北京地区汉族冠心病患者的脂联素水平与冠心病临床特点及预后关系的分析
摘要
背景：
据报道冠心病(coronary artery disease, CAD)患者冠心病危险因素具有民族及地区的差异性,而这些危险因素与冠状动脉病变的严重程度具有一定的相关性。近年来新发现的冠心病危险因素中,较多研究均支持低脂联素血症与冠心病及冠心病危险因素具有一定的相关性,并且脂联素具有种族特异性。
目的：
研究北京地区汉族冠心病患者的冠心病危险因素的特点及临床表现,探讨脂联素(adiponectin, APN)水平与冠心病危险因素的关系,APN和冠心病患者的主要心脑血管不良事件的关系。
材料和方法：
以2007年7月至2009年5月在北京协和医院因胸痛住院行冠脉造影检查的北京地区汉族患者为研究对象,共收集503例,对其中明确诊断冠心病的患者进行临床随访,随访截止日期2010年3月17(最长随访31月,最短1月,平均随访19月)。就诊住院当日,所有患者均收集其一般信息、冠心病危险因素以及既往患病信息等,并采集静脉血检测空腹静脉血浆葡萄糖、血脂、APN等指标,并行冠状动脉造影检查。同时评估调查对象的肌酐清除率(Creatinine clearance Ccr)、左室射血分数等临床特点,符合冠心病诊断标准的研究对象纳入随访观察,记录终点事件发生情况。终点事件主要指心脑血管主要不良事件(major adverse cardiac and cerebral vascular events, MACCE),它的具体内容包括心源性死亡、非心源性死亡、靶血管病变重建、随访期间发生的心肌梗死、脑卒中或者一过性脑缺血、需要住院治疗的不稳定心绞痛和心功能衰竭,其中不稳定心绞痛和心肌梗死并为急性冠脉综合症。分析冠心病危险因素与冠脉狭窄程度及冠脉积分的关系；探讨冠心病患者预后的影响因素及脂联素水平对冠心病患者预后的价值。
结果：
1、北京地区汉族冠心病患者人群中,男性[P＜0.01, OR=2.648,95%CI(1.494-4.692)]、2型糖尿病[P＜0.01, OR=2.399,95%CI (1.251-4.602)]、吸烟[P＜0.01, OR=4.441,95%CI (1.356-14.548)]为其冠心病主要危险因素。
2、通过冠脉积分对冠心病患者冠脉病变的严重程度与传统的心血管疾病危险因素分析得出,男性、2型糖尿病及高血压病与冠脉病变严重程度相关(P<0.01)。
3、与对照组比较,冠心病患者可以伴随左室射血功能减退[P<0.01,95%CI(0.874-5.829)],肾脏功能下降[P<0.01,95%CI(5.137-17.594)],超敏C反应蛋白(HsCRP)水平升高[P<0.01,95%CI(1.298-3.013)],而且这些参数变化与冠脉病变严重程度相关。
4、冠心病患者的MACCE发生与冠脉狭窄程度[P<0.05,95%CI(3.973-19.401)]、超声左室射血分数[P<0.01,95%CI(0.859-2.523)]及HsCRP水平[P<0.01,95%CI(1.342-6.219)]具有一定的相关性。
5、APN水平与冠心病多种危险因素具有相关性,多元回归分析显示低APN血症的冠心病患者出现MACCE的风险增高, (RR=0.43,P<0.05),且不受冠心病传统危险因素、临床特点及冠脉病变严重程度的影响。
结论：
1、在传统的冠心病危险因素中,吸烟、男性及2型糖尿病与北京地区汉族冠心病患者联系更加紧密,而且心肾功能下降和HsCRP水平升高与冠脉病变严重程度具有一定相关性。
2、低APN血症和与多个冠心病危险因素具有相关性,是冠心病患者预后的较好的预测因子。
Background
The importance of different cardiovascular risk factors varies among different countries and ethnicities, which are also associated with degree of coronary artery severity. Hypoadiponectinemia has been reported to be associated with cardiovascular disease and cardiovascular risk factors, and plasma adiponectin level is different among different ethnicities
Objective
To analyse distribution characteristics of cardiovascular risk factors and clinical characteristics within patients with coronary artery disease in Beijing Han. To explore the relationship between adiponectin level and cardiovascular risk factors, and to investigate the relationship between adiponectin and prognosis of cardiovascular diseases, especially coronary artery disease.
Design and method
A total of 503 hospitalized patients undergoing coronary angiography, who were Beijing Han, from July 2007 to May 2009 in Peking Union Medical College Hostipal were included. All patients' clinical data, including classic cardiovascular risk factors, creatinine clearance, left ventricle ejection fraction were recorded after admission and those with cardiovascular disease were followed up till March 17, 2010(1month to 31monthes). The primary end point was the combined occurrence of major adverse cardiovascular cerebral vascular events(MACCE), including cardiovascular death, non-cardiovascular death, targeted vascular revascularization, myocardial infarction, rehospitalization due to unstable angia and heart failure, transient ischemic attack and stroke. And analysis was conducted to identify the relationships among risk factors, coronary artery disease and coronary score. Exploration was made to find the relationship between the plasma adiponectin level and the MACCE and the factors influencing prognosis.
Results
1, Among Beijing Han patients with coronary artery disease, male gender[P<0.01, OR 2.648,95%CI (1.494-4.692)],2-DM[P<0.01, OR 2.399,95%CI (1.251-4.602)], smoke[P<0.01, OR 4.441,95%CI (1.356-14.548)] are associated with coronary artery disease.
2, Compared with other classic cardiovascular risk factors, coronary artery severity degree is associated with male,2-DM and hypertension by ways of coronary score systems (P＜0.01)
3, The patients with coronary artery disease was accompanied with reduced left ventricular ejection fraction[P<0.01,95%CI (0.874-5.829)], reduced renal function[P<0.01,95%CI (5.137-17.594)], and elevated HsCRP level, which were associated with degree of coronary artery severity.
4, The risk of MACCE is associated with stenosis of coronary artery[P<0.01,95%CI (3.973-19.401)], left ventricular ejection fraction[P<0.01,95%CI (0.859-2.523)] and the level of HsCRP[P<0.01,95%CI (1.342-6.219)].
5, Plasma adiponectin level is associated with classic cardiovascular risk factors. Multiple regression analysis shows adiponectin is associated with risk of MACCE (RR=0.43, P<0.05), which is not influenced by classic cardiovascular risk factors and degree of coronary artery severity.
Conclusion
1, Among classic cardiovascular risk factors, smoke, male and 2-DM are more closed to coronary artery disease within Beijing Han. Those patients were accompanied with impaired cardiac and renal function and elevated HsCRP level, which were associated with degree of coronary artery severity.
2, Adiponectin is associated with classic cardiovascular risk factors, and it is an indepent predictor of prognosis of coronary artery disease.
据报道冠心病(coronary artery disease, CAD)患者冠心病危险因素具有民族及地区的差异性,而这些危险因素与冠状动脉病变的严重程度具有一定的相关性。近年来新发现的冠心病危险因素中,较多研究均支持低脂联素血症与冠心病及冠心病危险因素具有一定的相关性,并且脂联素具有种族特异性。
目的：
研究北京地区汉族冠心病患者的冠心病危险因素的特点及临床表现,探讨脂联素(adiponectin, APN)水平与冠心病危险因素的关系,APN和冠心病患者的主要心脑血管不良事件的关系。
材料和方法：
以2007年7月至2009年5月在北京协和医院因胸痛住院行冠脉造影检查的北京地区汉族患者为研究对象,共收集503例,对其中明确诊断冠心病的患者进行临床随访,随访截止日期2010年3月17(最长随访31月,最短1月,平均随访19月)。就诊住院当日,所有患者均收集其一般信息、冠心病危险因素以及既往患病信息等,并采集静脉血检测空腹静脉血浆葡萄糖、血脂、APN等指标,并行冠状动脉造影检查。同时评估调查对象的肌酐清除率(Creatinine clearance Ccr)、左室射血分数等临床特点,符合冠心病诊断标准的研究对象纳入随访观察,记录终点事件发生情况。终点事件主要指心脑血管主要不良事件(major adverse cardiac and cerebral vascular events, MACCE),它的具体内容包括心源性死亡、非心源性死亡、靶血管病变重建、随访期间发生的心肌梗死、脑卒中或者一过性脑缺血、需要住院治疗的不稳定心绞痛和心功能衰竭,其中不稳定心绞痛和心肌梗死并为急性冠脉综合症。分析冠心病危险因素与冠脉狭窄程度及冠脉积分的关系；探讨冠心病患者预后的影响因素及脂联素水平对冠心病患者预后的价值。
结果：
1、北京地区汉族冠心病患者人群中,男性[P＜0.01, OR=2.648,95%CI(1.494-4.692)]、2型糖尿病[P＜0.01, OR=2.399,95%CI (1.251-4.602)]、吸烟[P＜0.01, OR=4.441,95%CI (1.356-14.548)]为其冠心病主要危险因素。
2、通过冠脉积分对冠心病患者冠脉病变的严重程度与传统的心血管疾病危险因素分析得出,男性、2型糖尿病及高血压病与冠脉病变严重程度相关(P<0.01)。
3、与对照组比较,冠心病患者可以伴随左室射血功能减退[P<0.01,95%CI(0.874-5.829)],肾脏功能下降[P<0.01,95%CI(5.137-17.594)],超敏C反应蛋白(HsCRP)水平升高[P<0.01,95%CI(1.298-3.013)],而且这些参数变化与冠脉病变严重程度相关。
4、冠心病患者的MACCE发生与冠脉狭窄程度[P<0.05,95%CI(3.973-19.401)]、超声左室射血分数[P<0.01,95%CI(0.859-2.523)]及HsCRP水平[P<0.01,95%CI(1.342-6.219)]具有一定的相关性。
5、APN水平与冠心病多种危险因素具有相关性,多元回归分析显示低APN血症的冠心病患者出现MACCE的风险增高, (RR=0.43,P<0.05),且不受冠心病传统危险因素、临床特点及冠脉病变严重程度的影响。
结论：
1、在传统的冠心病危险因素中,吸烟、男性及2型糖尿病与北京地区汉族冠心病患者联系更加紧密,而且心肾功能下降和HsCRP水平升高与冠脉病变严重程度具有一定相关性。
2、低APN血症和与多个冠心病危险因素具有相关性,是冠心病患者预后的较好的预测因子。
Background
The importance of different cardiovascular risk factors varies among different countries and ethnicities, which are also associated with degree of coronary artery severity. Hypoadiponectinemia has been reported to be associated with cardiovascular disease and cardiovascular risk factors, and plasma adiponectin level is different among different ethnicities
Objective
To analyse distribution characteristics of cardiovascular risk factors and clinical characteristics within patients with coronary artery disease in Beijing Han. To explore the relationship between adiponectin level and cardiovascular risk factors, and to investigate the relationship between adiponectin and prognosis of cardiovascular diseases, especially coronary artery disease.
