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Hypertension. 2005;46:1086-1092
Published online before print October 17, 2005, doi: 10.1161/01.HYP.0000187900.36455.4c
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(Hypertension. 2005;46:1086.)
© 2005 American Heart Association, Inc.


Brief Reviews

Beneficial Vascular and Metabolic Effects of Peroxisome Proliferator-Activated Receptor-{alpha} Activators

Seung Hwan Han; Michael J. Quon; Kwang Kon Koh

From the Division of Cardiology (S.H.H., K.K.K.), Gil Heart Center, Gachon Medical School, Incheon, Korea, and the Diabetes Unit (M.J.Q.), Laboratory of Clinical Investigation, NCCAM, NIH, Bethesda, Md.

Correspondence to Kwang Kon Koh, MD, PhD, Division of Cardiology, Gil Heart Center, Gachon Medical School, 1198 Kuwol-dong, Namdong-gu, Incheon, South Korea 405-760. E-mail kwangk{at}ghil.com

Fibric acid is a synthetic ligand of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-{alpha} that is highly expressed in skeletal muscle and heart, where it promotes ß-oxidation of fatty acids to mediate hypolipidemic actions. PPAR-{alpha} regulates expression of key proteins involved in atherogenesis, vascular inflammation, plaque instability, and thrombosis. Thus, PPAR-{alpha} may exert direct antiatherogenic actions in the vascular wall. Endothelial dysfunction associated with the metabolic syndrome and other insulin-resistant states is characterized by impaired insulin-stimulated nitric oxide production from the endothelium and decreased blood flow to skeletal muscle. Thus, improvement in insulin sensitivity leads to improved endothelial function. This may be an additional mechanism whereby fibrates decrease the incidence of coronary heart disease. Adiponectin is a protein secreted specifically by adipose cells that may couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. In this review, we discuss the mechanisms underlying the vascular and metabolic effects of fibrates that may act synergistically to prevent or regress atherosclerosis and coronary heart disease.


Key Words: fibrates • endothelium • adipose tissue • insulin resistance • cardiovascular diseases




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