Peroxisome Proliferator-Activated ReceptorαPlays an Important Role in the Expression of Monocyte Chemoattractant Protein-1 and Neointimal Hyperplasia after Vascular Injury

Peroxisome proliferator-activated receptor α is a member of the nuclear receptor superfamily. It modulates smooth muscle cell proliferation and inflammatory cytokines in vitro. In this study, we tested the hypothesis that PPAR α would decrease the expression of monocyte chemoattractant protein-1 and tissue factor, and inhibit neointimal formation in a murine double carotid artery injury model. Carotid artery injury was performed in the PPAR α knockout and wild type (WT) mice, treated and untreated with Wy14643, a PPAR α activator. Up-regulated MCP-1 and TF expression and more neointimal formation were observed in the PPAR α −/− mice compared with WT mice. The activation of PPAR α resulted in further decreased neointimal formation. Our data further suggest that the decrease in neointimal formation is due to down-regulation of MCP-1 by PPAR α resulting in decreased leukocyte infiltration and TF expression.