摘要
[背景]
对于冠心病潜在危险因素的探讨一直以来都是心血管病学领域研究的热点之一,而对脂肪细胞因子的研究则是热点中的焦点。已有研究表明,总脂联素(total adiponectin TAPN)作为一种脂肪细胞因子,对于冠心病的发生、发展具有一定的保护作用,高分子脂联素(hign molecular weight adiponectin HMWAPN)作为TAPN的一种亚型,是其发挥生物学活性的主要成分。目前对于冠心病的预测和预后,脂联素是最有潜力的脂肪因子,但学术界关于脂联素各亚型,尤其是HMWAPN与冠心病相关性及其预后的研究所得出的结论并非一致。富含半胱氨酸的酸性分泌蛋白(Secreted protein and riched in cysteine SPARC)也新渐被人们认识到与冠心病之间有一定的关系,但国内外均未见较大规模的临床研究。
[目的]
探讨血清TAPN、HMWAPN水平及两者之比值(hign molecular weight adiponectin/total adiponectin H/T ratio)和SPARC水平与冠心病患者传统危险因素、冠状动脉病变严重程度以及主要心脑血管不良事件(main adverse cardiovascular cerebral vascular events MACCE)之间的关系。
[方法]
研究对象为以2007年7月至2009年5月之间于北京协和医院因临床疑诊冠心病,住院行冠脉造影检查的北京地区患者,共收集503例,其中对明确诊断冠心病的患者(共449例)进行临床随访,随访截止日期2012年12月。住院期间,收集患者的一般情况、包括冠心病危险因素以及既往相关疾病史等；采集空腹静脉血检测血糖、血脂、超敏C反应蛋白(hsCRP)、肌酐清除率(Creatinine clearance Ccr)、 TAPN、HMWAPN及SPARC等有关指标,评估研究对象的左室射血分数(Left ventricular ejection fraction LVEF),每一个研究对象均行冠状动脉造影检查,并进行Gensini积分、改良Gensini积分、弥漫积分等冠脉病变的定量评估：随访冠心病患者MACCE的发生情况,包括心源性死亡、靶血管再血管化(Target Vessel Revascularization TVR)、随访期间发生的急性冠脉综合征(acute coronary syndromeACS)(包括不稳定心绞痛和急性心肌梗死)、脑卒中或者一过性脑缺血、心功能恶化。总结随访结果,分别分析TAPN、HMWAPN. H/T ratio、SPARC与冠心病各危险因素及冠脉病变严重程度之间的关系；并探讨TAPN、HMWAPN. H/T ratio、 SPARC与冠心病患者预后(发生MACCE)之间的关系。
[结果]
1、平均随访时间为54.44±5.7个月,随访期间发生MACCE的总人数为178例,发生率为39.6%。与第一次随访(2010年3月)结果相比,心源性死亡、靶血管再血管化、脑卒中增长率较高,分别达到了212.5%、116.7%和120.0%。
2、脂联素与冠心病：(1)男性冠心病人群中,血脂异常组的HMWAPN、TAPN水平显著低于正常组(p<0.05或0.01),而在女性冠心病人群中,各亚组之间的HMWAPN、TAPN水平及H/T ratio无显著差异(p>0.05)。(2)相关性分析显示在男性冠心病人群中,HMWAPN、TAPN与冠心病危险因素的数目、肌酐清除率、体重指数呈负相关(P<0.05或0.01),而在女性冠心病人群中,HMWAPN、TAPN水平及H/T ratio与各临床指标无明确相关(p>0.05)。(3) COX回归分析发现：在男性冠心病人群中,低水平的HMWAPN (p=0.022, RR=1.656)及H/Tratio (p=0.002,RR=2.048)是发生MACCE的独立危险因素。在女性冠心病人群中,低水平的HMWAPN(p=0.004, RR=2.832)、TAPN(p=0.003, RR=2.802)是发生MACCE的独立危险因素。(各个指标第一个3分位间距为低水平组)
3. SPARC与冠心病：(1)相关性分析发现：血清SPARC水平与超敏C反应蛋白、Gensini积分、改良的Gensini积分、弥漫积分呈正相关(p<0.05),多重线性回归分析发现,血清SPARC是影响冠脉Gensini积分的独立因素。(2) COX回归分析发现：血清SPARC水平与冠心病人群发生MACCE之间不具有相关性p=.146).(SPARC第3个3分位间距为高水平组)
[结论]
1、随着随访时间的延长,心源性死亡、靶血管再血管化及心功能恶化的比例在冠心病病人总MACCE中比例逐渐提高。
2、男性冠心病人群中MACCE的发生与HMWAPN和]H/T ratio水平降低独立相关,而与TAPN不相关,提示HMWAPN具有保护作用,这种保护作用独立于冠心病传统危险因素的影响。HMWAPN水平的降低可作为男性冠心病患者预后不良的预测指标。
3、女性冠心病人群中MACCE的发生与TAPN. HMWAPN水平降低独立相关,而与H/T ratio不相关,提示TAPN和HMWAPN都起保护作用,这种保护作用也独立于冠心病传统危险因素影响；TAPN和HMWAPN水平降低是影响女性冠心病病人预后的评价指标。
4、SPARC水平与冠状动脉狭窄的严重程度相关,提示可能在冠状动脉粥样硬化的形成及进展过程中起一定的作用,对于冠心病以及病变严重程度具有早期预警的作用。冠心病患者总MACCE的发生与SPARC水平无明显相关性,但对于ACS及心功能恶化的发生,可能具有一定的提示作用。
[Background]
Investigating potential risk factors of coronary artery disease (CAD) has been an emerging hot spot in the filed of cardiology. While focus of which is the study of adipocytokins. As a kind of adipocytokins,numerous researches suggested that total adiponectin play an important protective role in the pathogenesis, development of CAD. High molecular weight adiponectin (HMWAPN), the subtype of adiponectin exerts this biological activity in most of the time. Until now, adiponectin is one of the most potential adipocytokins for the prediction and prognosis of CAD while whether the subtype of which, especially HMWAPN has effect on CAD and its prognosis remains uncertain. In the meanwhile, Secreted protein and riched in cysteine (SPARC) has gradually been recognized that it also has an certain effect on the pathogenesis of CAD while this effect, to our knowledge, was rarely investigated before and not well understood。
[Objective]
To explore the relationship between serum TAPN level、HMWAPN level、 HMW/TOTAL-adiponectin(H/T) ratio、SPARC level and CAD risk factors、the severity of coronary artery in the patients with CAD and to investigate the relationship between the above four factors and prognosis of CAD, mainly include main adverse cardiovascular and cerebral vascular events (MACCE)
[methods]
A total of503hospitalized patients underwent coronary angiography, who were in Beijing, from July2007to May2009in Peking Union Medical College Hostipal were included. All patients' clinical data, including classic cardiovascular risk factors, past medical history, lab tests(include serum HMWAPN TAPN and SPARC), creatinine clearance, left ventricle ejection fraction were collected after admission. Every subject was calculated gensini score、modified gensini score and diffuse score according to their results of coronary angiography to quantify the severity of coronary artery. Those patients (449cases) with proved CAD by coronary angiography were followed up till December2012. The primary end point was the occurrence of major adverse cardiovascular cerebral vascular events (MACCE), including cardiovascular death, targeted vascular revascularization, acute coronary syndrome and deterioration of cardiac function, transient ischemic attack and stroke. And analysis was conducted to identify the relationship between TAPN level、HMWAPN level、HMW/total-adiponectin ratio、 SPARC level and CAD risk factors、the severity of coronary in the patients with CAD and to investigate the relationship between the above four factors and the prognosis of CAD.
