Published online before print July 21, 2003, doi: 10.1161/01.HYP.0000084370.74777.B6
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(Hypertension. 2003;42:664.)
© 2003 American Heart Association, Inc.
State of the Art Lectures |
Peroxisome Proliferator-Activated Receptors
Vascular and Cardiac Effects in Hypertension
From CIHR Multidisciplinary Research Group on Hypertension, Clinical Research Institute of Montreal, Montreal, Quebec, Canada.
Correspondence to Ernesto L. Schiffrin, MD, Clinical Research Institute of Montreal, 110 Pine Ave West, Montreal, Quebec, Canada H2W 1R7. E-mail ernesto.schiffrin{at}ircm.qc.ca
Peroxisome proliferator-activated receptors (PPAR) are nuclear receptors acting as transcription factors on numerous target genes after heterodimerization with the retinoid X receptor. PPAR-
and PPAR-
may be activated by different agonists, although the endogenous ligands are unknown. Although PPAR- is mainly involved in fatty acid oxidation and expressed in liver, kidney, and skeletal muscle, and PPAR- is mainly involved in fat cell differentiation and insulin sensitivity, both are expressed in smooth muscle cells and myocardium, although PPAR- are scarce in the latter. Activators of PPAR- such as fatty acids and fibrates, and PPAR- such as thiazolidinediones have been shown to exert antiproliferative effects, antagonize angiotensin II actions in vivo and in vitro, and exert antioxidant actions inhibiting generation of reactive oxygen species and activation of inflammatory mediators on blood vessels and the heart. These agents lowered blood pressure in several models of hypertension and corrected endothelial dysfunction. They exerted anti-inflammatory and antifibrotic actions on blood vessels and the heart. With the development of dual /-PPAR activators, these newer agents may become interesting therapeutic agents for prevention of vascular and cardiac complications of hypertension as well as for preventative therapy in other forms of cardiovascular disease.
Key Words: cardiovascular diseases • transcription • arteries • vasculature • remodeling • heart • fibrosis
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