Design and method
A total of 503 hospitalized patients undergoing coronary angiography, who were Beijing Han, from July 2007 to May 2009 in Peking Union Medical College Hostipal were included. All patients' clinical data, including classic cardiovascular risk factors, creatinine clearance, left ventricle ejection fraction were recorded after admission and those with cardiovascular disease were followed up till March 17, 2010(1month to 31monthes). The primary end point was the combined occurrence of major adverse cardiovascular cerebral vascular events(MACCE), including cardiovascular death, non-cardiovascular death, targeted vascular revascularization, myocardial infarction, rehospitalization due to unstable angia and heart failure, transient ischemic attack and stroke. And analysis was conducted to identify the relationships among risk factors, coronary artery disease and coronary score. Exploration was made to find the relationship between the plasma adiponectin level and the MACCE and the factors influencing prognosis.
Results
1, Among Beijing Han patients with coronary artery disease, male gender[P<0.01, OR 2.648,95%CI (1.494-4.692)],2-DM[P<0.01, OR 2.399,95%CI (1.251-4.602)], smoke[P<0.01, OR 4.441,95%CI (1.356-14.548)] are associated with coronary artery disease.
2, Compared with other classic cardiovascular risk factors, coronary artery severity degree is associated with male,2-DM and hypertension by ways of coronary score systems (P＜0.01)
3, The patients with coronary artery disease was accompanied with reduced left ventricular ejection fraction[P<0.01,95%CI (0.874-5.829)], reduced renal function[P<0.01,95%CI (5.137-17.594)], and elevated HsCRP level, which were associated with degree of coronary artery severity.
4, The risk of MACCE is associated with stenosis of coronary artery[P<0.01,95%CI (3.973-19.401)], left ventricular ejection fraction[P<0.01,95%CI (0.859-2.523)] and the level of HsCRP[P<0.01,95%CI (1.342-6.219)].
5, Plasma adiponectin level is associated with classic cardiovascular risk factors. Multiple regression analysis shows adiponectin is associated with risk of MACCE (RR=0.43, P<0.05), which is not influenced by classic cardiovascular risk factors and degree of coronary artery severity.
Conclusion
1, Among classic cardiovascular risk factors, smoke, male and 2-DM are more closed to coronary artery disease within Beijing Han. Those patients were accompanied with impaired cardiac and renal function and elevated HsCRP level, which were associated with degree of coronary artery severity.
2, Adiponectin is associated with classic cardiovascular risk factors, and it is an indepent predictor of prognosis of coronary artery disease.
引文
1 Ford ES, Ajani UA, Croft JB, et al. Explaining the decrease in U.S. deaths from coronary disease,1980-2000. N Engl J Med 2007; 356(23):2388-2398,
2 Morgan TM, Krumholz HM, Lifton RP, et al. Nonvalidation of reported genetic risk factors for acute coronary syndrome in a large-scale replication study. JAMA 2007; 297(14):1551-1561.
3 Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364(9438):937-952.
4 Clendenning R. The optimal low-density lipoprotein is 50 to 70 mg/dl [letter]. J Am Coll Cardiol 2005; 45(10):1732.
5 Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Car 1983,51(3):606.
6 Reardon MF, Nestel PJ, Craig IH, et al. Lipoprotein predictors of the severity of coronary artery disease in men and women.Circulation 1985;71(5):881-888.
7 Sullivan DR, Marwick TH, Freedman SB. A new method of scoring comnary angiograms to reflect extent of coronary atherosclerosis and improve correlation with major risk factors. Am Heart J 1990,119(6):1262-1267.
8 Yusuf S, Reddy S, Ounpuu S, et al. Global burden of cardiovascular diseases, part Ⅰ: general considerations, the epidemiologic transition, risk factors, and impact of urbanization.Circulation 2001; 104(22):2746-2753.
9 Barrett-connor E, Khaw KT, Yens SC. A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med 1986,315(24):1519-1524.
10 Kambara H, Yamazaki T, Hayashi D, et al. Gender differences in patients with coronary artery disease in Japan:the Japanese Coronary Artery Disease Study (the JCAD study).Circ J 2009;73(5):912-917.
11 Marsh JD, Lehmam MH, Ritchie RH, et al. Androgen receptors mediate hypertrophy in cardiacmyocytes. Circulation 1998,98(3):256-261.
12 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.
13 Lloyd-Jones DM, Leip EP, Larson MG, et al. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation 2006; 113(6):791-798.
14 Conaway DG, O'Keefe JH, Reid KJ, et al. Frequency of undiagnosed diabetes mellitus in patients with acute coronary syndrome. Am J Cardiol 2005; 96(3):363-365.
15 Morrish NJ, Wang SL, Stevens LK, et al. Mortality and causes of death in the WHO multinational study of vascular disease in diabetes. Diabetologia 2001; 44(suppl 2):S14-S21.
16 Fava S, Azzopardi J, Muscat HA, et al. Factors that influence outcome in diabetic subjects with myocardial infarction. Diabetes Care 1993; 16(12):1615-1618.
17 Teo KK, Ounpuu S, Hawken S, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study:a case-control study. Lancet 2006; 36(9536):647-658.
18 Doll R, Peto R, Boreham J, et al. Mortality in relation to smoking:50 years' observations on male British doctors. BMJ 2004; 328(7455):1519-28.
19 Critchley JA, Capewell S. Mortality risk reduction associated with smoking cessation in patients with coronary heart disease:a systematic review. JAMA 2003; 290(1):86-97.
20 O'Keefe JH, Bell DS, Wyne KL. Diabetes Essentials.4th ed. Sudbury, MA:Jones and Bartlett Publishers; 2009:191.
21罗亚玮,陈方,张维东等。冠心病合并2型糖尿病患者冠状动脉内支架术后的远期随访。中华心血管病杂志2009；37(5)：402-405.
22 Ibebuogu UN, Nasir K, Gopal A, et al. Comparison of atherosclerotic plaque burden and composition between diabetic and non diabetic patients by non invasive CT angiography. Int J Cardiovasc Imaging 2009; 25(7):717-23.
23 Morka J, Krzeminska-Pakula M, Drozdz J, et al. Factors affecting the progression of atherosclerosis in the coronary arteries. Kardiol Pol 2007; 65(11):1307-1311; discussion 1312.
1 Reilly MP, Rader DJ. The metabolic syndrome:More than the sum of its parts? Circulation 2003; 108(13):1546-1551.
2 Friedman JM. A war on obesity, not the obese. Science 2003; 299(5608):856-858.
3 Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005; 96(9):939-949.
4 Arita Y, Kihara S, Ouchi N. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun1999; 257(1):79-83.
5 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 U S A 2001; 98(4):2005-2010.
6 Pajvani UB, Hawkins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004; 279(13):12152-12162.
7 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(4): e27-e31.
8 Waki H, Yamauchi T, Kamon J, et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003; 278(41):40352-40363.
9 Matsuzawa Y, Funahashi T, Kihara S. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 2004; 24(1):29-33.
10 Valsamakis G, Chetty R, McTernan PG, et al. Fasting serum adiponectin concentration is reduced in Indo-Asian subjects and is related to HDL cholesterol. Diabetes Obes Metab 2003; 5(2):131-135.
11 Kojima S, Funahashi T, Otsuka F, et al. Future adverse cardiac events can be predicted by persistently low plasma adiponectin concentrations in men and marked reductions of adiponectin in women after acute myocardial infarction. Atherosclerosis.2007; 194(1):204-13.