[Results]
1,178MACCE occurrenced during the period of follow up (the average follow up month is54.4±5.7), and the incidence of MACCE was39.6%. Compared with the first follow up (March2010) results, cardiac death, target vessel revascularization, stroke had a higher growth rate which reached212.5%,116.7%and120.0%, respectively.
2, Adiponectin and CAD:(1) Serum HMWAPN、TAPN level of dislipidemia were more lower than of normal in male patients with CAD (p<0.05or0.01). While in female patients with CAD, there is no significant difference of Serum HMWAPN、TAPN level and H/T ratio in every subgroups (p>0.05).(2) Correlation analysis revealed that Serum HMWAPN、TAPN level had a negative association with the number of risk factors、body mass index (BMI)、creatinine clearance in male patients with CAD(p<0.05or0.01). While in female patients with CAD, Serum HMWAPN TAPN level and H/T ratio had no association with various clinical indicators (p>0.05).(2) COX regression analysis found that the low level of HMWAPN (p=0.022, RR=1.656) and H/Tratio (p=0.002, RR=2.048) were independent risk factors for occurrence of MACCE in male patients with CAD and low level of HMWAPN (p=0.004, RR=2.832) and TAPN (p=0.003, RR=2.802) were independent risks factors in female patients with CAD.
3, SPARC and CAD:(1) Correlation analysis found that:serum SPARC had a positively correlation with hypersensitive c-reactive protein (hsCRP) and Gensini score, modified Gensini score and diffuse score,(p<0.05), the multifactor linear regression analysis revealed that serum SPARC was an independent factor for the the severity of coronary artery(Gensini score)(p=0.023).(2) COX regression analysis found that serum SPARC levels had no effect on the incidence of MACCE for CAD patients (p>0.05).
[Conclusion]
1, The proportion of cardiac death, target vessel revascularization and deterioration of cardiac function had been gradually rised in the total MACCE with the extension of follow-up.
2, The HMWAPN level and H/T ratio were independent protective factors for the incidence of MACCE in male patients with CAD while TAPN level was irrelevant, And this protective effect was not affected by the traditional risk factors of CAD. The decrease level of HMWAPN could be a predictor of a poor prognosis in this group.
,3, The TAPN and HMWAPN level were independent protective factors for the incidence of MACCE in female patients with CAD while H/T ratio was irrelevant, And this protective effect was also not affected by the traditional risk factors of CAD. The decrease level of HMWAPN and TAPN could be a predictor of a poor prognosis in this group.
4, SPARC level was assocated with the severity of coronary artery and may play a certain role in the pathogenesis of coronary atherosclerosis, and also has a role of early warning for the CAD. SPARC had no significant correlation with the incidence of total MACCE in patients with CAD, but may have some tips for occurrence of ACS and heart function deterioration in future.
引文
[1]中国卫生统计年鉴(2005).中国协和医科大学出版社,2005.
[2]Ford ES, Ajani UA, Croft JB, et al. Explaining the decrease in U.S. deaths from coronary disease,1980-2000. NEngl J Med.2007; 356(23):2388-2398.
[3]Arita Y, Kihara S, Ouchi N. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun.1999; 257:79-83.
[4]Kobashi C, Urakaze M, Kishida M, et al. Adiponectin inhibits endothelial synthesis of interleukin-8. Circ Res.2005; 97 (12) 1245-1252.
[5]Motoshima H, Wu X, Mahadev K, et al. Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. Biochem Biophys Res Commun.2004; 315(2):264-271.
[6]Ohashi K, Ouchi N, Sato K, et al. Adiponectin promotes revascularization of ischemic muscle through a cyclooxygenase 2-dependent mechanism. Mol Cell Biol.2009; 29(13):3487-3499.
[7]Ai M, Otokozawa S, Asztalos BF, et al. Adiponectin:An independent risk factor for coronary heart disease in men in the Framingham offspring Study. Atherosclerosis. 2011;217(2):543-548.
[8]Marso SP, Mehta SK, Frutkin A, et al. Low adiponectin levels are associated with atherogenic dyslipidemia and lipid-rich plaque in nondiabetic coronary arteries. Diabetes Care.2008; 31(5):989-994.
[9]. Ohashi N, Ito C, Fujikawa R, et al. The impact of visceral adipose tissue and high-molecular weight adiponectin on cardio-ankle vascular index in asymptomatic Japanese subjects. Metabolism.2009; 58(7):1023-1029.
[10]Kunita E, Yamamoto H, Kitagawa T, et al. Association between plasma high-molecular-weight adiponectin and coronary plaque characteristics assessed by computed tomography angiography in conditions of visceral adipose accumulation. Circ. 2012; 76(7):1687-1696.
[11]Inoue T, Kotooka N, Morooka T, et al. High molecular weight adiponectin as a predictor of long-term clinical outcome in patients with coronary artery disease. Am J Cardiol.2007; 100(4):569-74.
[12]Kae-Woei Liang, Wen-Jane Lee, Wen-Lieng Lee, et al. Decreased ratio of high-molecular-weight to total adiponectin is associated with angiographic coronary atherosclerosis severity but not restenosis. Clin Chim Acta.2009; 405(1-2):114-118.
[13]von Eynatten M, Hamann A, Twardella D, et al. Atherogenic dyslipidaemia but not total-and high-molecular weight adiponectin are associated with the prognostic outcome in patients with coronary heart disease. Eur Heart J.2008; 29 (10):1307-1315.
[14]Quan Li, Yihua Lu, Lixian Sun,et al. Plasma adiponectin levels in relation to prognosis i n patients with angiographic coronary artery disease. Metabol.2012; 61: 1803-1808.
