PPARβ/δ Agonists Modulate Platelet Function via a Mechanism Involving PPAR Receptors and Specific Association/Repression of PKCα-Brief Report

被引：38

作者：

Ali, Ferhana Y. ^{[1
,2
]}

Hall, Matthew G. ^{[3
]}

Desvergne, Beatrice ^{[3
]}

Warner, Timothy D. ^{[2
]}

Mitchell, Jane A. ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England

[2] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England

[3] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2009年 / 29卷 / 11期

关键词：

platelets; PPAR beta/delta; PKC alpha; knockout mice; PROTEIN-KINASE-C; FIBROBLASTS;

D O I：

10.1161/ATVBAHA.109.193367

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives-Peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) is a nuclear receptor found in platelets. PPAR beta/delta agonists acutely inhibit platelet function within a few minutes of addition. As platelets are anucleated, the effects of PPAR beta/delta agonists on platelets must be nongenomic. Currently, the particular role of PPAR beta/delta receptors and their intracellular signaling pathways in platelets are not known. Methods and Results-We have used mice lacking PPAR beta/delta (PPAR beta/delta(-/-)) to show the effects of the PPAR beta/delta agonist GW501516 on platelet adhesion and cAMP levels are mediated specifically by PPAR beta/delta, however GW501516 had no PPAR beta/delta-specific effect on platelet aggregation. Studies in human platelets showed that PKC alpha, which can mediate platelet activation, was bound and repressed by PPAR beta/delta after platelets were treated with GW501516. Conclusions-These data provide evidence of a novel mechanism by which PPAR receptors influence platelet activity and thereby thrombotic risk. (Arterioscler Thromb Vasc Biol. 2009; 29: 1871-1873.)

引用

页码：1871 / 1873

页数：3

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