation and differentiation via the MAPK signaling pathway. Exp Cell Res,2005, 309:99-109
[21]Luo XH, Guo LJ, Xie H, et al. Adiponectin stimulates RANKL and inhibits OPG expression in human osteoblasts via the MAPK signaling pathway. J Bone Miner Res.2006,21:1648-1656.
[22]Pantouli E, Boehm MM, Koka S. Inflammatory cytokines activate P38 MAPK to incluce osteoprotegerin synthesis by MG-63 cells. Biochem Biophys. Res Commun,2005,329:224-229
[23]Seger R, Krebs EG. The MAPK signaling cascade. FASEB J,1995,9: 726-35
[24]Selvamurugan N, Kwok S, Alliston T, et al. Transforming Growth Factor-_1 Regulation of Collagenase-3 Expression in Osteoblastic Cells by Cross-talk between the Smad and MAPK Signaling Pathways and Their Components, Smad2 and Runx2. J Biol Chem,2004,279:19327-19334
[25]Blair HC, Robinson LJ, Zaidi M. Osteoclast signalling pathways.Biochem Biophys Res Commun,2005,328:728-38.
[26]Pantouli E, Boehm MM, Koka S.Inflammatory cytokines activate p38 MAPK to induce osteoprotegerin synthesis by MG-63 cells. Biochem Biophys Res Commun,2005,329:224-229
[27]Engelbrecht Y, de Wet H. Horsch K, et al. Glucocorticoids induce rapid up-regulation of mitogen-activated protein kinase phosphatase-1 and dephosph-orylation of extrcellular signal-regulated kinase and impair proliferation in human and mouse osteoblast cell lines. Endocrinology,2003,144:412-422
[28]Tsai KS, Yang RS, Liu SH. Benzoapyrene regulates osteoblast proliferation through an estrogen receptor-related cyclooxygenase-2 pathway.Chem Res Toxicol, 2004,17:679-684
[29]Arita Y, Kihara S, Quchi N, et al. Adipocyte-derived plasma protein, adiponectin, act as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation,2002,105:2893-2898
[30]Oqunwobi OO, Beales IL. Adiponectin stimulates proliferation and cytokine secretion in colonic epithelial cells. Requl Pept,2006,134:105-113
[31]Shibata R, Ouchi N, Ito M, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med,2004,10:1384-1389
[32]Noth U, Tuli R, Seghatoleslami R, et al. Activation of p38 and Smads mediates BMP-2 effects on human trabecular bone-derived osteoblasts, Exp Cell Res, 2003,291:201-211
[33]Gallea S, Lallemand F, Atfi A, et al. Activation of mitogen-activated protein kinase cascades is involved in regulation of bone morphogenetic protein-2-induced osteoblast differentiation in pluripotent C2C12 cells. Bone,2001,28:491-498
[34]Guicheux J, Lemonnier J, Ghayor C, et al. Activation of p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase by BMP-2 and their implication in the stimulation of osteoblastic cell differentiation. J Bone Miner Res, 2003,18:2060-2068
[35]Hu Y, Chan E, Wang SX, et al. Activation of p38 mitogen-activated protein kinase is required for osteoblast differentiation. Endocrinology,2003,144: 2068-2074.