[15]Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection Evaluation And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel Ⅲ). JAMA.2001; 285(19):2486-2497.
[16]Fava S, Azzopardi J, Muscat HA, et al. Factors that influence outcome in diabetic subjects with myocardial infarction. Diabetes Care.1993; 16:1615-1618.
[17]于丽天,谭慧琼,朱骏等。糖尿病合并非ST段抬高急性冠状动脉综合征患者的临床特点、治疗及远期预后.中华心血管病杂志 2011,39(5)：390-396.
[18]Casula M, Tragni E, Zambon A,et al. C-reactive protein distribution and correlation with traditional cardiovascular risk factors in the Italian population. Eur J Intern Med. 2013;24(2):161-166.
[19]Kaptoge S, Di Angelantonio E, Pennells L,C-reactive protein, fibrinogen, and cardiovascular disease prediction. N Engl J Med.2012; 367(14):1310-1320.
[20]Ryo M, Nakamura T, Kihara S, et al. Adiponectin as a biomarker of the metabolic syndrome. Circ J 2004; 68:975-981.
[21]Fruebis J, Tsao TS, Javorschi S, et al:Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001; 98:2005-2010.
[22]Nishizawa H, Shimomura I, Kishida K, et al. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes 2002; 51: 2734-2741.
[23]Xu A, Chan KW, Hoo RLC, et al. Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes. J Biol Chem 2005; 280:18073-18080.
[24]Tishinsky JM, Dyck DJ, Robinson LE. Lifestyle factors increasing adiponectin synthesis and secretion. Vitam Horm.2012; 90:1-30.
[25]Stepien M, Wlazel RN, Paradowski M,et al, Serum concentrations of adiponectin, leptin, resistin, ghrelin and insulin and their association with obesity indices in obese normo-and hypertensive patients-pilot study. Arch Med Sci.2012; 8(3):431-436.
[26]Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidemia. JClin Endocrinol Metab.2002; 87(6):2764-2769.
[27]Huang KC, Lue BH, Yen RF, et al. Plasma adiponectin levels and metabolic factors in nondiabetic adolescents. Obes Res.2004; 12(1):119-124.
[28]Pyrzak B, Ruminska M, Popko K,et al. Adiponectin as a biomarker of the metabolic syndrome in children and adolescents. Eur J Med Res.2010;15 Suppl 2:147-151
[29]Komura N, Kihara S, Sonoda M, et al. Increment and impairment of adiponectin in renal failure.Cardiovasc Res.2010; 86(3):471-477.
[30]Aso Y, Suganuma R, Wakabayashi S, et al. Anemia is associated with an elevated serum level of high molecular weight (HMW) adiponectin in patients with type 2 diabetes independently of renal dysfunction. Transl Res.2009; 154(4):175-182.
[31]Pischon T, Hu FB, Girman CJ, et al. Plasma total and high molecular weight adiponectin levels and risk of coronary heart disease in women Atherosclerosis.2011; 19(1):322-329.
[32]Sattar N, Watt P, Cherry L, Ebrahim S, et al. High Molecular Weight Adiponectin Is Not Associated with Incident Coronary Heart Disease in Older Women:A Nested Prospective Case-Control Study. J Clin Endocrinol Metab 2008;93(5):1846-1849.
[33]Aso Y, Yamamoto R, Wakabayashi S, et al. Comparison of serum high-molecular weight (HMW) adiponectin with total adiponectin concentrations in type 2 diabetic patients with coronary artery disease using a novel enzyme-linked immunosorbent assay to detect HMW adiponectin. Diabetes.2006;55(7):1954-1960.
[34]El-Menyar A, Rizk N, Al Nabti AD, et al. Total and high molecular weight adiponectin in patients with coronary artery disease. J Cardiovasc Med.2009; 10(4): 310-315.
[35]Lindberg S, Pedersen SH, Mogelvang R et al. Usefulness of Adiponectin as a Predictor of All Cause Mortality in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention Am J Cardiol. 2012;109(4):492-496.
[36]Liang KW, Lee WJ, Lee WL,et al. Decreased ratio of high-molecular-weight to total adiponectin is associated with angiographic coronary atherosclerosis severity but not restenosis. Clin Chim Acta.2009; 405(1-2):114-118.
[37]Kunita E, Yamamoto H, Kitagawa T, et al.Association between plasma high-molecular-weight adiponectin and coronary plaque characteristics assessed by computed tomography angiography in conditions of visceral adipose accumulation. Circ J.2012; 76(7):1687-1696.
[38]Moroi M, Akter S, Nakazato R, et al. Lower ratio of high-molecular-weight adiponectin level to total may be associated with coronary high-risk plaque. BMC Res Notes.2013;6:83.
[39]ShibataR, SatoK, Pimentel DR, et al. Adiponectinprotects against myocardial ischemia reperfusion injury through AMPK-and COX-2 dependent mechanisms. Nat Med.2005;11(10):1096-1103.
[40]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 (11):1296-1301.
[41]Li M, Ho JC, Lai KW, et al. The decrement in circulating endothelial progenitor cells (EPCs) in type 2 diabetes is independent of the severity of the hypoadiponectemia. Diabetes Metab Res Rev.2011; 27(2):185-194.
[42]Arita Y, Kihara S, Ouchi N, et al. Adipocyte-derived plasma protein adiponectin acts 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(24):2893-2898.
[43]Matsuda M, Shimomura I, Sata M, et al, Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Bio Chem.2002; 277(40): 37487-37491.
[44]Okamoto Y, Arita Y, Nishida M, et al. An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res.2000; 32(2):47-50.
[45]Kubota N, Terauchi Y, Yamauchi T, et al. Disruption of adiponectin causes insulin resistance andneointimal formation. JBiol Chem.2002; 277(29):25863-25866.
[46]Natarajan R, Salloum FN, Fisher BJ, et al. Hypoxia inducible factor-1 upregulates adiponectin in diabetic mouse hearts and attenuates post-ischemic injury. J Cardiovasc Pharmacol.2008; 51(2):178-187.
[47]Devaraj S, Torok N, Mohan R, et al. Adiponectin decreases C-reactive protein synthesis and secretion from endothelial cells:evidence for an adipose tissue-vascular loop. Arterioscler Thromb Vase Biol.2008; 28(7):1368-1374.
[1]Koukourakis MI, Giatromanolaki A, Brekken RA, et al. Enhanced expressionof SPARC osteonectin in the tumor-associated stroma of nonsmall celll ungcancer is correlated with markers of hypoxia/acidityand with poor prognosisof patients. Cancer Res.2003; 63(17):5376-5380.
