PPARs and the cardiovascular system.

Abstract

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear hormone-receptor superfamily. Originally cloned in 1990, PPARs were found to be mediators of pharmacologic agents that induce hepatocyte peroxisome proliferation. PPARs also are expressed in cells of the cardiovascular system. PPAR gamma appears to be highly expressed during atherosclerotic lesion formation, suggesting that increased PPAR gamma expression may be a vascular compensatory response. Also, ligand-activated PPAR gamma decreases the inflammatory response in cardiovascular cells, particularly in endothelial cells. PPAR alpha, similar to PPAR gamma, also has pleiotropic effects in the cardiovascular system, including antiinflammatory and antiatherosclerotic properties. PPAR alpha activation inhibits vascular smooth muscle proinflammatory responses, attenuating the development of atherosclerosis. However, PPAR delta overexpression may lead to elevated macrophage inflammation and atherosclerosis. Conversely, PPAR delta ligands are shown to attenuate the pathogenesis of atherosclerosis by improving endothelial cell proliferation and survival while decreasing endothelial cell inflammation and vascular smooth muscle cell proliferation. Furthermore, the administration of PPAR ligands in the form of TZDs and fibrates has been disappointing in terms of markedly reducing cardiovascular events in the clinical setting. Therefore, a better understanding of PPAR-dependent and -independent signaling will provide the foundation for future research on the role of PPARs in human cardiovascular biology.

• Authors: Milton Hamblin, Lin Chang, Yanbo Fan, Jifeng Zhang, Y Eugene Chen
• Journal: Antioxidants & redox signaling (Antioxid Redox Signal) Vol. 11 Issue 6 Pg. 1415-52 (Jun 2009) ISSN: 1557-7716 [Electronic] United States
• PMID: 19061437 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• PPAR alpha
• PPAR delta
• PPAR gamma
• Peroxisome Proliferator-Activated Receptors

Topics

• Animals
• Cardiovascular System (metabolism)
• Endothelial Cells (cytology, metabolism)
• Humans
• Models, Biological
• Muscle, Smooth, Vascular (cytology)
• PPAR alpha (metabolism)
• PPAR delta (metabolism)
• PPAR gamma (metabolism)
• Peroxisome Proliferator-Activated Receptors (metabolism)