[36]Kakita A, Suzuki A, Ono Y, et al. Possible involvement of p38 MAP kinase in prostaglandin El-induced ALP activity in osteoblast-like cells. Prostaglandins Leukot Essent Fatty Acids,2004,70:469-474
[37]Jono S, Nishizawa Y, Shioi A, et al. Paathyroid hormone-related peptide as a local regulater of vascular calcification:its inhibitony on in vitro calcification by bovine vascular smooth muscle cell. Arterioscler Thromb Vasc Biol,1997,17: 1135-1142
[38]Maahs DM, Ogden LG, Kinney GL, et al. Low plasma adiponectin levels predict progression of coronary artery calcification. Circulation,2005,111:747-753
[39]Kadowaki T, Yamauchi T, Kubota N, et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest, 2006,116:1784-1792
[40]Yatagai T, Nagasaka S, Taniguchi A, et al. Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus.Metabolism,2003,52:1274-1278
[41]Lindsay RS, Funahashi T, Hanson RL, et al. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet,2002,360:57-58
[42]Daimon M, Oizumi T, Saitoh T,et al. Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese Population:the Funagata study. Diabetes Care,2003,26:2015-2020
[43]Maeda N, Shimomural L. Kishida K et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30 Nature Med,2002,8:731-740
[44]Lenchik L, Register TC, Hsu FC, et al. Adiponectin as a novel determinant of bone mineral density and visceral fat. Bone,2003,33:646-651
[45]Peng XD, Xie H, Zhao Q, et al. Relationships between serum adiponectin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in Chinese men. Clin Chim Acta,2008,387:31-35
[46]Son BK, Akishita M, Iijima K, et al. Adiponectin antagonizes stimulatory effect of TNFa on vascular smooth muscle cell calcification:regulation of Gas6-mediated survival pathway by AMP-activated protein kinase. Endocrinology, 2008. [Epub ahead of print].
[47]Yameuchi T, Hara K, Kabota, N, et al. Dual roles of adiponectin/acrp 30 in vivo as anti-atherogenic adipokine. Curr Drug Targets Immune Endari Metabol Disord,2003,3243-3254
[1]Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to C1q produced exclusively in adipocyte.J Biol Chem,1995,270:26746-26749
[2]Maeda K, Okubo K, Shimomural I, et al. cDNA clong and expression of a novel adipose specific collagen-like factor, apMl (Adipose Most abundant Gene transcript 1). Biochem Biophys Res Commun,1996,221:286-289
[3]Hu E, Liang P, Spieglman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Bio Chem,1996,271:10697-10703
[4]Nakano Y, Tobe T, Choi-Miura NH, et al. Isolation and characterization of GBP28,a novel gelatin-binding protein purified from human plasma. J Biochem, 1996,20:803-812
[5]Arita Y, Kihara S, Ouchi N, et al. Paradoxiclal decrease of an adipose-specific protein,adiponectin in obesity. Biochem Biophys Res Commun,1999,257:79-83
[6]Pajvani UB, Du X, Combs TP, et al. Structure-function studies of the adipoc yte-secreted hormone Acrp30/adiponectin implication for metabolic regulation and bioactivity. J Biol Chem,2003,278:9073-9085
[7]Kishida K, Nagaretani H, Kondo H, et al. Disturbed secretion of mutant adiponectin associated with the metabolic syndrome. Biochem Biophys Res Commun,2003,306:286-292
[8]Matasuzawa Y, Funahashi T, Kihara S, et al. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol,2004,24:29-33
[9]Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol,2003,23:85-89
[10]Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of family of soluble defense collagens,negatively regulates the grouth of myelomo-nocytic progenitors and the functions of macrophages. Blood,2000,96:1723-1732
[11]Ma K, Cabrero A, Saha PK, et al. Increased β-oxidation but no insulin resistance or glucose intolererance in mice lacking adiponectin. J Bio Chem, 2002,277:34658-34661
[12]Matsuda M, Shimonura I, Sata M, et al. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Bio Chem,2002, 277:37487-37491
[13]Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/Acrp30. Nat Med,2002,8:731-737
[14]Matsuzawa Y, Shimomura I, Kihara S, et al. Importance of adipocytokines in obesity-related diseases. Horm Res,2003,60 Suppl 3:56-59
[15]Satoh H, Audrey N, Trujillo M, et al. Adenovirus-mediated adiponectin expression augments akeletal muscle insulin sensitivity in male Wistar rats. Diabetes, 2005,54:1304-1313
[16]Ouchi N, Kihara S, Funashashi T, et al. Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol,2003,14:561-566
[17]Hotta K, Funahashi T, Bodkin NL, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes,2001, 50:1126-1133