12 Huang SS, Huang PH, Chen YH, et al. Association of adiponectin with future cardiovascular events in patients after acute myocardial infarction. J Atheroscler Thromb.2010; 17(3):295-303.
13 Schnabel R, Messow CM, Lubos E, et al. Association of adiponectin with adverse outcome in coronary artery disease patients:results from the AtheroGene study. Eur Heart J.2008; 29(5):649-57.
14 Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Car.1983,51(3):606.
15 Reardon MF, Nestel PJ, Craig IH, et al. Lipoprotein predictors of the severity of coronary artery disease.Circulation.1985;71(5):881-888.
16 Sullivan DR, Marwick TH, Freedman SB. A new method of scoring comnary angiograms to reflect extent Of coronary atherosclerosis and improve correlation with major risk factors. Am Heart.1990,119(6):1262-1267.
17黎明,阴津华,高珊等。人血清脂联素竞争性酶免疫分析方法的建立及初步应用。中国糖尿病杂志2007,15(11)：693-695。
18 Ryo M, Nakamura T, Kihara S, et al. Adiponectin as a biomarker of the metabolic syndrome. Circ J 2004; 68(11):975-981.
19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。
20宁彬,马震,辛国勇等。血清脂联素水平与冠心病患者冠脉病变稳定性及狭窄程度的相关性分析。中西医结合心脑血管病杂志。2010,8(1)：25-26。
21米树华,杨秀秀,陶红等。血清脂联素水平与冠心病严重程度的关系。中国介入心脏病学杂志。2009,17(3)：160-163。
22张峻,乔树宾,杨国胜等。冠心病合并代谢综合症患者脂联素水平与炎症因子及冠状动脉病变的关系。中国循环杂志2008,23(2)：102-105。
23李湘,高鑫,张斌等。脂联素与非糖尿病男性冠心病代谢危险因素的相关性研究。中华医学杂志。2007,87(28)：1971-1974。
24 Nishizawa H, Shimomura I, Kishida K, et al. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes.2002; 51(9): 2734-2741.
25 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(18):18073-18080.
26 Arita Y, Kihara S, Ouchi N. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun.1999; 257(1):79-83.
27 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.
28 Yatagai T, Nagasaka S, Taniguchi A, et al. Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 dia-betes mellitus. Metabolism.2003; 52(10):1274-1278.
29 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.
30 Monzillo LU, Hamdy O, Horton ES. Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance. Obes Res.2003; 11 (9):1048-1054.
31 Yang WS, Lee WJ, Funahashi T, et al. Plasma adiponectin levels in overweight and obese Asians. Obes Res.2002; 10(11):1104-1110.
32 Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab.2002; 87(6): 2764-2769.
33 Huang KC, Lue BH, Yen RF, et al. Plasma adiponectin levels and metabolic factors in nondiabetic adolescents. Obes Res.2004; 12(1):119-124.
34 Schulze MB, Rimm EB, Shai I, et al. Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes. Diabetes Care.2004; 27(7):1680-1687.
35 Kazumi T, Kawaguchi A, Hirano T, et al. Serum adiponectin is associated with high-density lipoprotein cholesterol, triglycerides, and low-density lipoprotein particle size in young healthy men. Metabolism.2004; 53(5):589-593.
36 Komura N, Kihara S, Sonoda M, et al. Increment and impairment of adiponectin in renal failure.Cardiovasc Res.2010; 86(3):471-477.
37 Ouchi N, Kihara S, Arita Y, et al. Adiponectin, adipocyte-derived protein, inhibits endothelial NFkB signaling through cAMPdependent pathway. Circulation.2000; 102(11):1296-1301.
38 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.
39 Wolk R, Berger P, Lennon RJ, et al. Association between plasma adiponectin levels and unstable coronary syndromes. Eur Heart J.2007; 28(3):292-298.
40 Liang KW, Sheu WH, Lee WL, et al. Decreased circulating protective adiponectin level is associated with angiographic coronary disease progression in patients with angina pectoris. Int J Cardiol.2008 16; 129(1):76-80.
41 Pischon T, Girman CJ, Hotamisligil GS, et al. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA.2004; 291(14):1730-1737.
42 Schulze MB, Shai I, Rimm EB, et al. Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes.2005; 54(2):534-539.
43 Frystyk J, Berne C, Berglund L, et al. Serum adiponectin is a predictor of coronary heart disease:a population-based 10-year follow-up study in elderly men. J Clin Endocrinol Metab.2007; 92(2):571-576.
44 Chen H, Montagnani M, Funahashi T, et al. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem.2003; 278(45):45021-45026.
45 Xu SQ, Mahadev K, Wu X, et al. Adiponectin protects against angiotensin Ⅱ or tumor necrosis factor a-induced endothelial cell monolayer hyperpermeability:role of cAMP/PKA signaling. Arterioscler Thromb Vase Biol.2008(5); 28:899-905.
46 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(8):1057-1063.
47 Ouchi N, Kobayashi H, Kihara S, et al. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem.2004; 279(2):1304-1309.
48 Hattori Y, Suzuki M, Hattori S, et al. Globular adiponectin upregulates nitric oxide production in vascular endothelial cells. Diabetologia 2003; 46(11):1543-1549
49 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.
50 Fasshauer M, Kralisch S, Klier M, et al. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun.2003; 301(4):1045-1050.
51 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. Circ Res.2008; 102(2):218-225.
52 Wang Y, Lam KS, Xu JY, et al. Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem.2005; 280(18):18341-18347.
53 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.
54 Esposito K, Pontillo A, Di Palo C, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women; a randomized trial. JAMA. 2003; 289(14):1799-1804.
55 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.
56 Bora PS, et al. Expression of adiponectin in choroidal tissue and inhibition of laser induced choroidal neovascularization by adiponectin. FEBS Lett.2007; 581(10): 1977-1982.
57 Tao L, Gao E, Jiao X, et al. adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation.2007; 115(11):1408-1416.
1. Reilly MP, Rader DJ. The metabolic syndrome:More than the sum of its parts? Circulation.2003; 108(13):1546-1551.
2. Friedman JM. A war on obesity, not the obese. Science.2003; 299(5608):856-858.
3. Hampton T. Scientists study fat as endocrine organ. JAMA.2006; 296(13): 1573-1575.
4. Fujioka S, Matsuzawa Y, Tokunaga K, et al. Contribution of intraabdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism.1987; 36(1):54-59.
5. Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res.2005; 96(9):939-949.
6. Han SH, Quon MJ, Kim J. Adiponectin and cardiovascular disease:response to therapeutic interventions. J Am Coll Cardiol.2007; 49(5):531-538.
7. Ryo M, Nakamura T, Kihara S, et al. Adiponectin as a biomarker of the metabolic syndrome. Circ J.2004; 68(11):975-981.
8. Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to c 1 q, produced exclusively in adipocytes. J Biol Chem.1995; 270(45):26746-26749.
9. Maeda K, Okubo K, Shimomura I, et al. Cdna cloning and expression of a novel adipose specific collagen-like factor, apml (adipose most abundant gene transcript 1). Biochem Biophys Res Commun.1996; 221(2):286-289.
10. Hu E, Liang P, Spiegelman BM. Adipoq is a novel adipose-specific gene dysregulated in obesity. J Biol Chem.1996; 271 (18):10697-703.
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; 120(4): 803-812.
12. Leinninger GM, Myers MG Jr. Lrb signals act within a distributed network of leptin-responsive neurones to mediate leptin action. Acta Physiol (Oxf).2008; 192(1):49-59.
13. Stumvoll M, Tschritter O, Fritsche A, et al. Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity:interaction with family history of type 2 diabetes. Diabetes.2002; 51(1):37-41.
14. 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 U S A.2001; 98:2005-2010.
15. Wang Y, et al. Hydroxylation and glycosylation of the four conserved lysine residues in the collagenous domain of adiponectin. Potential role in the modulation of its insulin-sensitizing activity. J Biol Chem 2002; 277: 19521-19529.
16. Magkos F, Sidossis LS. Recent advances in the measurement of adiponectin isoform distribution. Curr Opin Clin Nutr Metab Care 2007; 10:571-575.
17.Pajvani UB, Hawkins M, Combs TP, et al:Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004; 279:12152-12162.
18. Waki H, Yamauchi T, Kamon J, et al:Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003; 278:40352-40363.
19. Tsao TS, Tomas E, Murrey HE, et al:Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways. J Biol Chem 2003; 278:50810-50817.
20. 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:e27-e31.
21. Waki H, Yamauchi T, Kamon J, et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003; 278:40352-40363.
22. Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003; 423:762-769.
23. Motoshima H, et al. Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. Biochem Biophys Res Commun 2004; 315:264-271.
24. Ding G, et al. Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor. J Mol Cell Cardiol 2007; 43:73-84.
25. 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.
26. 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: E1836-44.
27. 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.
28. Arita Y, Kihara S, Ouchi N:Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun1999; 257:79-83.
29. Matsuzawa Y, Funahashi T, Kihara S:Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 2004; 24:29-33.
30. Valsamakis G, Chetty R, McTernan PG, et al:Fasting serum adiponectin concentration is reduced in Indo-Asian subjects and is related to HDL cholesterol. Diabetes Obes Metab 2003; 5:131-135.
31. 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; 87:5662-5667.
32. Maeda N, Takahashi M, Funahashi T, et al:PPARy ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes2001; 50:2094-2099.
