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8TH INTERNATIONAL SYMPOSIUM ON RESISTANCE ARTERIES
New Developments in Resistance Artery Research: From Molecular Biology to Bedside

Peroxisome proliferator-activated receptors and cardiovascular remodeling

Canadian Institute of Health Research Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, Canada

Submitted 27 July 2004 ; accepted in final form 28 September 2004

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that heterodimerize with the retinoid X receptor and then modulate the function of many target genes. Three PPARs are known: , /, and . The better known are PPAR- and PPAR-, which may be activated by different synthetic agonists, although the endogenous ligands are unknown. PPAR- is involved in fatty acid oxidation and expressed in the liver, kidney, and skeletal muscle, whereas PPAR- is involved in fat cell differentiation, lipid storage, and insulin sensitivity. However, both have been shown to be present in variable amounts in cardiovascular tissues, including endothelium, smooth muscle cells, macrophages, and the heart. The activators of PPAR- (fibrates) and PPAR- (thiazolidinediones or glitazones) antagonized the actions of angiotensin II in vivo and in vitro and exerted 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 prevention of cardiovascular disease.

arteries; endothelium; heart; inflammation

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