[2Nishie A, Masuda K, Otsubo M, et al. High expression of the Cap43 gene in infiltrating macrophages of human renal cell carcinomas. Clin Cancer Res.2001; 7(7):2145-2151.
[3]Sakai N, Baba M, Nagasima Y, et al. SPARC expression in primary human renal cell carcinoma:upregulation of SPARC in sarcomatoid renal carcinoma. Hum Pathol.2001; 32(10):1064-1070.
[4]Nie J, SageEH. SPARC inhibits adipogenesis by its enhancement of beta-catenin signaling.J. Biol. Chem.2009; 284(2):1279-1290.
[5]Nai M, Van Obberghen E. Van Obberghen E.Inflammation:where is the SPARC in adipose tissue inflammation?. Nat.Rev.Endocrinol.2009; 5(12):648-649.
[6]Kos K, Wilding JP. SPARC:a key player in the pathologies associated with obesity and diabetes. Nat. Rev. Endocrinol.2010; 6(4):225-235
[7]Chavey C, Boucher J, Monthouel-Kartmann MN, et al. Regulation of secreted protein acidic and rich in cysteine during adipose conversion and adipose tissue hyperplasia. Obesity.2006; 14(11):1890-1897.
[8]Nie J, Sage EH. SPARC inhibits adipogenesis by its enhancement of beta-catenin signaling. J Biol Chem.2009; 284(2):1279-1290.
[9]Dobaczewski M, Gonzalez-Quesada C, Frangogiannis NG The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction. J Mol Cell Cardiol 2010; 48(3):504-511.
[10]Schellings MW, Vanhoutte D, Swinnen M, et al. Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction. J Exp Med. 2009; 206(1):113-123.
[11]Brune K, Hong SM, Li A, et al. Genetic and epigenetic alterations of familial pancreatic cancers. Cancer Epidemiol Biomarker Prey.2008; 17(12):3536-3542.
[12]Friesen C, Herr I, Krammer PH, et al. Involvement of the CD95 (APO21/Fas) receptor/ligand system in drug induced apoptosis in leukemia cells. Nat Med.1996; 2(5): 574-577.
[13]Higami Y, Barger JL, PageGP, et al. Energy restriction lowers theexpression of geneslinked to inflammation the eytoskeleton, the extracclutar matrix, andangiogenesisin mouse adipose tissue. JNutr.2006; 136(2):343-352.
[14]Henegar C, Tordjman J, Achard V, et al. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol.2008; 9(1):R14.
[15]Averill MM, Bornfeldt KE. Lipids versus glucose in inflammation and the pathogenesis of macrovascular disease in diabetes. Curr Diab Rep.2009; 9(1):18-25.
[16]Kotani K, Yamada T, Taniguchi N. The association between circulating secreted protein acidic and rich in cysteine (SPARC) and glycosylated haemoglobin (HbA1c) during lifestyle-modified weight reduction intervention in obese male subjects. J Int Med Res.2011; 39(2):528-532.
[17]Chavey C, Beueher J, Monthouel-Kartmann MN, et al. Regulation of secreted protein acidic and rich in cysteine during adipose conversion and adipose tissue hyperpiasia. Obesity.2006; 14(11):1890-1897.
[18]Moore KJ, Tabas I. Macrophages in the pathogenesis of atherosclerosis. Cell.2011; 145(3):341-355.
[19]Raines EW, Lane TF, Iruela-Arispe ML, et al. The extracellular glycoprotein SPARC interacts with platelet derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors. Proc Nat Acad Sci USA.1992; 89(4):1281-1285.
[20]Gossl M, Modder UI, Atkinson EJ, et al. Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis Osteocalin Expression. JAm Coll Cardiol.2008; 52(16):1314-1325.
[21]Kos K, Wong S, Tan B, et al. Regulation of the jibrosis and angiogcncsis promoter SPARC In human adipose tissue by weight change, leptin, insulin and glucose. Diabetes. 2009; 58(8):1780-1788
[22]Gadeau AP, Chaulet H, Daret D, et al. Time course of osteopontin, osteocalcin, and osteonectin accumulation and calcification after acute vessel wall injury. J Histochem Cytochem.2001; 49(1):79-86.
[23]Kang YJ, Stevenson AK, Yau PM, et al. Sparc protein is required for normal growth of zebrafish otoliths. JAssoc Res Otolaryngol.2008; 9(4):436-451.
[24]Takahashi M, Nagaretani H, Funahashi T, et al. The expression of SPARC in adipose tissue and its increased plasma concentration in patients with coronary artery disease. Obes Res.2001; 9(7):388-393.
[25]Ragino YI, Kashtanova EV, Chernjavski AM, et al. Blood Level of Osteonectin in Stenosing Atherosclerosis and Calcinosis of Coronary Arteries. Bull Exp Bio Med.2011; 151(3):370-373.
[26]Gabbasov ZA, Agapov AA, Saburova OS, et al. Circulating stromal osteonectin-positive progenitor cells and stenotic coronary atherosclerosis. Can J Pharmacol.2007; 85(3-4):295-300.
[27]Schellings MW, Vanhoutte D, Swinnen M, et al. Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction. J Exp Med.. 2009; 206(1):113-123.
[28]Xue RX, Laser M, Han H, et al. Fibroblast migration after myocardial infarction is regulated by transient SPARC expression. J Mol Med.2006; 84(3):241-252
[29]Ridinger H, Rutenberg C, Lutz D, et al. Expression and tissue localization of beta-catenin, alpha-actinin and chondroitin sulfate proteoglycan 6 is modulated during rat and human left ventricular hypertrophy. Exp Mol Pathol.2009; 86(1):23-31.
[1]胡盛寿、孔灵芝,中国心血管病报告.2011.
[2]中国卫生统计年鉴(2005).中国协和医科大学出版社,2005.
[3]Balagopal PB, de Ferranti SD, Cook S, et al. Nontraditional Risk Factors and Biomarkers for Cardiovascular Disease:Mechanistic, Research and Clinical Considerations for Youth, Circulation.2011; 123(23):2749-2769.
[4]Arita Y, Kihara S, Ouchi N, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun.1999; 257(1):79-83.
[5]Hara K, Yamauchi T, Kadowaki T, et al. Adiponectin:an adipokine linking adipocytes and type 2 diabetes in humans. Curr Diab Rep.2005; 5(2):136-140.
[6]Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev.2005; 26(3):439-451.
[7]Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to Clq, produced exclusively in adipocytes. JBiol Chem.1995; 270(45):26746-26749.
[8]Viengchareun S, Zennaro MC, Pascua-1 Le Tallec L, et al. Brown adipocytes are novel sites of expression and regulation of adiponetin and resistin. FEBS Lett.2002; 532(3):345-350.