[18]Yamauchi T, Hara K, Kubota N, et al. Dual roles of adiponectin/Acrp30 in vivo as an anti-diabetic and anti-atherogenic adipokine. Curr Drug Targets Immune Endocr Metabol Disord,2003,4:243-254
[19]Kubota N, Terauchi Y, Yamauchi T, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Bio Chem,2002,277:25863-25866
[20]Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules:adipocyte-derived plasma protein adiponectin. Circulation,1999,100: 2473-2476
[21]Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein, adiponection suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation,2001,103:1057-1063
[22]Ouchi N, Kihara S, Funahashi T, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation,2003, 107:671-674
[23]Zietz B, Herfarth H, Paul G, et al. Adiponectin represents and independent cardiovascular risk factor predicting serum HDL-Cholesterol levels in type 2 diabetes. FFBS Lett,2003,545:103-104
[24]Teschritter O, Fritsche A, Thamer C, et al. Plasma adiponectin concentration predict insulin sensitivity of both glucose and lipid metabolism. Diabetes,2003, 52:239-243
[25]Hulthe J, Hulten LM, Fagerberg B. Low adipocyte-derived plasma protein adiponectin concentrations are associated with the metabolic syndrome and small dense low-density lipoprotein particles:Atherosclerosis and insulin resistance study. Metabolism,2003,52:1612-1614
[26]Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation,2000,102:1296-1301
[27]Okamoto Y, Arita Y, Nishida M, et al. An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res,2000,32:47-50
[28]Okamoto Y, Kihara S, Ouchi N, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation,2002,106:2767-2770
[29]Ouchi N, Ohishi M, Kihara S, et al. Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension,2003,42:231-234
[30]Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med,2002,8:1288-1295
[31]Pischon T, Girman CJ, Hotamisligil GS, et al. Plasma adiponectin levels and risk of myocardial infraction in men. Jama,2004,291:1730-1737
[32]Shibata R, Ouchi N, Ito M, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart.Nat Med,2004,10:1384-1389
[33]Liao Y, Takashima S, Maeda N, et al. Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism. Cardiovasc Res,2005,67:705-713
[34]Kato H, Kashiwagi H, Shiraga M, et al. Adiponectin acts as an endogenous antithrombotic factor. Arterioscler Thromb Vasc Biol,2006,26:224-230
[35]Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose-specific protein,adiponectin in obesity. Biochem Biophys Res Commun,1999,257: 79-83
[36]Xu A, Wang Y, Keshaw H, et al. The fat-derived hormone adiponectin alleviates alcholic and nonalcoholic fatty liver diseases in mice. J Clin Invest,2003, 112:91-100
[37]Yamauchi T, Kamon J, Ito Y, et al.loning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature,2003,423:762-769
[38]Musso G, Gsmbino R, Biroli G, et al. Hypoadiponectinemia predicts the severity of hepatic fibrosis and pancreatic Beta-cell dysfunction in nondiabetic nonobese patients with nonalcoholic steatohepatitis. Am J Gastroenterol,2005, 100:2438-2446
[39]Wolf AM, Wolf D, Avila MA, et al. Up-regulation of the anti-inflammatory adipokine adiponectin in acute liver failure in mice. J Hepatol,2006,44:537-543
[40]Masaki T, Chiba S, Tatsukawa H, et al. Adiponectin protects LPS-induced liver injury through modulation of TNF-alpha in KK-Ay obese mice. Hepatology, 2004,40:177-184
[41]Kamada Y, Tsmura S, Kiso S, et al. Enhanced carbon tetracholoride-induced liver fibrosis in mice lacking aiponectin. Gastroenterology,2003,125:1796-1807
[42]Matsumoto H, Tamura S, Kamada Y, et al. Adiponectin deficiency exacerbates lipopolysaccharide/D-galactosamine-induced liver injury in mice. World J Gastroenterol,2003,12:3352-3358
[43]Berner HS, Lyngstadaas SP, Spahr A, et. Al. Adiponectin and its receptors are expressed in bone-forming cells. Bone,2004,35:842-849
[44]Oshima K, Nampei A, Matsuda M, et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun,2005,331:520-526
[45]Shinoda Y, Yamaguchi M, Ogata N, et al. Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways. J Cell Biochem,2006,99:196-208
[1]Hutley L, Prins JB. Fat as endocrine organ:relationship to the metabolic syndrome1.Am J Med Sci,2005,330:2802-2891
[2]Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med,2004,350:2362-2374
[3]Matsuzawa Y. Adipocytokines and metabolic syndrome. Semin Vasc Med, 2005,5:34-39
[4]Rabin KR, Kamari Y, Avni I, et al. Adiponectin:linking the metabolic syndrome to its cardiovascular consequences. Expert Rev Cardiovasc Ther,2005,3: 465-471
[5]Guzik TJ, Korbut R, Adamek-Guzik T. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol,2003,54:469-487.
