Expression and function of PPARγ in rat and human vascular smooth muscle cells

被引:406
|
作者
Law, RE
Goetze, S
Xi, XP
Jackson, S
Kawano, Y
Demer, L
Fishbein, MC
Meehan, WP
Hsueh, WA
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Sch Med, Div Endocrinol Diabet & Hypertens, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Sch Med, Div Cardiol, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
关键词
atherosclerosis; restenosis; growth substances; migration; thiazolidinediones;
D O I
10.1161/01.CIR.101.11.1311
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is activated by fatty acids, eicosanoids, and insulin-sensitizing thiazolidinediones (TZDs). The TZD troglitazone (TRO) inhibits vascular smooth muscle cell (VSMC) proliferation and migration in vitro and in postinjury intimal hyperplasia. Methods and Results-Rat and human VSMCs express mRNA and nuclear receptors for PPAR gamma 1. Three PPAR gamma ligands, the TZDs TRO and rosiglitazone and the prostanoid 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), all inhibited VSMC proliferation and migration. PPAR gamma is upregulated in rat neointima at 7 days and 14 days after balloon injury and is also present in early human atheroma and precursor lesions. Conclusions-Pharmacological activation of PPAR gamma expressed in VSMCs inhibits their proliferation and migration, potentially limiting restenosis and atherosclerosis. These receptors are upregulated during vascular injury.
引用
收藏
页码:1311 / 1318
页数:8
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