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(Hypertension. 2004;43:297.)
© 2004 American Heart Association, Inc.

Corcoran Lecture

Peroxisome Proliferator-Activated Receptor : Implications for Cardiovascular Disease

From Division of Endocrinology, Diabetes, and Hypertension, David Geffen School of Medicine, University of California, Los Angeles.

Correspondence to Willa A. Hsueh, Division of Endocrinology, Diabetes, and Hypertension, David Geffen School of Medicine, University of California, Los Angeles Warren Hall, Suite 24–130, 900 Veteran Avenue, Los Angeles, CA 90095. E-mail whsueh{at}mednet.ucla.edu

Abstract

Peroxisome proliferator-activated receptor (PPAR) is a ligand-activated transcription factor belonging to the nuclear hormone receptor superfamily. PPAR is expressed by macrophages, endothelial cells, and vascular smooth muscle cells. It regulates gene expression of key proteins involved in lipid metabolism, vascular inflammation, and proliferation contributing to atherogenesis and postangioplasty restenosis. The discovery of synthetic ligands for PPAR has led to significant enhancement of our understanding of the mechanism of their ligand-dependent activation and subsequent biological effects, particularly with respect to the role of PPAR in vascular pathophysiology. The thiazolidinedione PPAR agonists not only improve insulin resistance in patients with type II diabetes but also exert a broad spectrum of antiatherogenic effects in vitro and in animal models of atherosclerosis. In this review, we summarize the important role of PPAR as a molecular target for thiazolidinediones and its implications for the control of vascular inflammation and proliferation for the cardiovascular system.

Key Words: atherosclerosis • diabetes mellitus • peroxisome proliferator-activated receptor • angiotensin • inflammation

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