[9]Fruebis J, Tsao TS, Javorschi S, et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001; 98(4):2005-2010.
[10]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(11):1288-1295.
[11]Maeda K, Okubo K, Shimomura I, et al. cDNA cloning and expression of an novel adipose-specific collagen-like factor, apMl(Adipose most abundant G ene transcriptl). Biochem Biophys Res Commun.1996; 221(2):286-289.
[12]Vasseur F, Helbecque N, Dina C, et al. Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type2 diabetes in French Caucasians. Human Mol Genetics.2002; 11(21):2607-2614.
[13]Ohashi K, Ouchi N, Kihara S, et al. Adiponectin 1164T mutation is associated with the metabolic syndrome and coronary artery disease. J Am Coll Cardiol.2004; 43(7): 1195-1200.
[14]Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature.2003; 423(6941):762-769.
[15]Hug C, Wang J, Ahmad NS, et al. T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin. Proc Natl Acad Sci USA.2004; 101(28):10308-10313.
[16]Ding G, Qin Q, He N, et al. Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor gamma. J Mol Cell Cardiol.2007; 43(1):73-84.
[17]Denzel MS, Scimia MC, Zumstein PM, et al. T-cadherin is critical for adiponectin-mediated cardioprotection in mice. J Clin Invest.2010; 120(12):4342-4352.
[18]Chen Z, Peng IC, Sun W, et,al. AMP-activated protein kinase functionally phosphorylates endothelial nitric oxide synthase Ser633. Circ Res.2009; 104(4): 496-505.
[19]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(1):99-109.
[20]Chen H, Montagnani M, Funahashi T, et al. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem.2003; 278:45021-45026.
[21]Matsuzawa Y, Funahashi T, Kihara S:Adiponectin and metabolic syndrome. Arterioscler Thromb Vase Biol.2004; 24(1):29-33.
[22]Valsamaki G, Chetty R, McTernan PG, et al. Fasting serum adiponectin concentration is reduced in Indo-Asian subjects and is related to HDL-C. Diabetes Obes Metab.2003; 5(2):131-135.
[23]Cnop M, Havel PJ, Utzschneider KM, et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins:evidence for independent roles of age and sex. Diabetologia.2003; 46(4):459-469.
[24]Medina-Bravo P, Meza-Santibanez R., Rosas-Fernandez P, et al. Decrease in serum adiponectin levels associated with visceral fat accumulation independent of pubertal stage in children and adolescents. Arch Med Res.2011; 42(2):115-121.
[25]Franz MJ, Van Wormer JJ, Crain AL, et al. Weight-loss out-comes:a systematic review and meta-analysis of weight-loss clinical trials with a minimum 1-year follow-up. JAm Diet Assoc.2007; 107(10):1755-1767.
[26]Tishinsky JM, Dyck DJ, Robinson LE, Lifestyle Factors Increasing Adiponectin Synthesis and Secretion. Vitam Horm.2012; 90:1-30.
[27]Milan G, Granzotto M, Scard A, et al. Resistin and adiponectin expression in visceral fat of obese rats:effect of weight loss. Obes Res.2002; 10(11):1095-1103.
[28]Motoshima H, Wu X, Sinha MK, et al. Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes:effects of insulin and rosiglitazone. J Clin Endocrinol Metab.2002; 87(12):5662-5667.
[29]Maeda N, Takahashi M, Funahashi T, et al. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes.2001; 50(9):2094-2099.
[30]Lihn AS, Pedersen SB, Richelsen B. Adiponectin:action, regulation and association to insulin sensitivity. Obes Rev.2005; 6(1):13-21.
[31]Lwaki M, Wleeck A, Maeda N, et al. Induction of adiponectin, A fat derived antidiabetic and antiatherogenic factor by nuclear receptors. Diabetes.2003; 52(7): 1655-1663.
[32]Degawa-Yamauchi M, Moss KA, Bovenkerk JE,et al. Regulation of adiponectin expression in human adipocytes:effects of adiposity, glucocorticoids, and tumor necrosis factor alpha. Obes Res.2005; 13(4):662-669.
[33]Wu X, Mahadev K, Fuchsel L, et al. Adiponectin suppresses IkappaB kinase activation induced by tumor necrosis factor-alpha or high glucose in endothelial cells: role of camp and amp kinase signaling. Am J Physiol Endocrinol Metab.2007; 293(6): 1836-1844.
[34]Steppan CM, Wang J, Whiteman EL,et al. Activation of SOCS-3 by resistin. Mol CellBiol.2005;25(4):1569-1575.
[35]Reinehr T, Roth C, Menke T, et al. Adiponectin before and after weight loss in obese children. J Clin Endocrinol Metab.2004; 89(8):3790-3794.
[36]Zhu W, Cheng KK, Vanhoutte PM, et al. Vascular effects of adiponectin:molecular mechanisms and potential therapeutic intervention. Clin Sci.2008; 114(5):361-374.
[37]Goldstein BJ, Scalia R. Adiponectin:a novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab.2004; 89(6):2563-2568.
[38]LinLY, Lin CY, Su TC, et al. Angiotensin II-induced apoptosis in human endothelial cells is inhibited by adiponectin through restoration of the association between endothelial nitricoxide synthase and heat shock protein90. FEBS Lett.2004; 574(1-3): 106-110.
[39]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(11):1296-1301.
[40]Kobashi C, Urakaze M, Kishida M, et al. Adiponectin inhibits endothelial synthesis of interleukin-8. Circ Res.2005; 97 (12) 1245-1252.
[41]Motoshima H, Wu X, Mahadev K, et al. Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. Biochem Biophys Res Commun.2004; 315(2):264-271.
[42]Ouchi N, Ohishi M, Kihara S, et al. Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension.2003; 42(2):231-234.
[43]Okamoto Y, Kihara S, Ouchi N, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation.2002; 106(22):2767-2770.
[44]Li M, Ho JC, Lai KW, et al. The decrement in circulating endothelial progenitor cells (EPCs) in type 2 diabetes is independent of the severity of the hypoadiponectemia. Diabetes Metab Res Rev.2011; 27(2):185-194.
[45]Arita Y, Kihara S, Ouchi N, et al. Adipocyte-derived plasma protein adiponectin acts 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(24):2893-2898.
[46]Matsuda M, Shimomura I, Sata M, et al, Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Bio Chem.2002; 277(40): 37487-37491.
[47]Okamoto Y, Arita Y, Nishida M, et al. An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res.2000; 32(2):47-50.