[6]Tilg H, Moschen AR. Adipocytokines:mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol,2006,6:772-783.
[7]Calabro P,Yeh ET. Obesity, inflammation, and vascular disease:the role of the adipose tissue as an endocrine organ. Subcell Biochem,2007,42:63-91
[8]Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation, 2002,105:1135-1143
[9]Trayhurn P, Wood IS. Signalling role of adipose tissue:adipo2 kines and inflammation in obesity. Biochem Soc Trans,2005,33:1078-1081
[10]Ross R. Atherosclerosis-an inflammatory disease. N Engl J Med,1999, 340:115-126
[11]Verma S and Anderson TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation,2002,105:546-549
[12]Christiansen T, Richelsen B, Bruun JM. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int J Obes Relat Metab Disord,2005,29: 146-150
[13]Pelleymounter MA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science,1995,269:540-543
[14]Lee GH, Proenca R, Montez JM, et al. Abnormal splicing of the leptin receptor in diabetic mice.Nature,1996,379:632-635
[15]Saladin R, De Vos P, Guerre-Millo M, et al. Transient increase in obese gene expression after food intake or insulin administration. Nature,1995,377: 527-529
[16]Geffroy S, De Vos P, Staels B, Duban B, Auwerx J, de Martinville B. Localization of the human OB gene (OBS) to chromosome 7q32 by fluorescence in situ hybridization. Genomics,1995,28:603-604
[17]Zoladz JA, Konturek SJ, Duda K, et al. Effect of moder and ate incremental exercise, performed in fed and fasted state on cardio-respiratory variables leptin and ghrelin concentrations in young healthy men. J Physiol Pharmacol,2005,56:63-85
[18]Kaminski T, Smolinska N, Gajewska A, et al. Leptin and long form of leptin receptor genes expression in the hypothalamus and pituitary during the luteal phase and early pregnancy in pigs. J Physiol Pharmacol,2006,57:95-108
[19]Stallmeyer B, Pfeilschifter J, Frank S. Systemically and topically supplemented leptin fails to reconstitute a normal angiogenic response during skin repair in diabetic ob/ob mice. Diabetologia,2001,44:471-479
[20]Kougias P, Chai H, Lin PH, et al. Effects of adipocyte-derived cytokines on endothelial functions:implication of vascular disease. J Surg Res,2005,126:121-129
[21]Knudson JD, Dincer UD, Zhang C, et al. Leptin receptors are expressed in coronary arteries, and hyperleptnemia causes significant coronary endothelial dysfunction. Am J Physiol Heart Circ Physiol,2005,289:H48-H56
[22]Shek EW, Brands MW, Hall JE. Chronic leptin infusion increases arterial pressure. Hypertension,1998,31:409-414
[23]Galili O, Versari D, Sattler KJ, et al. Early Experimental Obesity Is Associated with Coronary Endothelial Dysfunction and Oxidative Stress. Am J Physiol Heart Circ Physiol,2006, electronic version.
