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* To whom correspondence should be addressed. E-mail: ernesto.schiffrin{at}ircm.qc.ca.
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that heterodimerize with the retinoid X receptor (RXR) and then modulate the function of many target genes. Three PPARs are known, 
, 
/
and 
. The better known are PPAR and PPAR that may be activated by different synthetic agonists, although the endogenous ligands are unknown. PPAR is involved in fatty acid oxidation and expressed in liver, kidney and skeletal muscle, whereas PPAR is involved in fat cell differentiation and insulin sensitivity, the latter through action on skeletal muscle. However, both have been shown to be present in variable amounts in cardiovascular tissues, including the endothelium, smooth muscle cells and the heart. The activators of PPAR (fibrates), and PPAR (thiazolidinediones) antagonize the actions of angiotensin II in vivo and in vitro, and exert cardiovascular antioxidant and anti-inflammatory effects. PPAR activators lowered blood pressure, induced favorable effects on the heart, and corrected vascular structure and endothelial dysfunction in several rodent models of hypertension. Activators of PPARs may become therapeutic agents useful in the prevention of cardiovascular disease beyond their effects on carbohydrate and lipid metabolism. Some side effects such as weight gain as well as documented aggravation of advanced heart failure through fluid retention by glitazones may however limit their therapeutic application in cardiovascular prevention.
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