[48]Kubota N, Terauchi Y, Yamauchi T, et al. Disruption of adiponectin causes insulin resistance andneointimal formation. J Biol Chem.2002; 277(29):25863-25866.
[49]Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasmaprotein, adiponectin, suppresses lipid accumulation and class Ascavenger receptor expression in human monocyte-derived macrophages. Circulation.2001; 103(8):1057-1063.
[50]Okamoto Y, Folco EJ, Minami M, et al. Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Cir Res.2008; 102(2):218-225.
[51]Kumada M, Kihara S, Ouchi N, et al, Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation.2004; 109(17):2046-2049.
[52]Takemura Y, Ouchi N, Shibata R, et al. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest.2007; 117(2):375-386.
[53]Zhou Y, Wei Y, Wang L,et al. Decreased adiponectin and increased inflammation expression in epicardial adipose tissue in coronary artery disease. Cardiovasc Diabetol. 2011; 10(1):2.
[54]Karastergiou K, Evans I, Ogston N,et al. Epicardial adipokines in obesity and coronary artery disease induce atherogenic changes in monocytes and endothelial cells. Arterioscler Thromb Vase Biol.2010; 30(7):1340-1346.
[55]Natarajan R, Salloum FN, Fisher BJ, et al. Hypoxia inducible factor-1 upregulates adiponectin in diabetic mouse hearts and attenuates post-ischemic injury. J Cardiovasc Pharmacol.2008; 51(2):178-187.
[56]Devaraj S, Torok N, Mohan R, et al. Adiponectin decreases C-reactive protein synthesis and secretion from endothelial cells:evidence for an adipose tissue-vascular loop. Arterioscler Thromb Vase Biol.2008; 28(7):1368-1374.
[57]Ohashi K, Parker JL, Ouchi N, et al. Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem.2010; 285(9):6153-6160.
[58]Kumada M, Kihara S, Ouchi N,et al.Adiponectin specifically increased tissue inhibit or of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation.2004; 109(17):2046-2049.
[59]Ohashi K, Ouchi N, Sato K, et al. Adiponectin promotes revascularization of ischemic muscle through a cyclooxygenase 2-dependent mechanism. Mol Cell Biol.2009; 29(13):3487-3499.
[60]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(5):671-674.
[61]Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vase Biol.2003; 23(1):85-89.
[62]Ai M, Otokozawa S, Asztalos BF, et al. Adiponectin:An independent risk factor for coronary heart disease in men in the Framingham offspring Study. Atherosclerosis. 2011;217(2):543-548.
[63]刘岩,邹大进,李慧等.低脂联素血症是冠状动脉粥样硬化严重程度的重要标志.中华内分泌代谢杂志.2005；21(1)：5-8.
[64]Otsuka F, Sugiyama S, Kojima S, et al. Plasma adiponectin levels are associated with coronary lesion complexity in men with coronary artery disease. J Am Coll Cardiol. 2006; 48(6):1155-1162.
[65]Marso SP, Mehta SK, Frutkin A, et al. Low adiponectin levels are associated with atherogenic dyslipidemia and lipid-rich plaque in nondiabetic coronary arteries. Diabetes Care.2008; 31(5):989-994.
[66]Nakamura Y, Shimada K, Fukuda D, et al. Implications of plasma concentrations of adiponectin in patients with coronary artery disease. Heart.2004; 90(5):528-533.
[67]Cavusoglu E, Ruwende C, ChopraV, et al. Adiponectin is an independent predictor of all cause mortality, cardiac mortality, and myocardial infarct ion inpatients presenting with chest pain. EurHeart J.2006; 27(19):2300-2309.
[68]ShibataR, SatoK, Pimentel DR, et al. Adiponectinprotects against myocardial ischemia reperfusion injury through AMPK-and COX-2 dependent mechanisms. Nat Med 2005; 11(10):1096-1103.
[69]IshikawaY, AkasakaY, Ishii T, et al. Changes in the distribution pattern of gelatin-binding proteinof 28kDa(adiponectin) in myocardial remodeling after ischaemic injury. Histopathology.2003; 42(1):43-52.
[70]Pischon T, Girman CJ, Hotamisligil GS, et al. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA.2004; 291(14):1730-1737.
[71]Lawlor DA, Davey Smith G, Ebrahim S, et al. Plasma adiponectin levels are associated with insulin resistance, but do not predict future risk of coronary heart disease in women. J Clin Endocrinol Metab.2005; 90(10):5677-5683.
[72]Lindberg S, Pedersen SH, Mogelvang R,et al. Usefulness of Adiponectin as a Predictor of All Cause Mortality in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention. Am J Cardiol. 2012; 109(4):492-496.
[73]Miyazaki T, Shimada K, Mokuno H, et al. Adipocyte derived plasma protein, adiponectin, is associated with smoking status in patients with coronary artery disease. Heart.2003; 89(6):663.
[74]Brambilla P, Antolini L, Street ME,et al. Adiponectin and hypertension in normal-weight and obese children. Am JHypertens.2013; 26(2):257-264.
[75]Nanayakkara G, Kariharan T, Wang L, The cardio-protective signaling and mechanisms of adiponectin. Am J Cardiovasc Dis.2012; 2(4):253-266.
[76]Ohashi K, Kihara S, Ouchi N, et al. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension.2006; 47(6):1108-1116.
[77]Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidemia. JClin Endocrinol Metab.2002; 87(6):2764-2769.
[78]Huang KC, Lue BH, Yen RF, et al. Plasma adiponectin levels and metabolic factors in nondiabetic adolescents. Obes Res.2004;12(1):119-124.
[79]Pyrzak B, Ruminska M, Popko K,et al. Adiponectin as a biomarker of the metabolic syndrome in children and adolescents. Eur JMed Res.2010; 15 Suppl 2:147-151
[80]Tian L, Luo N, Klein RL, et al. Adiponectin reduces lipid accumulation in macrophage foam cells. Atherosclerosis.2009; 202(1):152-161.
[81]Abdelgadir M, Karlsson AF, et al. Low serum adiponectin concentrations are associated with insulin sensitivity independent of obesity in Sudanese subjects with type 2 diabetes mellitus. Diabetol Metab Syndr.2013; 5(1):15.
[82]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(10):1274-1278.
[83]Manigrasso MR, Ferroni P, Santilli F, et al:Association between circulating adiponectin and interleukin-10 levels in android obesity:effects of weight loss. J Clin Endocrinol Metab.2005; 90:5876-5879.
[84]Kishimoto N, Okita K, Takada S, et al. Lipoprotein metabolism, insulin resistance, and adipocytokine levels in Japanese female adolescents with a normal body mass index and high body fat mass. Circ J.2009; 73(3):534-539.