[24]Guzik TJ, Sadowski J, Kapelak B, et al. Systemic regulation of vascular NAD(P)H oxidase activity and nox isoform expression in human arteries and veins. Arterioscler Thromb Vasc Biol,2004,24:1614-1620
[25]Mussa S, Guzik TJ, Black E, et al. Comparative efficacies and durations of action of phenoxybenzamine, verapamil/nitroglycerin solution, and papaverine as topical antispasmodics for radial artery coronary bypass grafting. J Thorac Cardiovasc Surg,2003.126:1798-1805
[26]Black EA, Guzik TJ, West NE, et al. Minimally invasive saphenous vein harvesting:effects on endothelial and smooth muscle function. Ann Thorac Surg.2001,71:1503-1507
[27]Barouch LA, Berkowitz DE, Harrison RW, et al. Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice1.Circulation,2003,108:754-759
[28]Rahmouni K, Morgan DA, Morgan GM, et al. Role of selective leptin resistance in diet induced obesity hypertension. Diabetes,2005,54:2012-2018
[29]Steppan CM, Bailey ST, Bhat S, et al. Hormone resistin links obesity to diabetes. Nature,2001,409:307-312.
[30]Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes1 Nature,2001,409:307-312
[31]Banerjee RR, Rangwala SM, Shapiro JS, et al. Regulation of fasted blood glucose by resistin. Science,2004,303:1195-1198
[32]Jung HS, Park KH, Cho YM, et al. Resistin is secreted from macrophages in atheromas and promotes atherosclerosis. Cardiovas Res,2006,69:76-85
[33]Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to C1q produced exclusively in adipocyte.J Biol Chem,1995,270:26746-26749
[34]Maeda K, Okubo K, Shimomural I, et al. cDNA clong and expression of a novel adipose specific collagen-like factor, apMl (Adipose Most abundant Gene transcript 1). Biochem Biophys Res Commun,1996,221:286-289
[35]Hu E, Liang P, Spieglman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Bio Chem,1996,271:10697-10703
[36]Nakano Y, Tobe T, Choi-Miura NH, et al. Isolation and characterization of GBP28,a novel gelatin-binding protein purified from human plasma. J Biochem, 1996,20:803-812
[37]Pajvani UB, Du X, Combs TP, et al. Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. J Biol Chem,2003,278:9073-9085
[38]Shapiro L, Scherer PE. The crystal structure of a complement-lq family protein suggests an evolutionary link to tumor necrosis factor. Curr Biol,1998,8: 335-338
[39]Tsao TS, Murrey HE, Hug C, et al. Oligomerization state-dependent activation of NF-kappa B signaling pathway by adipocyte complement-related protein of 30 kDa (Acrp30). J Biol Chem,2002,277:359-362
[40]Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature,2003,423:762-769
[41]Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev,2005,26:439-451
[42]Ouchi N, Kihara S, Arita Y. Novel modulator for endothelial adhesion molecules:adipocyte-derived plasma protein adiponectin. Circulation.1999,100: 2473-2476
[43]Ouchi N, Kihara S, Arita Y, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kB signaling through a cAMP dependent pathway. Circulation,2000,102:1296-1301
[44]Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood,2000,96: 1723-1732
[45]Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation,2001,103:1057-1063
[46]Yamauchi T, Kamon J, Waki H, et al. Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem,2003, 278:2461-2468
[47]Okamoto Y, Kihara S, Ouchi N, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation,2002,106(22):2767-2770
[48]Matsuda M, Shimomura I, Sata M, et al. Role of adiponectin in preventing vascular stenosis-the missing link of adipo-vascular axis. J Biol Chem,2002,277: 37487-37491
[49]Arita Y, Kihara S, Quchi N, et al. Adipocyte-derived plasma protein, adiponectin, act as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell. Circulation,2002,105:2893-2898
[50]Paukac L, Huanqpu J, Karnovsky MJ. Platelet-derived growth factor-BB, insulin-like growth factor-1, and phorbol ester activate different signaling pathways for stimulation of vascular smooth muscle cell migration. Exp Cell Res,1998,242: 548-560
[51]Chen H, Montagnani M, Funahashi T, et al. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem,2003,278 21-26
[52]Shibata R, Ouchi N, Ito M, et al.Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med,2004,10:1384-1389
[53]Shibata R, Sato K, Pimentel DR, et al.Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK-and COX-2-dependent mechanisms.Nat Med,2005,11:1096-1103
[54]Fukuhara A, Mat suda M, Nishizawa M, et al. Visfatin:a protein secreted by visceral fat t hat mimics t he effect s of insulin.Science,2005,307:426-430
[55]Samal B, Sun Y, Stearns G, et al. Cloning and characterization of t he cDNA encoding a Novel Human Pre2B2 cell colony enhancing factor. Mol Cell Biol, 1994,14:1431-1437
[56]Ognjanovic S, Bao S, Yamamoto SY, et al. Genomic organization of the gene coding for human pre2B2cell colony enhancing factor and expression in human fetal membranes. J Mol Endo crinol,2001,26:107-117
[57]van der Veer E, Nong Z, O'Neil C, et al. Pre2B2cell colony enhancing factor regulates NAD+dependent protein deacetylase activity and promotes vascular smoot h muscle cell maturation.Circ Res,2005,97:25-34
[58]Kralisch S,Klein J,Lossner U,et al. Hormonal regulation of the novel adipocytokine visfatin in 3T3-LI adipocytes. J endocrinol,2005,185:R1-R8.
