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PPAR Activity in the Vessel Wall: Anti-Atherogenic Properties

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The nuclear receptor peroxisome proliferator-activated receptor γ(PPARγ) is a ligand-dependent transcription factor that controls the expression of specific target genes involved in adipogenesis, inflammatory responses, and lipid metabolism. Atherosclerotic plaque progression is influenced by intraplaque inflammation and extracellular matrix deposition. Anti-inflammatory, anti-proliferative and antiprotease activity of PPARγ may modulate the atherosclerotic process. PPARγ is expressed in atherosclerotic lesions of human coronary arteries and has direct anti-inflammatory effects in the vascular wall. Thiazolidinediones (TZD) are ligands for PPARγ used therapeutically to enhance insulin-mediated glucose uptake in persons with type 2 diabetes. These agents may also exert anti-atherogenic effects on cells of the vessel wall including macrophages, vascular endothelium and vascular smooth muscle. This review discusses the impact of PPARγ and its activators in the numerous processes involved in the formation of atherosclerotic lesions. We provide an overview of in vitro and in vivo data in cell lines, animal models, and humans demonstrating the ways in which PPARγ activation alters the biology of the arterial wall.
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Keywords: 15d-PGJ2; 27-hydroxylase; ABCA1; LXR; atheroma; oxysterol; pioglitazone; rosiglitazone

Document Type: Research Article

Affiliations: Vascular Biology Institute, Winthrop-University Hospital, 222 Station Plaza, North, Suite 511-A, Mineola, NY 11501, USA.

Publication date: 2006-11-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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