[85]Tishinsky JM, Dyck DJ, Robinson LE. Lifestyle factors increasing adiponectin synthesis and secretion. Vitam Horm.2012; 90:1-30.
[86]Stepien M, Wlazel RN, Paradowski M,et al, Serum concentrations of adiponectin, leptin, resistin, ghrelin and insulin and their association with obesity indices in obese normo-and hypertensive patients-pilot study. Arch Med Sci.2012; 8(3):431-436.
[87]Calvani M, Scarfone A, Granato L, et al. Restoration of adiponectin pulsatility in severely obese subjects after weight loss. Diabetes.2004; 53(4):939-947.
[88]Weyer C, Funahashi 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(5):1930-1935.
[89]Bandyopadhyay GK, Yu JG, Ofrecio J, et al. Increased malonyl-CoA levels in muscle from obese and type 2 diabetic subjects lead to decreased fatty acid oxidation and increased lipogenesis; thiazolidinedione treatment reverses these defects. Diabetes.2006; 55(8):2277-2285.
[90]Nicholson W, Wang NY, Baptiste-Roberts K,et al. Association between adiponectin and tumor necrosis factor-alpha levels at eight to fourteen weeks gestation and maternal glucose tolerance:the parity, inflammation, and diabetes study. J Womens Health (Larchmt).2013; 22(3):259-266.
[91]Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vase Biol.2000; 20(6): 1595-1599.
[92]Hara K, Horikoshi M, Yamauchi T, et al.Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care.2006; 29(6):1357-1362.
[93], Ohashi N, Ito C, Fujikawa R, et al. The impact of visceral adipose tissue and high-molecular weight adiponectin on cardio-ankle vascular index in asymptomatic Japanese subjects. Metabolism.2009; 58(7):1023-1029.
[94]Kunita E, Yamamoto H, Kitagawa T, et al. Association between plasma high-molecular-weight adiponectin and coronary plaque characteristics assessed by computed tomography angiography in conditions of visceral adipose accumulation. Circ. 2012; 76(7):1687-1696.
[95]Pajvani UB, Hawkins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin,correlates with thiazolidinedione-mediated improvement in insulin sensitivity. Biol Chem 2004; 279(13):12152-12162.
[96]Kawamoto R, Tabara Y, Kohara K, et al. Serum high molecular weight adiponectin correlates with arterial stiffness in community-dwelling persons. Endocr Res.2011; 36(2): 53-63.
[97]Indulekha K, Surendar J, Anjana R, et al. Circulating levels of high molecular weight(HMW) adiponectin and total adiponectin in relation to fat distribution, oxidative stress and in flammation in Asian Indians. Dis Markers.2012; 33(4):185-192.
[98]Seino Y, Hirose H, Saito I, et al. High molecular weight multimer form of adiponectin as a useful marker to evaluate insulin resistance and metabolic syndrome in Japanese men. Metabolism.2007; 56(11):1493-1499.
[99]Hara K, Uchida T, Takebayashi K, et al. Determinants of Serum High Molecular Weight (HMW)Adiponectin Levels in Patients with Coronary Artery Disease: Associations with Cardio-renal-anemia Syndrome. Intern Med.2011; 50(24):2953-2960.
[100]Eglit T, Lember M, Ringmets I, et al. Gender differences in ser um high-molecular-weight adiponectin levels in metabolic syndrome. Eur J Endocrinology. 2013; 168(3):385-391.
[101]Kobayashi H, Ouchi N, Kihara S, et al. Selective suppression of endothelial cell apoptosis by the high molecular weight form of adiponectin. Circ Res.2004; 94(5): 27-31.
[102]Aso Y, Yamamoto R, Wakabayashi S, et al. Comparison of serum high-molecular-weight (HMW) adipone ctin with total adiponectinc on centrations in type 2 diabetic patients with coronary artery disease using a novel enzyme-linked immunosorbent assay to detect HMW adiponectin. Diabetes.2006; 55(7):1954-60.
[103]Tonelli J, Li W, Kishore P, et al. Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes. Diabetes.2004; 53(6):1621-1629.
[104]Inoue T, Kotooka N, Morooka T, et al. High molecular weight adiponectin as a predictor of long-term clinical outcome in patients with coronary artery disease. Am J Cardiol.2007; 100(4):569-74.
[105]von Eynatten M, Humpert PM, Bluemm A, et al. High-molecular weight adiponectin is independently associated with the extent of coronary artery disease in men. Atherosclerosis.2008; 199 (1):123-128.
[106]Inoue T, Kotooka N, Morooka T, et al. High Molecular Weight Adiponectin as a Predictor of Long-Term Clinical Outcome in Patients With Coronary Artery Disease. Am J Cardiol.2007; 100(4):569-574.
[107]Kae-Woei Liang, Wen-Jane Lee, Wen-Lieng Lee, et al. Decreased ratio of high-molecular-weight to total adiponectin is associated with angiographic coronary atherosclerosis severity but not restenosis. Clin Chim Acta.2009; 405(1-2):114-118.
[108]Noriyuki K, Shinji K, Mina S, et al. Clinical Significance of High-Molecular Weight Form of Adiponectin in Male Patients With Coronary Artery Disease. Circ J. 2008; 72(1):23-28.
[109]Eiji K, Hideya Y, Toshiro K, et al. Association Between Plasma High-Molecular-Weight Adiponectin and Coronary Plaque Characteristics Assessed by Computed Tomography Angiography in Conditions of Visceral Adipose Accumulation. Circ J.2012; 76(7):1687-1696.
[110]Moroi M, Akter S, Nakazato R, et al. Lower ratio of high-molecular-weight adiponectin level to total may be associated with coronary high-risk plaque. BMC Research Notes.2013; 6:83.
[111]Yano Y, Toshinai K, Inokuchi T, et al. Plasma des-acyl ghrelin, but not plasma HMW adiponectin, is a useful cardiometabolic marker for predicting atherosclerosis in elderly hypertensive patients. Atherosclerosis.2009; 204(2):590-594.
[112]Pischon T, Hu FB, Girman CJ, et al. Plasma total and high molecular weight adiponectin levels and risk of coronary heart disease in women. Atherosclerosis.2011; 219(1):322-329.
[113]von Eynatten M, Hamann A, Twardella D, et al. Atherogenic dyslipidaemia but not total-and high-molecular weight adiponectin are associated with the prognostic outcome in patients with coronary heart disease. Eur Heart J.2008; 29 (10):1307-1315.
[114]Tsutamoto T, Tanaka T, Sakai H, et al. Total and high molecular weight adiponectin, haemodynamics, and mortality in patients with chronic heart failure. Eur Heart J.2007; 28(14):1723-1730.
