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(Circulation Research. 2009;104:4.)
© 2009 American Heart Association, Inc.

Editorials

Suppression of Peroxisome Proliferator-Activated Receptor- Activity by Angiotensin II in Vascular Smooth Muscle Involves Bcr Kinase

The Fire That Drowns The Water

Ernesto L. Schiffrin, Pierre Paradis

From the Lady Davis Institute for Medical Research (E.L.S., P.P.) and Department of Medicine (E.L.S.), Sir Mortimer B. Davis–Jewish General Hospital, McGill University, Montreal, Quebec, Canada.

Correspondence to Ernesto L. Schiffrin MD, PhD, FRSC, FRCPC, Department of Medicine, SMBD-Jewish General Hospital, #B-127, 3755 Côte-Ste-Catherine Rd, Montreal, Quebec, Canada H3T 1E2. E-mail ernesto.schiffrin@mcgill.ca

See related article, pages 69–78

Key Words: nuclear receptor • PDGF • inflammation • remodeling hypertension

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Peroxisome proliferator activator receptors (PPARs) are nuclear receptors that exert effects on lipid and carbohydrate metabolism. Three members of the PPAR family have been identified: , β/, and . PPAR- and PPAR-β/ regulate genes that play a role in lipid metabolism and fatty acid oxidation. PPAR- is expressed mostly in adipose tissue, controls adipocyte differentiation and lipid storage, and sensitizes tissues to the action of insulin. PPAR- is also abundantly expressed in the arterial tree. Natural ligands of PPAR- include free fatty acids and prostaglandin D₂ derivatives such as 15-deoxy-^{12, 14}-prostaglandin J₂ (15d-PGJ₂). Synthetic ligands for PPAR- include the thiazolidinediones (glitazones), which are insulin sensitizers used for treatment of diabetes mellitus. Activation of PPAR- with thiazolidinediones has been shown to result in abrogation of effects of angiotensin (Ang) II in rats. PPAR- ligands (rosiglitazone and pioglitazone) prevented development of hypertension in Ang II–infused rats, regressed vascular remodeling, reduced vascular inflammation, and improved endothelial function.¹ Vascular DNA synthesis, nuclear factor (NF)-B activity and expression of cell cycle proteins, Ang II type 1 receptors, vascular cell adhesion molecule (VCAM)-1, and platelet and endothelial cell adhesion molecule (PECAM), which were increased by Ang II infusion, were blunted by pioglitazone or rosiglitazone. This suggested that PPAR- could act as an endogenous Ang II antagonist, modulating the effects of the renin–angiotensin–aldosterone system. Similar effects were found in a mineralocorticoid hypertensive model, the deoxycorticosterone (DOCA)-salt rat, which is associated with activation of the endothelin system and in which the effects of PPAR- ligands . . . [Full Text of this Article]

Related Article:

Bcr Kinase Activation by Angiotensin II Inhibits Peroxisome Proliferator-Activated Receptor Transcriptional Activity in Vascular Smooth Muscle Cells

Jeffrey D. Alexis, Nadan Wang, Wenyi Che, Nicole Lerner-Marmarosh, Abha Sahni, Vyacheslav A. Korshunov, Yiping Zou, Bo Ding, Chen Yan, Bradford C. Berk, and Jun-ichi Abe
Circ. Res. 2009 104: 69-78. [Abstract] [Full Text] [PDF]