33. Kim JA, Montagnani M, Koh KK, et al:Reciprocal relationships between insulin resistance and endothelial dysfunction:molecular and pathophysiological mechanisms. Circulation 2006; 113:1888-1904.
34. Ouchi N, Kihara S, Arita Y, et al:Novel modulator for endothelial adhesion molecules:adipocyte-derived plasma protein. Circulation 1999; 100:2473-2476.
35. Ouchi N, Kihara S, Arita Y, et al:Adiponectin, adipocyte-derived protein, inhibits endothelial NFkB signaling through cAMPdependent pathway. Circulation 2000; 102:1296-1301.
36. Xu SQ, Mahadev K, Wu X, et al:Adiponectin protects against angiotensin Ⅱ or tumor necrosis factor a-induced endothelial cell monolayer hyperpermeability:role of cAMP/PKA signaling. Arterioscler Thromb Vasc Biol 2008; 28:899-905.
37. 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.
38. Hattori Y, Suzuki M, Hattori S, Kasai K. Globular adiponectin upregulates nitric oxide production in vascular endothelial cells. Diabetologia.2003; 46:1543-1549.
39. Ouchi N, Kobayashi H, Kihara S, Kumada M, Sato K, Inoue T, et al. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem 2004; 279:1304-1309.
40. Ouedraogo R, et al. Adiponectin suppression of high-glucose-induced reactive oxygen species in vascular endothelial cells:evidence for involvement of a cAMP signaling pathway. Diabetes 2006; 55:1840-1846.
41. Ouchi N, Ohishi M, Kihara S, et al:Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension 2003; 42:231-234.
42. Nishimura M, Izumiva Y, Hiquchi A, et al:Adiponectin prevents cerebral ischemic injury through endothelial nitric oxide synthase dependent mechanisms. Circulation 2008; 117:216-223.
43. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 2002; 106:2767-2770.
44. Okamoto Y, Folco EJ, Minami M, Wara AK, Feinberg MW, Sukhova GK, et al. Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Circ Res 2008; 102:218-225.
45. Fasshauer M, Kralisch S, Klier M, et al:Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2003; 301:1045-1050.
46. Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, et al. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 2004; 109:2046-2049.
47. Furukawa K, Hori M, Ouchi N, et al:Adiponectin down-regulates acylcoenzyme A:cholesterol acyltransferasea in cultured human monocyte-derived macrophages. Biochem biophys Res Commun 2004;317:831-836.
48. Takemura Y, Ouchi N, Shibata R, Aprahamian T, Kirber MT, Summer RS, et al. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest 2007; 117:375-386.
49. 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; 105:2893-2898.
50. Wang Y, Lam KS, XuJY, et al:Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerizationdependent manner. J Biol Chem 2005; 280:18341-18347.
51. 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.
52. 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.
53. Ouedraogo R, et al. Adiponectin deficiency increases leukocyte-endothelium interactions via upregulation of endothelial cell adhesion molecules in vivo. J Clin Invest 2007; 117:1718-1726.
54. 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.
55. Esposito K, Pontillo A, Di Palo C, et al:Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women; a randomized trial. JAMA 2003; 289:1799-1804.
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 Vasc Biol 2008; 28:1368-1374.
57. Kobashi C, Urakaze M, Kishida M, Kibayashi E, Kobayashi H, Kihara S, et al. Adiponectin inhibits endothelial synthesis of interleukin-8. Circ Res 2005; 97: 1245-1252.
58. Natarajan R, et al. Hypoxia inducible factor-1 upregulates adiponectin in diabetic mouse hearts and attenuates post-ischemic injury. J Cardiovasc Pharmacol 2008; 51:178-187.
59. Zhang H, Zhang C. Regulation of microvascular function by adipose tissue in obesity and type 2 diabetes:evidence of an adipose-vacular loop. Am J Biomed sci 2009; 1:133-142
60. Date H, et al. Adiponectin produced in coronary circulation regulates coronary flow reserve in nondiabetic patients with angiographically normal coronary arteries. Clin Cardiol 2006; 29:211-214.
61. Bora PS, et al. Expression of adiponectin in choroidal tissue and inhibition of laser induced choroidal neovascularization by adiponectin. FEBS Lett 2007; 58: 1977-1982.
62. Mahadev K, et al. Adiponectin inhibits vascular endothelial growth factor-induced migration of human coronary artery endothelial cells. Cardiovasc Res 2008; 78:376-384.
63. Braakenhielm E, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspasemediated endothelial cell apoptosis. Proc Natl Acad Sci USA 2004; 101:2476-2481.
64. Frystyk J, et al. Increased serum adiponectin levels in type 1 diabetic patients with microvascular complications. Diabetologia 2005; 48:1911-1918.
65. Schalkwijk CG, et al. Adiponectin is inversely associated with renal function in Type 1 diabetic patients. J Clin Endocrinol Metab 2005; 91:129-135.
66. 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; 46:459-469.
67. Yatagai T, Nagasaka S, Taniguchi A, et al. Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 dia-betes mellitus. Metabolism 2003; 52:1274-1278.
68. 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.
69. 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; 73:534-539.
70. Vozarova B, Stefan N, Lindsay RS, et al. Low plasma adiponectin concentrations do not predict weight gain in humans. Diabetes 2002; 51:2964-2967.
71. Hulver MW, Zheng D, Tanner CJ, et al. Adiponectin is not altered with exercise training despite enhanced insulin action. Am J Physiol Endocrinol Metab 2002; 283:E861-E865.
72. Yatagai T, Nishida Y, Nagasaka S, et al. Relationship between exercise training-induced increase in insulin sensitivity and adiponectinemia in healthy men. Endocr J 2003; 50:233-238.
73. Valsamakis G, McTernan PQ Chetty R, et al. Modest weight loss and reduction in waist circumference after medical treatment are associated with favorable changes in serum adipocytokines. Metabolism 2004; 53:430-434.
74. Despres JP, Golay A, Sjostrom L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005; 353:2121-2134.
75. Calvani M, Scarfone A, Granato L, et al. Restoration of adiponectin pulsatility in severely obese subjects after weight loss. Diabetes 2004; 53:939-947.
76. Nakatani H, Hirose H, Yamamoto Y, et al. Significance of leptin and high-molecular weight adiponectin in the general population of Japanese male adolescents. Metabolism 2008; 57:157-162.
77. Kaser S, Tatarczyk T, Stadlmayr A, et al. Effect of obesity and insulin sensitivity on adiponectin isoform distribution. Eur J Clin Invest 2008; 38:827-34.
78. 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; 89:663.
79. Monzillo LU, Hamdy O, Horton ES:Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance. Obes Res 2003; 11:1048-1054.
80. 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;86:1930-1935.
81. 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.
82. 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.
83. Snehalatha C, Mukesh B, Simon M, et al. Plasma adiponectin is an independent predictor of type 2 diabetes in Asian Indians. Diabetes Care 2003; 26:3226-3229.
84. Stefan N, Vozarova B, Funahashi T, et al. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes 2002; 51:1884-1888.
85. Yamamoto Y, Hirose H, Saito I, et al. Adiponectin, an adipocyte-derived protein, predicts future insulin resistance:two-year follow-up study in Japanese population. J Clin Endocrinol Metab 2004; 89:87-90.
86. Duncan BB, Schmidt MI, Pankow JS, et al. Adiponectin and the development of type 2 diabetes:the atherosclerosis risk in communities study. Diabetes 2004; 53:2473-8.
87. 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;29:1357-1362
88. Nakashima R, Kamei N, Yamane K, et al. Decreased total and high molecular weight adiponectin are independent risk factors for the development of type 2 diabetes in Japanese-Americans. J Clin Endocrinol Metab 2006; 91:3873-3877.
89. Basu R, Pajvani UB, Rizza RA, et al. Selective downregulation of the high-molecular weight form of adiponectin in hyperinsulinemia and in type 2 diabetes. Differential regulation from nondiabetic subjects. Diabetes 2007; 56:2174-2177.
90. Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000; 20:1595-1599.
91. Tonelli J, Li W, Kishore P, et al. Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes. Diabetes 2004; 53:1621-1629.
92. Qurashi S, Mynarcik DC, McNurlan MA, et al. Importance of the high-molecular-mass isoform of adiponectin in improved insulin sensitivity with rosiglitazone treatment in HIV disease. Clin Sci (Lond) 2008; 115:197-202.
93. Yang WS, Lee WJ, Funahashi T, et al. Plasma adiponectin levels in overweight and obese Asians. Obes Res 2002; 10:1104-1110.
94. Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 2002; 87:2764-2769.
95. Huang KC, Lue BH, Yen RF, et al. Plasma adiponectin levels and metabolic factors in nondiabetic adolescents. Obes Res 2004; 12:119-124
96. Fruebis J, Tsao TS, Javorschi S, et al. Proteolytic cleavage product of 30-kda adipocyte complement-related proteinincreases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001; 98:2005-2010.
97. Schulze MB, Rimm EB, Shai Ⅰ, et al. Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes. Diabetes Care 2004; 27:1680-1687.
98. Kazumi T, Kawaguchi A, Hirano T, et al. Serum adiponectin is associated with high-density lipoprotein cholesterol, triglycerides, and low-density lipoprotein particle size in young healthy men. Metabolism 2004; 53:589-593.