[115]Brune K, Hong SM, Li A, et al. Genetic and epigenetic alterations of familial pancreatic cancers. Cancer Epidemiol Biomarker. Prev.2008; 17(12):3536-3542.
[116]Friesen C, Herr I, Krammer PH, et al. Involvement of the CD95 (APO21/Fas) receptor/ligand system in drug induced apoptosis in leukemia cells. Nat Med.1996; 2(5):574.
[117]Porter PL, Sage EH, Lane TF.et al. Distribution of SPARC in normal and neoplastic human tissue. JHistochem Cytochem.1995; 43(8):791-800.
[118]Kupption C, Motamed K, Sage EH,et al. SPARC (BM-40,osteonectin) inhibits the mitogenic effect of vascular endothelial growth factor on micro vascular endothelial cells. JBiol Chem.1998; 273(45):29635-29640.
[119]Framson PE, Sage EH. SPARC and tumor growth:where the seed meets the soil. J Cell Biochem.2004; 92(4):679-690.
[120]崔永,王天佑.SPARC与恶性肿瘤.中华医学杂志.2005；85(9)：642-644.
[121]Kos K, Wilding JP. SPARC:a key player in the pathologies associated with obesity and diabetes. Nat. Rev. Endocrinol 2010; 6(4):225-235
[122]Nie J, Sage EH. SPARC inhibits adipogenesis by its enhancement of beta-catenin signaling. JBiol Chem.2009; 284(2):1279-1290.
[123]O'Connor, K. C., Song, H., Rosenzweig, et al. Extracellular matrix substrata alter adipocyte yield and lipogenesis in primary cultures of stromal-vascular cells from human adipose. Biotechnol Lett.2003; 25(23):1967-1972.
[124]Bradshaw, A. D., Graves, D. C., Motamed K, et al. SPARC-null mice exhibit increased adiposity without significant differences in overall body weight. Proc Natl Acad Sci. USA.2003; 100(10):6045-6050.
[125]Henegar C, Tordjman J, Achard V, et al. Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity. Genome Biol.2008; 9(1):R14.
[126]Averill MM, Bornfeldt KE. Lipids versus glucose in inflammation and the pathogenesis of macro vascular disease in diabetes. Curr Diab Rep.2009; 9(1):18-25.
[127]Higami Y, Barger JL, Page GP, etal. Energy restriction lowers the expression of genes linked to inflammation the cytoskeleton, the extracellular matrix, and angiogenesis in mouse adipose tissue. JNutr.2006; 136(2):343-352.
[128]Kos K, Wong S, Tan B, et al. Regulation of the fibrosis and angiogenesis promoter SPARC/osteonectin in human adipose tissue by weight change, leptin, insulin, and glucose. Diabetes.2009; 58(8):1780-1788.
[129]Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev. 2005; 26(3):439-451.
[130]索朗曲珍,杨刚毅,李志勇等.糖调节受损和2型糖尿病患者血浆骨连接素水平改变.中国糖尿病杂志.2012；20(5)：325-328.
[131]Kotani K, Yamada T, Taniguchi N. The association between circulating secreted protein acidic and rich in cysteine (SPARC) and glycosylated haemoglobin (HbA(lc)) during lifestyle-modified weight reduction intervention in obese male subjects. J Int Med Res.2011; 39(2):528-532.
[132]Reding T,Wagner U,Silva AB, et al. Inflammation-dependent expression of SPARC during development of chronic pancreatitis in WBN/Kob rats and a microarray gene expression analysis. Physio Genomics.2009; 38(2):196-204.
[133]Taneda S, Pippin JW, Sage EH, et al. Amelioration of diabetic nephropathy in SPARC-null mice. J Am Soc Nephrol.2003; 14(4):968-980.
[134]Yunker CK, Golembieski W, Lemke N, et al. SPARC-induced increase in glioma matrix and decrease in vascularity are associated with reduced VEGF expression and secretion. Int J Cancer.2008; 122(12):2735-2743.
[135]Socha MJ, Manhiani M, Said N, et al. Secreted protein acidic and rich in cysteine deficiency ameliorates renal inflammation and fibrosis in angiotensin hypertension. Am J Pathol.2007; 171(4):1104-1112.
[136]Bradshaw AD, Sage EH. SPARC, a matricellular protein that functions in cellular differentiation and tissue response to injury. JClin Invest.2001; 107(9):1049-1054.
[137]Takahashi M, Nagaretani H, Funahashi T, et al. The Expression of SPARC in Adipose Tissue and its Increased Plasma Concentration in Patients with Coronary Artery Disease. Obes Res.2001; 9(7):388-393.
[138]Ragino YI, Kashtanova EV, Chernjavski AM, et al. Blood Level of Osteonectin in Stenosing Atherosclerosis and Calcinosis of Coronary Arteries. Bull Exp Biol Med.2011; 151(3):370-373.
[139]Gabbasov ZA, Agapov AA, Saburova OS, et al. Circulating stromal osteonectin-positive progenitor cells and stenotic coronary atherosclerosis. Can J Physiol Pharmacol.2007; 85(3-4):295-300.
[140]Raines EW, Lane TF, Iruela-Arispe ML, et al. The extracellular glycoprotein SPARC interacts with platelet derived growth factor (PDGF)-AB and-BB and inhibits the binding of PDGF to its receptors. Proc Nat Acad SciUSA.1992; 89(4):1281-1285.
[141]Gossl M, Modder UI, Atkinson EJ, et al. Osteocalcin expression by circulating endothelial progenitor cells in patients with coronary atherosclerosis Osteocalin Expression. J Am Coll Cardiol.2008; 52(16):1314-1325.
[142]Kang YJ, Stevenson AK, Yau PM, et al. Sparc protein is required for normal growth of zebrafish otoliths. JAssoc Res Otolaryngol.2008; 9(4):436-451.
[143]Dobaczewski M, Bujak M, Zymek P, et al. Extracellular matrix remodeling in canine and mouse myocardial infarcts. Cell Tissue Res.2006; 324(3):475-488.
[144]Wu RX, Laser M, Han H,et al. Fibroblast migration after myocardial infarction is regulated by transient SPARC expression. JMol Med.2006; 84(3):241-252.
[145]Gabbasov ZA, Agapov AA, Saburova OS, et al. Detection of circulating stromal stem cells with osteogenic potential in the blood of coronary patients by laser flow cytometry. Bull Exp Biol Med.2005; 139(2):237-240.
[146]Schellings MW, Vanhoutte D, Swinnen M, et al. Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction. The Journal of Experimental Medicine.2009; 206(1):113-23.