[59]Hug C, Lodish HF. Medicine. Visfatin:a new adipokine[J]. Science.2005, 307:366-367
[60]Jia SH, Li Y, Parodo J, et al. Pre2B cell colony enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis [J]. J Clin Invest,2005,113:1318-1327.
[61]van de Veer E, Nong Z, O'Neil C, et al. Pre2B2cell colony enhancing factor regulates NAD+2dependent protein deacety lase activity and promotes vascular smooth muscle cell maturation. Circ Res,2005,97:25-34.
[62]O'Dowd BF,Heiber M,Chan A, et al. A human gene that shows identity with the gene encoding the angiotensin receptor is located on chromosome 11. Gene, 1993,136:355-360
[63]Tatemoto K,Hosoya M,Habata Y, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor.Biochem Biophys Res Commun,1998.251:471-476.
[64]Szokodi I, Tavi P, Foldes G, et al. Apelin, the novel endogenous ligand of the orphan receptor APJ, regulates cardiac contractility. Circ Res,2002,91:434-440
[65]Zhong JC, Huang DY, Liu GF, et al. Effects of all-trans retinoic acid on orphan receptor APJ signaling in spontaneously hypertensive rats. Cardiovasc Res,2005,65:743-750
[66]Lee DK, Cheng R, Nguyen T, et al. Characterization of apelin, the ligand for the APJ receptor. J Neurochem.2000,74:34-41
[67]Tatemoto K, Takayama K, Zou MX, et al. The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism. Regul Pept,2001,99:87-92
[68]Cheng X, Cheng XS, Pang CC. Venous dilator effect of Apelin, an endogenous peptide ligand for orphan APJ receptor, in conscious rats. Eur J Pharm acol,2003,470:171-175
[69]Ashley EA, Powers J,Chen M, et al. The endogenous peptide apelin potently improves cardiac contractility and reduces cardiac loading in vivo Cardiovasc Res,2005,65:73-82.
[70]Chen MM, Ashley EA, Deng DX, et al. Novel role for the potent endogenous inotrope apelin in human cardiac dysfunction. Circulation,2003, 108:1432-1439
[71]Foldes G, Horkay F, Szokodi I, et al. Circulating and cardiac levels of Apelin, the novel ligand of the orphan recep tor APJ, in patients with heart failure. Biochem Biophys Res Commun,2003,308:480-485
[72]Sonnenberg GE, Krakower GR, Kissebah AH1 A novel pathway to the manifestations of metabolic syndrome. Obes Res,2004,12:180-186
[73]Hutley L, Prins JB. Fat as endocrine organ:relationship to the metabolic syndrome. Am J Med Sci,2005,330:280-289
[74]Vincenzo P, James T. Willerson. Direct proinflammatory effect of C-reactive protein on human endothelial cells.Circulation,2000,102:2165-2168
[75]Klein J, Perwitz N, Kraus D, et al. Adipose tissue as source and target for novel therapies. Trends Endocrinol Metab,2006,17:26-32