Peroxisome proliferator-activated receptors (PPARs) in cardiovascular pathophysiology
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Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors which regulate the expression of target genes. Three types of PPAR have been identified: PPAR alpha, PPAR beta/delta and PPAR gamma. The known endogenous PPAR ligands are polyunsaturated fatty acids and eicosanoids, such as 15-deoxy-delta12,14-prostaglandin J2 and leukotriene B4. Two classes of drugs, fibrates and thiazolidinediones bind to PPAR alpha and PPAR gamma, respectively. PPARs are involved in the regulation of the lipid metabolism and adipogenesis but are also expressed in the vasculature. PPARs activators inhibit inflammatory reactions within the vascular wall, inhibit vascular smooth muscle cells migration and proliferation and affect foam cells formation by changing the expression different animal models of hypertension as well as in humans. PPAR gamma ligands inhibit the development of atherosclerosis in LDL receptor deficient and apolipoprotein E deficient mice and in diabetic humans. PPARgamma agonists have also been shown to attenuate myocardial hypertrophy and protect against ischemia-reperfusion injury.
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J. Beltowski, Katedra i Zaklad Patofizjologii AM, ul. Jaczewskiego 8, 20-090 Lublin, Poland