PPAR-γ as a therapeutic target in cardiovascular disease: evidence and uncertainty

被引：66

作者：

Huang, Janice V.

Greyson, Clifford R.

Schwartz, Gregory G. ^{[1
]}

机构：

[1] US Dept Vet Affairs, Denver VA Med Ctr, Cardiol Sect, Denver, CO USA

来源：

JOURNAL OF LIPID RESEARCH | 2012年 / 53卷 / 09期

基金：

美国国家卫生研究院;

关键词：

peroxisome proliferator-activated receptor gamma; diabetes; insulin resistance; fatty acids; atherosclerosis; randomized clinical trials; ACTIVATED-RECEPTOR-GAMMA; TYPE-2; DIABETES-MELLITUS; DENSITY-LIPOPROTEIN-CHOLESTEROL; ENDOTHELIAL PROGENITOR CELLS; IMPAIRED GLUCOSE-TOLERANCE; INTIMA-MEDIA THICKNESS; K-ATP CHANNEL; ALL-CAUSE MORTALITY; FREE FATTY-ACIDS; ISCHEMIC VENTRICULAR-FIBRILLATION;

D O I：

10.1194/jlr.R024505

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a key regulator of fatty acid metabolism, promoting its storage in adipose tissue and reducing circulating concentrations of free fatty acids. Activation of PPAR-gamma has favorable effects on measures of adipocyte function, insulin sensitivity, lipoprotein metabolism, and vascular structure and function. Despite these effects, clinical trials of thiazolidinedione PPAR-gamma activators have not provided conclusive evidence that they reduce cardiovascular morbidity and mortality. The apparent disparity between effects on laboratory measurements and clinical outcomes may be related to limitations of clinical trials, adverse effects of PPAR-gamma activation, or off-target effects of thiazolidinedione agents.(jlr) This review addresses these issues from a clinician's perspective and highlights several ongoing clinical trials that may help to clarify the therapeutic role of PPAR-gamma activators in cardiovascular disease.-Huang, J. V., C. R. Greyson, and G. G. Schwartz. PPAR-gamma as a therapeutic target in cardiovascular disease: evidence and uncertainty. J. Lipid Res. 2012. 53: 1738-1754.

引用

页码：1738 / 1754

页数：17

共 217 条

[1]

Comparison of three treatment approaches to decreasing cardiovascular disease risk in nondiabetic insulin-resistant dyslipidemic subjects [J].

Abbasi, Fahim ;

Chen, Yii-Der Ida ;

Farin, Helke M. F. ;

Lamendola, Cindy ;

Reaven, Gerald M. .

AMERICAN JOURNAL OF CARDIOLOGY, 2008, 102 (01) :64-69

[2]

Relationship between changes in insulin sensitivity and associated cardiovascular disease risk factors in thiazolidinedione-treated, insulin-resistant, nondiabetic individuals: pioglitazone versus rosiglitazone [J].

Abbasi, Fahim ;

Lima, Nereida K. C. ;

Reaven, Gerald M. .

METABOLISM-CLINICAL AND EXPERIMENTAL, 2009, 58 (03) :373-378

[3]

Discovery of (2R)-2-(3-{3-[(4-Methoxyphenyl)carbonyl]-2-methyl-6-(trifluoromethoxy)-1H-indol-1-yl}phenoxy)butanoic Acid (MK-0533): A Novel Selective Peroxisome Proliferator-Activated Receptor γ Modulator for the Treatment of Type 2 Diabetes Mellitus with a Reduced Potential to Increase Plasma and Extracellular Fluid Volume [J].

Acton, John J., III ;

Akiyama, Taro E. ;

Chang, Ching H. ;

Colwell, Lawrence ;

Debenham, Sheryl ;

Doebber, Thomas ;

Einstein, Monica ;

Liu, Kun ;

McCann, Margaret E. ;

Moller, David E. ;

Muise, Eric S. ;

Tan, Yugen ;

Thompson, John R. ;

Wong, Kenny K. ;

Wu, Margaret ;

Xu, Libo ;

Meinke, Peter T. ;

Berger, Joel P. ;

Wood, Harold B. .

JOURNAL OF MEDICINAL CHEMISTRY, 2009, 52 (13) :3846-3854

[4]

Activators of peroxisome proliferator-activated receptor γ have depot-specific effects on human preadipocyte differentiation [J].

Adams, M ;

Montague, CT ;

Prins, JB ;

Holder, JC ;

Smith, SA ;

Sanders, L ;

Digby, JE ;

Sewter, CP ;

Lazar, MA ;

Chatterjee, VKK ;

O'Rahilly, S .

JOURNAL OF CLINICAL INVESTIGATION, 1997, 100 (12) :3149-3153

[5]

Acute coronary syndromes and diabetes: is intensive lipid lowering beneficial? Results of the PROVE IT-TIMI 22 trial [J].

Ahmed, Shaheeda ;

Cannon, Christopher P. ;

Murphy, Sabina A. ;

Braunwald, Eugene .

EUROPEAN HEART JOURNAL, 2006, 27 (19) :2323-2329

[6]

Selective activation of PPARγ in skeletal muscle induces endogenous production of adiponectin and protects mice from diet-induced insulin resistance [J].

Amin, Rajesh H. ;

Mathews, Suresh T. ;

Camp, Heidi S. ;

Ding, Liyun ;

Leff, Todd .

AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2010, 298 (01) :E28-E37

[7]

Lack of the serum and glucocorticoid-inducible kinase SGK1 attenuates the volume retention after treatment with the PPARγ agonist pioglitazone [J].

Artunc, Ferruh ;

Sandulache, Diana ;

Nasir, Omaima ;

Boini, Krishna M. ;

Friedrich, Bjoern ;

Beier, Norbert ;

Dicks, Edith ;

Poetzsch, Sven ;

Klingel, Karin ;

Amann, Kerstin ;

Blazer-Yost, Bonnie L. ;

Scholz, Wolfgang ;

Risler, Teut ;

Kuhl, Dietmar ;

Lang, Florian .

PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2008, 456 (02) :425-436

[8]

Conditional knockout of macrophage PPARγ increases atherosclerosis in C57BL/6 and low-density lipoprotein receptor-deficient mice [J].

Babaev, VR ;

Yancey, PG ;

Ryzhov, SV ;

Kon, V ;

Breyer, MD ;

Magnuson, MA ;

Fazio, S ;

Linton, MF .

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2005, 25 (08) :1647-1653

[9]

Effects of Pioglitazone on Intramyocellular Fat Metabolism in Patients with Type 2 Diabetes Mellitus [J].

Bajaj, Mandeep ;

Baig, Rais ;

Suraamornkul, Swangjit ;

Hardies, Lou Jean ;

Coletta, Dawn K. ;

Cline, Gary W. ;

Monroy, Adriana ;

Koul, Shailja ;

Sriwijitkamol, Apiradee ;

Musi, Nicolas ;

Shulman, Gerald I. ;

DeFronzo, Ralph A. .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2010, 95 (04) :1916-1923

[10]

PPAR dual agonists: Are they opening Pandora's box? [J].

Balakumar, Pitchal ;

Rose, Madhankumar ;

Ganti, Subrahmanya S. ;

Krishan, Pawan ;

Singh, Manjeet .

PHARMACOLOGICAL RESEARCH, 2007, 56 (02) :91-98

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