Peroxisome proliferator-activated receptors and the cardiovascular system.
Insulin resistance syndrome (also called syndrome X) includes obesity, diabetes, hypertension, and dyslipidemia and is a complex phenotype of metabolic abnormalities. The disorder poses a major public health problem by predisposing individuals to coronary heart disease and stroke, the leading causes of mortality in Western countries. Given that hypertension, diabetes, dyslipidemia, and obesity exhibit a substantial heritable component, it is postulated that certain genes may predispose some individuals to this cluster of cardiovascular risk factors. Emerging data suggest that peroxisome proliferator-activated receptors (PPARs), including alpha, gamma, and delta, are important determinants that may provide a functional link between obesity, hypertension, and diabetes. It has been well documented that hypolipidemic fibrates and antidiabetic thiazolidinediones are synthetic ligands for PPAR alpha and PPAR gamma, respectively. In addition, PPAR natural ligands, such as leukotriene B4 for PPAR alpha, 15-deoxy-delta 12,14-prostaglandin J2 for PPAR gamma, and prostacyclin for PPAR delta, are known to be eicosanoids and fatty acids. Studies have documented that PPARs are present in all critical vascular cells: endothelial cells, vascular smooth muscle cells, and monocyte-macrophages. These observations suggest that PPARs not only control lipid metabolism but also regulate vascular diseases such as atherosclerosis and hypertension. In this review, we present structure and tissue distribution of PPAR nuclear receptors, discuss the mechanisms of action and regulation, and summarize the rapid progress made in this area of study and its impact on the cardiovascular system.
Chen
Yuqing E
YE
Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia 30310, USA.
Fu
Mingui
M
Zhang
Jifeng
J
Zhu
Xiaojun
X
Lin
Yiming
Y
Akinbami
Mukaila A
MA
Song
Qing
Q
D000818:Animals; D001161:Arteriosclerosis; D001808:Blood Vessels; D002318:Cardiovascular Diseases / Q000235:genetics; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System; D005786:Gene Expression Regulation; D014644:Genetic Variation; D006801:Humans; D006973:Hypertension; D009928:Organ Specificity; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000032:analysis / Q000737:chemistry / Q000235:genetics / Q000502:physiology
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors