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(Hypertension. 2005;46:267.)
© 2005 American Heart Association, Inc.

Editorial Commentaries

More Evidence of Cardiorenal Protective Effects of Peroxisome Proliferator-Activated Receptor Activation

From the CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, University of Montreal, Quebec, Canada.

Correspondence to Ernesto L. Schiffrin, MD, PhD, FRCPC, Clinical Research Institute of Montreal, 110 Pine Ave W, Montreal, Quebec, Canada H2W 1R7. E-mail ernesto.schiffrin@ircm.qc.ca

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that heterodimerize with the retinoid X receptor and modulate functions of many target genes. Three PPARs, , ß/, and , have been demonstrated. PPAR is involved in fatty acid oxidation and expressed in liver, kidney, and skeletal muscle; PPARß/ is ubiquitous and regulates lipid metabolism; and PPAR plays a role in fat cell differentiation, lipid storage, and insulin sensitivity.¹ PPARs are present in cardiovascular tissues, including the endothelium, smooth muscle cells, macrophages, and the heart.^2–4 Fibrates (hypolipemic agents) and fatty acids activate PPAR, and thiazolidinediones or glitazones (antidiabetic drugs) stimulate PPAR.⁵ However, the endogenous ligands of PPARs remain unknown.

PPAR and PPAR have increasingly been demonstrated to exert cardiovascular protective effects, independent of their metabolic actions.^3,4 Whereas metabolic effects of PPARs are mediated by activation of a PPAR-responsive element present in the promoter region of different genes, the cardiovascular protective actions may result from anti-inflammatory and antioxidant actions mediated by transrepression of proinflammatory and pro-oxidant genes. PPAR activators lowered blood pressure, induced favorable effects on the heart, and corrected vascular structure and endothelial dysfunction in several rodent models of hypertension, including genetic models,⁶ angiotensin II,^7–9 and endothelin-1 (ET-1)–dependent hypertension.¹⁰ These effects were associated with antioxidant, anti-inflammatory, antiproliferative, antihypertrophic, and antifibrotic effects.¹¹ Different studies have demonstrated as well that activation of PPAR exerts antiatherosclerotic actions.¹² PPAR, through its effect to lower triglycerides as well as its anti-inflammatory action, also prevents progression of atherosclerosis.¹³ We^3,4 and others have proposed that activators . . . [Full Text of this Article]