99. Lara-Castro C, Luo N, Wallace P, et al. Adiponectin multimeric complexes and the metabolic syndrome trait cluster. Diabetes 2006; 55:249-259.
100. Lautamaki R, et al. Low serum adiponectin is associated with high circulating oxidized low-density lipoprotein in patients with type 2 diabetes mellitus and coronary artery disease. Metabolism 2007; 56:881-886.
101. Koh KK, Quon MJ, Han SH, et al. Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients. Circulation 2004; 110:3687-3692.
102. Bayes B, Granada ML, Lauzurica R, et al. Effect of low doses of atorvastatin on adiponectin, glucose homeostasis, and clinical inflammatory markers in kidney transplant recipients. Transplant Proc 2005; 37:3808-3812.
103. Gannage-Yared MH, Azar RR, Amm-Azar M, et al. Pravastatin does not affect insulin sensitivity and adipocytokines levels in healthy nondiabetic patients. Metabolism 2005;54:947-951.
104. Sonmez A, Dogru T, Tasci I, et al. The effect of fluvastatin on plasma adiponectin levels in dyslipidaemia. Clin Endocrinol (Oxf) 2006; 64:567-572.
105. Kazumi T, Kawaguchi A, Sakai K, et al. Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure. Diabetes Care 2002; 25:971-976.
106. Dzielinska Z, Januszewicz A, Wiecek A, et al. Decreased plasma concentration of a novel anti-inflammatory protein-adiponectin-in hypertensive men with coro-nary artery disease. Thromb Res 2003; 110:365-369.
107. Adamczak M, Wiecek A, Funahashi T, et al. Decreased plasma adiponectin concentration in patients with essential hypertension. Am J Hypertens 2003; 16:72-75.
108. Ohashi K, Kihara S, Ouchi N, et al. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension 2006; 47:1108-1116.
109. Shibata R, Ouchi N, Ito M, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med 2004; 10:1384-1389.
110. Chow WS, Cheung BM, Tso AW, et al. Hypoadiponectinemia as a predictor for the development of hypertension:a 5-year prospective study. Hypertension 2007; 49:1455-1461.
111. Koh KK, Quon MJ, Han SH, et al. Distinct vascular and metabolic effects of different classes of anti-hypertensive drugs. Int J Cardiol 2008 Dec 5. [Epub ahead of print]
112. Yilmaz MI, Sonmez A, Caglar K, et al. Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome. Nephrology (Carlton) 2007; 12:147-153.
113. Wolk R, Berger P, Lennon RJ, Brilakis ES, Somers VK. Body mass index:a risk factor for unstable angina and myocardial infarction in patients with angiographically confirmed coronary artery disease. Circulation. 2003; 108:2206-2211
114. Orlander PR, Goff DC, Morrissey M, Ramsey DJ, Wear ML, Labarthe DR, Nichaman MZ. The relation of diabetes to the severity of acute myocardial infarction and post-myocardial infarction survival in Mexican-Americans and non-Hispanic whites. The Corpus Christi Heart Project. Diabetes.1994; 43:897-902.
115. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, Funahashi T, Ouchi N, Walsh K. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK-and COX-2-dependent mechanisms. Nat Med.2005; 11:1096-1103.
116. Pischon T, Girman CJ, Hotamisligil GS, et al:Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004; 291:1730-1737.
117. Schulze MB, Shai I, Rimm EB, et al:Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes 2005; 54:534-539.
118. Kojima S, Funahashi T, Otsuka F, Maruyoshi H, Yamashita T, Kajiwara I, et al. Future adverse cardiac events can be predicted by persistently low plasma adiponectin concentrations in men and marked reductions of adiponectin in women after acute myocardial infarction. Atherosclerosis 2002; 194:204-213.
119. 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; 90:5677-5683.
120. Nakamura Y, Shimada K, Fukuda D, et al:Implications of plasma concentrations of adiponectin in patients with coronary artery disease. Heart 2004; 90:528-533.
121. Wolk R, Berger P, Lennon RJ, et al:Association between plasma adiponectin levels and unstable coronary syndromes. Eur Heart J 2007; 28:292-298.
122. Zoccali C, Mallamaci F, Tripepi G:Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 2002; 13:134-141.
123. 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; 90:5677-83.
124. Soderberg S, Colquhoun D, Keech A, et al. Leptin, but not adiponectin, is a predictor of recurrent cardiovascular events in men:results from the lipid study. Int J Obes (Lond) 2009; 33:123-30.
125. Sattar N, Wannamethee Q Sarwar N, et al. Adiponectin and coronary heart disease:a prospective study and meta-analysis. Circulation 2006; 114:623-629.
126. Kistorp C, Faber J, Galatius S, et al. Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation 2005; 112:1756-1762.
127. Tamura T, Furukawa Y, Taniguchi R, et al. Serum adiponectin level as an independent predictor of mortality in patients with congestive heart failure. Circ J 2007;71:623-63 0.
128. Norrelund H, Wiggers H, Halbirk M, et al. Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failure. J Intern Med 2006; 260:11-21.
129. McEntegart MB, Awede B, Petrie MC, et al. Increase in serum adiponectin concentration in patients with heart failure and cachexia:relationship with leptin, other cytokines, and b-type natriuretic peptide. Eur Heart J 2007; 28:829-35.
130. 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; 28:1723-30.
131. Anker SD, Rauchhaus M. Insights into the pathogenesis of chronic heart failure: Immune activation and cachexia. Curr Opin Cardiol 1999; 14:211-216.
132. Ingelsson E, Riserus U, Berne C, Frystyk J, Flyvbjerg A, Axelsson T, et al. Adiponectin and risk of congestive heart failure. JAMA 2006; 295:1772-1774.
133. Lin HV, Kim JY, Pocai A, Rossetti L, Shapiro L, Scherer PE, et al. Adiponectin resistance exacerbates insulin resistance in insulin receptor transgenic/knockout mice. Diabetes 2007; 56:1969-1976.
134. Mullen KL, Pritchard J, Ritchie I, Snook LA, Chabowski A, Bonen A, et al. Adiponectin resistance precedes the accumulation of skeletal muscle lipids and insulin resistance in high fat fed rats. Am J Physiol Regul Integr Comp Physiol 2008; 296:R243-R251.
2 Morgan TM, Krumholz HM, Lifton RP, et al. Nonvalidation of reported genetic risk factors for acute coronary syndrome in a large-scale replication study. JAMA 2007; 297(14):1551-1561.
3 Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364(9438):937-952.
4 Clendenning R. The optimal low-density lipoprotein is 50 to 70 mg/dl [letter]. J Am Coll Cardiol 2005; 45(10):1732.
5 Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Car 1983,51(3):606.
6 Reardon MF, Nestel PJ, Craig IH, et al. Lipoprotein predictors of the severity of coronary artery disease in men and women.Circulation 1985;71(5):881-888.
7 Sullivan DR, Marwick TH, Freedman SB. A new method of scoring comnary angiograms to reflect extent of coronary atherosclerosis and improve correlation with major risk factors. Am Heart J 1990,119(6):1262-1267.
8 Yusuf S, Reddy S, Ounpuu S, et al. Global burden of cardiovascular diseases, part Ⅰ: general considerations, the epidemiologic transition, risk factors, and impact of urbanization.Circulation 2001; 104(22):2746-2753.
9 Barrett-connor E, Khaw KT, Yens SC. A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med 1986,315(24):1519-1524.
10 Kambara H, Yamazaki T, Hayashi D, et al. Gender differences in patients with coronary artery disease in Japan:the Japanese Coronary Artery Disease Study (the JCAD study).Circ J 2009;73(5):912-917.
11 Marsh JD, Lehmam MH, Ritchie RH, et al. Androgen receptors mediate hypertrophy in cardiacmyocytes. Circulation 1998,98(3):256-261.
12 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.
13 Lloyd-Jones DM, Leip EP, Larson MG, et al. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation 2006; 113(6):791-798.
14 Conaway DG, O'Keefe JH, Reid KJ, et al. Frequency of undiagnosed diabetes mellitus in patients with acute coronary syndrome. Am J Cardiol 2005; 96(3):363-365.
15 Morrish NJ, Wang SL, Stevens LK, et al. Mortality and causes of death in the WHO multinational study of vascular disease in diabetes. Diabetologia 2001; 44(suppl 2):S14-S21.
16 Fava S, Azzopardi J, Muscat HA, et al. Factors that influence outcome in diabetic subjects with myocardial infarction. Diabetes Care 1993; 16(12):1615-1618.
17 Teo KK, Ounpuu S, Hawken S, et al. Tobacco use and risk of myocardial infarction in 52 countries in the INTERHEART study:a case-control study. Lancet 2006; 36(9536):647-658.
18 Doll R, Peto R, Boreham J, et al. Mortality in relation to smoking:50 years' observations on male British doctors. BMJ 2004; 328(7455):1519-28.
19 Critchley JA, Capewell S. Mortality risk reduction associated with smoking cessation in patients with coronary heart disease:a systematic review. JAMA 2003; 290(1):86-97.
20 O'Keefe JH, Bell DS, Wyne KL. Diabetes Essentials.4th ed. Sudbury, MA:Jones and Bartlett Publishers; 2009:191.
21罗亚玮,陈方,张维东等。冠心病合并2型糖尿病患者冠状动脉内支架术后的远期随访。中华心血管病杂志2009；37(5)：402-405.
