Peroxisome Proliferator-Activated Receptor α Plays 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 PPARα 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 PPARα knockout and wild type (WT) mice, treated and untreated with Wy14643, a PPARα activator. Up-regulated MCP-1 and TF expression and more neointimal formation were observed in the PPARα(-/-) mice compared with WT mice. The activation of PPARα 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 PPARα resulting in decreased leukocyte infiltration and TF expression.