Expression and Function of PPARγ in Rat and Human Vascular Smooth Muscle Cells

作者：Ronald E. Law, Stephan Goetze, Xiao-Ping Xi, Simon M. Jackson, Yasuko Kawano, Linda L. Demer, Michael C. Fishbein, Woerner P. Meehan, Willa A. Hsueh · 发表于：Circulation · 年份：2000 · DOI：10.1161/01.cir.101.11.1311 · 被引用次数：446 · 研究领域：Peroxisome Proliferator-Activated Receptors、Diabetes, Cardiovascular Risks, and Lipoproteins、Cardiovascular Function and Risk Factors

BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPARgamma) 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 PPARgamma1. Three PPARgamma ligands, the TZDs TRO and rosiglitazone and the prostanoid 15-deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2), all inhibited VSMC proliferation and migration. PPARgamma 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 PPARgamma expressed in VSMCs inhibits their proliferation and migration, potentially limiting restenosis and atherosclerosis. These receptors are upregulated during vascular injury.