22 Ibebuogu UN, Nasir K, Gopal A, et al. Comparison of atherosclerotic plaque burden and composition between diabetic and non diabetic patients by non invasive CT angiography. Int J Cardiovasc Imaging 2009; 25(7):717-23.
23 Morka J, Krzeminska-Pakula M, Drozdz J, et al. Factors affecting the progression of atherosclerosis in the coronary arteries. Kardiol Pol 2007; 65(11):1307-1311; discussion 1312.
1 Reilly MP, Rader DJ. The metabolic syndrome:More than the sum of its parts? Circulation 2003; 108(13):1546-1551.
2 Friedman JM. A war on obesity, not the obese. Science 2003; 299(5608):856-858.
3 Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005; 96(9):939-949.
4 Arita Y, Kihara S, Ouchi N. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun1999; 257(1):79-83.
5 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 U S A 2001; 98(4):2005-2010.
6 Pajvani UB, Hawkins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004; 279(13):12152-12162.
7 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(4): e27-e31.
8 Waki H, Yamauchi T, Kamon J, et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003; 278(41):40352-40363.
9 Matsuzawa Y, Funahashi T, Kihara S. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 2004; 24(1):29-33.
10 Valsamakis G, Chetty R, McTernan PG, et al. Fasting serum adiponectin concentration is reduced in Indo-Asian subjects and is related to HDL cholesterol. Diabetes Obes Metab 2003; 5(2):131-135.
11 Kojima S, Funahashi T, Otsuka F, et al. Future adverse cardiac events can be predicted by persistently low plasma adiponectin concentrations in men and marked reductions of adiponectin in women after acute myocardial infarction. Atherosclerosis.2007; 194(1):204-13.
12 Huang SS, Huang PH, Chen YH, et al. Association of adiponectin with future cardiovascular events in patients after acute myocardial infarction. J Atheroscler Thromb.2010; 17(3):295-303.
13 Schnabel R, Messow CM, Lubos E, et al. Association of adiponectin with adverse outcome in coronary artery disease patients:results from the AtheroGene study. Eur Heart J.2008; 29(5):649-57.
14 Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Car.1983,51(3):606.
15 Reardon MF, Nestel PJ, Craig IH, et al. Lipoprotein predictors of the severity of coronary artery disease.Circulation.1985;71(5):881-888.
16 Sullivan DR, Marwick TH, Freedman SB. A new method of scoring comnary angiograms to reflect extent Of coronary atherosclerosis and improve correlation with major risk factors. Am Heart.1990,119(6):1262-1267.
17黎明,阴津华,高珊等。人血清脂联素竞争性酶免疫分析方法的建立及初步应用。中国糖尿病杂志2007,15(11)：693-695。
18 Ryo M, Nakamura T, Kihara S, et al. Adiponectin as a biomarker of the metabolic syndrome. Circ J 2004; 68(11):975-981.
19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。
20宁彬,马震,辛国勇等。血清脂联素水平与冠心病患者冠脉病变稳定性及狭窄程度的相关性分析。中西医结合心脑血管病杂志。2010,8(1)：25-26。
21米树华,杨秀秀,陶红等。血清脂联素水平与冠心病严重程度的关系。中国介入心脏病学杂志。2009,17(3)：160-163。
22张峻,乔树宾,杨国胜等。冠心病合并代谢综合症患者脂联素水平与炎症因子及冠状动脉病变的关系。中国循环杂志2008,23(2)：102-105。
23李湘,高鑫,张斌等。脂联素与非糖尿病男性冠心病代谢危险因素的相关性研究。中华医学杂志。2007,87(28)：1971-1974。
24 Nishizawa H, Shimomura I, Kishida K, et al. Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes.2002; 51(9): 2734-2741.
25 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(18):18073-18080.
26 Arita Y, Kihara S, Ouchi N. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun.1999; 257(1):79-83.
27 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.
28 Yatagai T, Nagasaka S, Taniguchi A, et al. Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 dia-betes mellitus. Metabolism.2003; 52(10):1274-1278.
29 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.
30 Monzillo LU, Hamdy O, Horton ES. Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance. Obes Res.2003; 11 (9):1048-1054.
31 Yang WS, Lee WJ, Funahashi T, et al. Plasma adiponectin levels in overweight and obese Asians. Obes Res.2002; 10(11):1104-1110.
32 Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab.2002; 87(6): 2764-2769.
33 Huang KC, Lue BH, Yen RF, et al. Plasma adiponectin levels and metabolic factors in nondiabetic adolescents. Obes Res.2004; 12(1):119-124.
34 Schulze MB, Rimm EB, Shai I, et al. Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes. Diabetes Care.2004; 27(7):1680-1687.
35 Kazumi T, Kawaguchi A, Hirano T, et al. Serum adiponectin is associated with high-density lipoprotein cholesterol, triglycerides, and low-density lipoprotein particle size in young healthy men. Metabolism.2004; 53(5):589-593.
36 Komura N, Kihara S, Sonoda M, et al. Increment and impairment of adiponectin in renal failure.Cardiovasc Res.2010; 86(3):471-477.
37 Ouchi N, Kihara S, Arita Y, et al. Adiponectin, adipocyte-derived protein, inhibits endothelial NFkB signaling through cAMPdependent pathway. Circulation.2000; 102(11):1296-1301.
38 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.
39 Wolk R, Berger P, Lennon RJ, et al. Association between plasma adiponectin levels and unstable coronary syndromes. Eur Heart J.2007; 28(3):292-298.
40 Liang KW, Sheu WH, Lee WL, et al. Decreased circulating protective adiponectin level is associated with angiographic coronary disease progression in patients with angina pectoris. Int J Cardiol.2008 16; 129(1):76-80.
41 Pischon T, Girman CJ, Hotamisligil GS, et al. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA.2004; 291(14):1730-1737.
42 Schulze MB, Shai I, Rimm EB, et al. Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes.2005; 54(2):534-539.
43 Frystyk J, Berne C, Berglund L, et al. Serum adiponectin is a predictor of coronary heart disease:a population-based 10-year follow-up study in elderly men. J Clin Endocrinol Metab.2007; 92(2):571-576.
44 Chen H, Montagnani M, Funahashi T, et al. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem.2003; 278(45):45021-45026.
45 Xu SQ, Mahadev K, Wu X, et al. Adiponectin protects against angiotensin Ⅱ or tumor necrosis factor a-induced endothelial cell monolayer hyperpermeability:role of cAMP/PKA signaling. Arterioscler Thromb Vase Biol.2008(5); 28:899-905.
46 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(8):1057-1063.
47 Ouchi N, Kobayashi H, Kihara S, et al. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem.2004; 279(2):1304-1309.
48 Hattori Y, Suzuki M, Hattori S, et al. Globular adiponectin upregulates nitric oxide production in vascular endothelial cells. Diabetologia 2003; 46(11):1543-1549
49 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.
50 Fasshauer M, Kralisch S, Klier M, et al. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun.2003; 301(4):1045-1050.
51 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. Circ Res.2008; 102(2):218-225.
52 Wang Y, Lam KS, Xu JY, et al. Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. J Biol Chem.2005; 280(18):18341-18347.
53 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.
54 Esposito K, Pontillo A, Di Palo C, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women; a randomized trial. JAMA. 2003; 289(14):1799-1804.
55 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.
56 Bora PS, et al. Expression of adiponectin in choroidal tissue and inhibition of laser induced choroidal neovascularization by adiponectin. FEBS Lett.2007; 581(10): 1977-1982.
57 Tao L, Gao E, Jiao X, et al. adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress. Circulation.2007; 115(11):1408-1416.
1. Reilly MP, Rader DJ. The metabolic syndrome:More than the sum of its parts? Circulation.2003; 108(13):1546-1551.
2. Friedman JM. A war on obesity, not the obese. Science.2003; 299(5608):856-858.
3. Hampton T. Scientists study fat as endocrine organ. JAMA.2006; 296(13): 1573-1575.
4. Fujioka S, Matsuzawa Y, Tokunaga K, et al. Contribution of intraabdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism.1987; 36(1):54-59.
5. Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res.2005; 96(9):939-949.
6. Han SH, Quon MJ, Kim J. Adiponectin and cardiovascular disease:response to therapeutic interventions. J Am Coll Cardiol.2007; 49(5):531-538.
7. Ryo M, Nakamura T, Kihara S, et al. Adiponectin as a biomarker of the metabolic syndrome. Circ J.2004; 68(11):975-981.
8. Scherer PE, Williams S, Fogliano M, et al. A novel serum protein similar to c 1 q, produced exclusively in adipocytes. J Biol Chem.1995; 270(45):26746-26749.
9. Maeda K, Okubo K, Shimomura I, et al. Cdna cloning and expression of a novel adipose specific collagen-like factor, apml (adipose most abundant gene transcript 1). Biochem Biophys Res Commun.1996; 221(2):286-289.
10. Hu E, Liang P, Spiegelman BM. Adipoq is a novel adipose-specific gene dysregulated in obesity. J Biol Chem.1996; 271 (18):10697-703.
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; 120(4): 803-812.
