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

• DOI: 10.1161/01.cir.101.11.1311
• Publication Date: 2012-06-12T00:42:29Z
• Authors: Ronald E. Law; Stephan Goetze; Xiao-Ping Xi; Simon Jackson; Yasuko Kawano; Linda Demer; Michael C. Fishbein; Woerner P. Meehan; Willa A. Hsueh
• Keywords: Platelet-Derived Growth Factor; Receptors, Cytoplasmic and Nuclear; 3T3 Cells; Coronary Artery Disease; DNA; Ligands; Muscle, Smooth, Vascular; Catheterization; Rats; Mice; 03 medical and health sciences; 0302 clinical medicine; Cell Movement; Animals; Humans; Fibroblast Growth Factor 2; RNA, Messenger; Tunica Intima; Aorta; Cell Division; Subcellular Fractions; Transcription Factors

Background —Peroxisome proliferator–activated receptor-γ (PPARγ) 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 PPARγ1. Three PPARγ ligands, the TZDs TRO and rosiglitazone and the prostanoid 15-deoxy-Δ 12,14 -prostaglandin J2 (15d-PGJ2), all inhibited VSMC proliferation and migration. PPARγ 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 PPARγ expressed in VSMCs inhibits their proliferation and migration, potentially limiting restenosis and atherosclerosis. These receptors are upregulated during vascular injury.