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(Circulation Research. 2008;102:283.)
© 2008 American Heart Association, Inc.

Review

Peroxisome Proliferator-Activated Receptor-–Mediated Effects in the Vasculature

Sheng Zhong Duan, Michael G. Usher, Richard M. Mortensen

From the Departments of Molecular and Integrative Physiology (S.Z.D., M.G.U., R.M.M.), Pharmacology (R.M.M.), and Internal Medicine (R.M.M.), Metabolism Endocrinology and Diabetes Division, University of Michigan Medical School, Ann Arbor.

Correspondence to Richard M. Mortensen, Department of Molecular and Integrative Physiology, University of Michigan Medical School, 7726 Med Sci II, 1150 W Med Ctr Dr, Ann Arbor, MI 48109-0622. E-mail rmort{at}umich.edu

This Review is part of a thematic series on Adipocyte Signaling in the Cardiovascular System, which includes the following articles:

Adipose Tissue, Inflammation, and Cardiovascular Disease

Adipocyte Signaling and Lipid Homeostasis: Sequelae of Insulin-Resistant Adipose Tissue

Diabetic Cardiomyopathy: The Search for a Unifying Hypothesis

Adiposity and Cardiovascular Disorders: Disturbance of the Regulatory System Consisting of Humoral and Neuronal Signals

Peroxisome Proliferator-Activated Receptor-–Mediated Effects in the Vasculature
Philipp Scherer Guest Editor

Peroxisome proliferator-activated receptor (PPAR)- is a nuclear receptor and transcription factor in the steroid superfamily. PPAR- agonists, the thiazolidinediones, are clinically used to treat type 2 diabetes. In addition to its function in adipogenesis and increasing insulin sensitivity, PPAR- also plays critical roles in the vasculature. In vascular endothelial cells, PPAR- activation inhibits endothelial inflammation by suppressing inflammatory gene expression and therefore improves endothelial dysfunction. In vascular smooth muscle cells, PPAR- activation inhibits proliferation and migration and promotes apoptosis. In macrophages, PPAR- activation suppresses inflammation by regulating gene expression and increases cholesterol uptake and efflux. A recurring theme in many cell types is the modulation of the innate immunity system particularly through altering the activity of the nuclear factor B. This system is likely to be even more prominent in modulating disease in vascular cells. The effects of PPAR- in the vascular cells translate into the beneficial function of this transcription factor in vascular disorders, including hypertension and atherosclerosis. Both human genetic studies and animal studies using transgenic mice have demonstrated the importance of PPAR- in these disorders. However, recent clinical studies have raised significant concerns about the cardiovascular side effects of thiazolidinediones, particularly rosiglitazone. Weighing the potential benefit and harm of PPAR- activation and exploring the functional mechanisms may provide a balanced view on the clinical use of these compounds and new approaches to the future therapeutics of vascular disorders associated with diabetes.

Key Words: PPAR-, vascular endothelial cells • vascular smooth muscle cells • macrophages • vascular disorders