12. Leinninger GM, Myers MG Jr. Lrb signals act within a distributed network of leptin-responsive neurones to mediate leptin action. Acta Physiol (Oxf).2008; 192(1):49-59.
13. Stumvoll M, Tschritter O, Fritsche A, et al. Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity:interaction with family history of type 2 diabetes. Diabetes.2002; 51(1):37-41.
14. 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 U S A.2001; 98:2005-2010.
15. Wang Y, et al. Hydroxylation and glycosylation of the four conserved lysine residues in the collagenous domain of adiponectin. Potential role in the modulation of its insulin-sensitizing activity. J Biol Chem 2002; 277: 19521-19529.
16. Magkos F, Sidossis LS. Recent advances in the measurement of adiponectin isoform distribution. Curr Opin Clin Nutr Metab Care 2007; 10:571-575.
17.Pajvani UB, Hawkins M, Combs TP, et al:Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004; 279:12152-12162.
18. Waki H, Yamauchi T, Kamon J, et al:Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003; 278:40352-40363.
19. Tsao TS, Tomas E, Murrey HE, et al:Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different oligomers activate different signal transduction pathways. J Biol Chem 2003; 278:50810-50817.
20. 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:e27-e31.
21. Waki H, Yamauchi T, Kamon J, et al. Impaired multimerization of human adiponectin mutants associated with diabetes. Molecular structure and multimer formation of adiponectin. J Biol Chem 2003; 278:40352-40363.
22. Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003; 423:762-769.
23. Motoshima H, et al. Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL. Biochem Biophys Res Commun 2004; 315:264-271.
24. Ding G, et al. Adiponectin and its receptors are expressed in adult ventricular cardiomyocytes and upregulated by activation of peroxisome proliferator-activated receptor. J Mol Cell Cardiol 2007; 43:73-84.
25. 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.
26. 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: E1836-44.
27. 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.
28. Arita Y, Kihara S, Ouchi N:Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun1999; 257:79-83.
29. Matsuzawa Y, Funahashi T, Kihara S:Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 2004; 24:29-33.
30. Valsamakis G, Chetty R, McTernan PG, et al:Fasting serum adiponectin concentration is reduced in Indo-Asian subjects and is related to HDL cholesterol. Diabetes Obes Metab 2003; 5:131-135.
31. 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; 87:5662-5667.
32. Maeda N, Takahashi M, Funahashi T, et al:PPARy ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes2001; 50:2094-2099.
33. Kim JA, Montagnani M, Koh KK, et al:Reciprocal relationships between insulin resistance and endothelial dysfunction:molecular and pathophysiological mechanisms. Circulation 2006; 113:1888-1904.
34. Ouchi N, Kihara S, Arita Y, et al:Novel modulator for endothelial adhesion molecules:adipocyte-derived plasma protein. Circulation 1999; 100:2473-2476.
35. Ouchi N, Kihara S, Arita Y, et al:Adiponectin, adipocyte-derived protein, inhibits endothelial NFkB signaling through cAMPdependent pathway. Circulation 2000; 102:1296-1301.
36. Xu SQ, Mahadev K, Wu X, et al:Adiponectin protects against angiotensin Ⅱ or tumor necrosis factor a-induced endothelial cell monolayer hyperpermeability:role of cAMP/PKA signaling. Arterioscler Thromb Vasc Biol 2008; 28:899-905.
37. 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.
38. Hattori Y, Suzuki M, Hattori S, Kasai K. Globular adiponectin upregulates nitric oxide production in vascular endothelial cells. Diabetologia.2003; 46:1543-1549.
39. Ouchi N, Kobayashi H, Kihara S, Kumada M, Sato K, Inoue T, et al. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem 2004; 279:1304-1309.
40. Ouedraogo R, et al. Adiponectin suppression of high-glucose-induced reactive oxygen species in vascular endothelial cells:evidence for involvement of a cAMP signaling pathway. Diabetes 2006; 55:1840-1846.
41. Ouchi N, Ohishi M, Kihara S, et al:Association of hypoadiponectinemia with impaired vasoreactivity. Hypertension 2003; 42:231-234.
42. Nishimura M, Izumiva Y, Hiquchi A, et al:Adiponectin prevents cerebral ischemic injury through endothelial nitric oxide synthase dependent mechanisms. Circulation 2008; 117:216-223.
43. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 2002; 106:2767-2770.
44. Okamoto Y, Folco EJ, Minami M, Wara AK, Feinberg MW, Sukhova GK, et al. Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Circ Res 2008; 102:218-225.
45. Fasshauer M, Kralisch S, Klier M, et al:Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2003; 301:1045-1050.
46. Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, et al. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 2004; 109:2046-2049.
47. Furukawa K, Hori M, Ouchi N, et al:Adiponectin down-regulates acylcoenzyme A:cholesterol acyltransferasea in cultured human monocyte-derived macrophages. Biochem biophys Res Commun 2004;317:831-836.
48. Takemura Y, Ouchi N, Shibata R, Aprahamian T, Kirber MT, Summer RS, et al. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest 2007; 117:375-386.
49. 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; 105:2893-2898.
50. Wang Y, Lam KS, XuJY, et al:Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerizationdependent manner. J Biol Chem 2005; 280:18341-18347.
51. 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.
52. 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.
53. Ouedraogo R, et al. Adiponectin deficiency increases leukocyte-endothelium interactions via upregulation of endothelial cell adhesion molecules in vivo. J Clin Invest 2007; 117:1718-1726.
54. 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.
55. Esposito K, Pontillo A, Di Palo C, et al:Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women; a randomized trial. JAMA 2003; 289:1799-1804.
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 Vasc Biol 2008; 28:1368-1374.
57. Kobashi C, Urakaze M, Kishida M, Kibayashi E, Kobayashi H, Kihara S, et al. Adiponectin inhibits endothelial synthesis of interleukin-8. Circ Res 2005; 97: 1245-1252.
58. Natarajan R, et al. Hypoxia inducible factor-1 upregulates adiponectin in diabetic mouse hearts and attenuates post-ischemic injury. J Cardiovasc Pharmacol 2008; 51:178-187.
59. Zhang H, Zhang C. Regulation of microvascular function by adipose tissue in obesity and type 2 diabetes:evidence of an adipose-vacular loop. Am J Biomed sci 2009; 1:133-142
60. Date H, et al. Adiponectin produced in coronary circulation regulates coronary flow reserve in nondiabetic patients with angiographically normal coronary arteries. Clin Cardiol 2006; 29:211-214.
61. Bora PS, et al. Expression of adiponectin in choroidal tissue and inhibition of laser induced choroidal neovascularization by adiponectin. FEBS Lett 2007; 58: 1977-1982.
62. Mahadev K, et al. Adiponectin inhibits vascular endothelial growth factor-induced migration of human coronary artery endothelial cells. Cardiovasc Res 2008; 78:376-384.
63. Braakenhielm E, et al. Adiponectin-induced antiangiogenesis and antitumor activity involve caspasemediated endothelial cell apoptosis. Proc Natl Acad Sci USA 2004; 101:2476-2481.
64. Frystyk J, et al. Increased serum adiponectin levels in type 1 diabetic patients with microvascular complications. Diabetologia 2005; 48:1911-1918.
65. Schalkwijk CG, et al. Adiponectin is inversely associated with renal function in Type 1 diabetic patients. J Clin Endocrinol Metab 2005; 91:129-135.
66. 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; 46:459-469.
67. Yatagai T, Nagasaka S, Taniguchi A, et al. Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 dia-betes mellitus. Metabolism 2003; 52:1274-1278.
68. 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.
69. 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; 73:534-539.
70. Vozarova B, Stefan N, Lindsay RS, et al. Low plasma adiponectin concentrations do not predict weight gain in humans. Diabetes 2002; 51:2964-2967.
71. Hulver MW, Zheng D, Tanner CJ, et al. Adiponectin is not altered with exercise training despite enhanced insulin action. Am J Physiol Endocrinol Metab 2002; 283:E861-E865.
72. Yatagai T, Nishida Y, Nagasaka S, et al. Relationship between exercise training-induced increase in insulin sensitivity and adiponectinemia in healthy men. Endocr J 2003; 50:233-238.
73. Valsamakis G, McTernan PQ Chetty R, et al. Modest weight loss and reduction in waist circumference after medical treatment are associated with favorable changes in serum adipocytokines. Metabolism 2004; 53:430-434.
74. Despres JP, Golay A, Sjostrom L. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med 2005; 353:2121-2134.
75. Calvani M, Scarfone A, Granato L, et al. Restoration of adiponectin pulsatility in severely obese subjects after weight loss. Diabetes 2004; 53:939-947.
76. Nakatani H, Hirose H, Yamamoto Y, et al. Significance of leptin and high-molecular weight adiponectin in the general population of Japanese male adolescents. Metabolism 2008; 57:157-162.
77. Kaser S, Tatarczyk T, Stadlmayr A, et al. Effect of obesity and insulin sensitivity on adiponectin isoform distribution. Eur J Clin Invest 2008; 38:827-34.
78. 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; 89:663.
79. Monzillo LU, Hamdy O, Horton ES:Effect of lifestyle modification on adipokine levels in obese subjects with insulin resistance. Obes Res 2003; 11:1048-1054.
80. 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;86:1930-1935.
81. 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.
82. 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.
83. Snehalatha C, Mukesh B, Simon M, et al. Plasma adiponectin is an independent predictor of type 2 diabetes in Asian Indians. Diabetes Care 2003; 26:3226-3229.
84. Stefan N, Vozarova B, Funahashi T, et al. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes 2002; 51:1884-1888.
85. Yamamoto Y, Hirose H, Saito I, et al. Adiponectin, an adipocyte-derived protein, predicts future insulin resistance:two-year follow-up study in Japanese population. J Clin Endocrinol Metab 2004; 89:87-90.
86. Duncan BB, Schmidt MI, Pankow JS, et al. Adiponectin and the development of type 2 diabetes:the atherosclerosis risk in communities study. Diabetes 2004; 53:2473-8.
87. 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;29:1357-1362
88. Nakashima R, Kamei N, Yamane K, et al. Decreased total and high molecular weight adiponectin are independent risk factors for the development of type 2 diabetes in Japanese-Americans. J Clin Endocrinol Metab 2006; 91:3873-3877.
89. Basu R, Pajvani UB, Rizza RA, et al. Selective downregulation of the high-molecular weight form of adiponectin in hyperinsulinemia and in type 2 diabetes. Differential regulation from nondiabetic subjects. Diabetes 2007; 56:2174-2177.
90. Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 2000; 20:1595-1599.
91. Tonelli J, Li W, Kishore P, et al. Mechanisms of early insulin-sensitizing effects of thiazolidinediones in type 2 diabetes. Diabetes 2004; 53:1621-1629.
92. Qurashi S, Mynarcik DC, McNurlan MA, et al. Importance of the high-molecular-mass isoform of adiponectin in improved insulin sensitivity with rosiglitazone treatment in HIV disease. Clin Sci (Lond) 2008; 115:197-202.
93. Yang WS, Lee WJ, Funahashi T, et al. Plasma adiponectin levels in overweight and obese Asians. Obes Res 2002; 10:1104-1110.
94. Matsubara M, Maruoka S, Katayose S. Decreased plasma adiponectin concentrations in women with dyslipidemia. J Clin Endocrinol Metab 2002; 87:2764-2769.
95. Huang KC, Lue BH, Yen RF, et al. Plasma adiponectin levels and metabolic factors in nondiabetic adolescents. Obes Res 2004; 12:119-124
96. Fruebis J, Tsao TS, Javorschi S, et al. Proteolytic cleavage product of 30-kda adipocyte complement-related proteinincreases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001; 98:2005-2010.
97. Schulze MB, Rimm EB, Shai Ⅰ, et al. Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes. Diabetes Care 2004; 27:1680-1687.
98. Kazumi T, Kawaguchi A, Hirano T, et al. Serum adiponectin is associated with high-density lipoprotein cholesterol, triglycerides, and low-density lipoprotein particle size in young healthy men. Metabolism 2004; 53:589-593.
99. Lara-Castro C, Luo N, Wallace P, et al. Adiponectin multimeric complexes and the metabolic syndrome trait cluster. Diabetes 2006; 55:249-259.
100. Lautamaki R, et al. Low serum adiponectin is associated with high circulating oxidized low-density lipoprotein in patients with type 2 diabetes mellitus and coronary artery disease. Metabolism 2007; 56:881-886.
101. Koh KK, Quon MJ, Han SH, et al. Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients. Circulation 2004; 110:3687-3692.
102. Bayes B, Granada ML, Lauzurica R, et al. Effect of low doses of atorvastatin on adiponectin, glucose homeostasis, and clinical inflammatory markers in kidney transplant recipients. Transplant Proc 2005; 37:3808-3812.
103. Gannage-Yared MH, Azar RR, Amm-Azar M, et al. Pravastatin does not affect insulin sensitivity and adipocytokines levels in healthy nondiabetic patients. Metabolism 2005;54:947-951.
104. Sonmez A, Dogru T, Tasci I, et al. The effect of fluvastatin on plasma adiponectin levels in dyslipidaemia. Clin Endocrinol (Oxf) 2006; 64:567-572.
105. Kazumi T, Kawaguchi A, Sakai K, et al. Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure. Diabetes Care 2002; 25:971-976.
106. Dzielinska Z, Januszewicz A, Wiecek A, et al. Decreased plasma concentration of a novel anti-inflammatory protein-adiponectin-in hypertensive men with coro-nary artery disease. Thromb Res 2003; 110:365-369.
107. Adamczak M, Wiecek A, Funahashi T, et al. Decreased plasma adiponectin concentration in patients with essential hypertension. Am J Hypertens 2003; 16:72-75.
108. Ohashi K, Kihara S, Ouchi N, et al. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension 2006; 47:1108-1116.
109. Shibata R, Ouchi N, Ito M, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med 2004; 10:1384-1389.
110. Chow WS, Cheung BM, Tso AW, et al. Hypoadiponectinemia as a predictor for the development of hypertension:a 5-year prospective study. Hypertension 2007; 49:1455-1461.
111. Koh KK, Quon MJ, Han SH, et al. Distinct vascular and metabolic effects of different classes of anti-hypertensive drugs. Int J Cardiol 2008 Dec 5. [Epub ahead of print]
112. Yilmaz MI, Sonmez A, Caglar K, et al. Effect of antihypertensive agents on plasma adiponectin levels in hypertensive patients with metabolic syndrome. Nephrology (Carlton) 2007; 12:147-153.
113. Wolk R, Berger P, Lennon RJ, Brilakis ES, Somers VK. Body mass index:a risk factor for unstable angina and myocardial infarction in patients with angiographically confirmed coronary artery disease. Circulation. 2003; 108:2206-2211
114. Orlander PR, Goff DC, Morrissey M, Ramsey DJ, Wear ML, Labarthe DR, Nichaman MZ. The relation of diabetes to the severity of acute myocardial infarction and post-myocardial infarction survival in Mexican-Americans and non-Hispanic whites. The Corpus Christi Heart Project. Diabetes.1994; 43:897-902.
115. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, Funahashi T, Ouchi N, Walsh K. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK-and COX-2-dependent mechanisms. Nat Med.2005; 11:1096-1103.
116. Pischon T, Girman CJ, Hotamisligil GS, et al:Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004; 291:1730-1737.
117. Schulze MB, Shai I, Rimm EB, et al:Adiponectin and future coronary heart disease events among men with type 2 diabetes. Diabetes 2005; 54:534-539.
118. Kojima S, Funahashi T, Otsuka F, Maruyoshi H, Yamashita T, Kajiwara I, et al. Future adverse cardiac events can be predicted by persistently low plasma adiponectin concentrations in men and marked reductions of adiponectin in women after acute myocardial infarction. Atherosclerosis 2002; 194:204-213.
119. 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; 90:5677-5683.
120. Nakamura Y, Shimada K, Fukuda D, et al:Implications of plasma concentrations of adiponectin in patients with coronary artery disease. Heart 2004; 90:528-533.
121. Wolk R, Berger P, Lennon RJ, et al:Association between plasma adiponectin levels and unstable coronary syndromes. Eur Heart J 2007; 28:292-298.
122. Zoccali C, Mallamaci F, Tripepi G:Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 2002; 13:134-141.
123. 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; 90:5677-83.
124. Soderberg S, Colquhoun D, Keech A, et al. Leptin, but not adiponectin, is a predictor of recurrent cardiovascular events in men:results from the lipid study. Int J Obes (Lond) 2009; 33:123-30.
125. Sattar N, Wannamethee Q Sarwar N, et al. Adiponectin and coronary heart disease:a prospective study and meta-analysis. Circulation 2006; 114:623-629.
126. Kistorp C, Faber J, Galatius S, et al. Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation 2005; 112:1756-1762.
127. Tamura T, Furukawa Y, Taniguchi R, et al. Serum adiponectin level as an independent predictor of mortality in patients with congestive heart failure. Circ J 2007;71:623-63 0.
128. Norrelund H, Wiggers H, Halbirk M, et al. Abnormalities of whole body protein turnover, muscle metabolism and levels of metabolic hormones in patients with chronic heart failure. J Intern Med 2006; 260:11-21.
129. McEntegart MB, Awede B, Petrie MC, et al. Increase in serum adiponectin concentration in patients with heart failure and cachexia:relationship with leptin, other cytokines, and b-type natriuretic peptide. Eur Heart J 2007; 28:829-35.
130. 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; 28:1723-30.
131. Anker SD, Rauchhaus M. Insights into the pathogenesis of chronic heart failure: Immune activation and cachexia. Curr Opin Cardiol 1999; 14:211-216.
132. Ingelsson E, Riserus U, Berne C, Frystyk J, Flyvbjerg A, Axelsson T, et al. Adiponectin and risk of congestive heart failure. JAMA 2006; 295:1772-1774.
133. Lin HV, Kim JY, Pocai A, Rossetti L, Shapiro L, Scherer PE, et al. Adiponectin resistance exacerbates insulin resistance in insulin receptor transgenic/knockout mice. Diabetes 2007; 56:1969-1976.
134. Mullen KL, Pritchard J, Ritchie I, Snook LA, Chabowski A, Bonen A, et al. Adiponectin resistance precedes the accumulation of skeletal muscle lipids and insulin resistance in high fat fed rats. Am J Physiol Regul Integr Comp Physiol 2008; 296:R243-R251.