PGC-1α Inhibits Oleic Acid Induced Proliferation and Migration of Rat Vascular Smooth Muscle Cells

BACKGROUND: Oleic acid (OA) stimulates vascular smooth muscle cell (VSMC) proliferation and migration. The precise mechanism is still unclear. We sought to investigate the effects of peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 alpha (PGC-1α) on OA-induced VSMC proliferation and migration. PRINCIPAL FINDINGS: Oleate and palmitate, the most abundant monounsaturated fatty acid and saturated fatty acid in plasma, respectively, differently affect the mRNA and protein levels of PGC-1α in VSMCs. OA treatment resulted in a reduction of PGC-1α expression, which may be responsible for the increase in VSMC proliferation and migration caused by this fatty acid. In fact, overexpression of PGC-1α prevented OA-induced VSMC proliferation and migration while suppression of PGC-1α by siRNA enhanced the effects of OA. In contrast, palmitic acid (PA) treatment led to opposite effects. This saturated fatty acid induced PGC-1α expression and prevented OA-induced VSMC proliferation and migration. Mechanistic study demonstrated that the effects of PGC-1α on VSMC proliferation and migration result from its capacity to prevent ERK phosphorylation. CONCLUSIONS: OA and PA regulate PGC-1α expression in VSMCs differentially. OA stimulates VSMC proliferation and migration via suppression of PGC-1α expression while PA reverses the effects of OA by inducing PGC-1α expression. Upregulation of PGC-1α in VSMCs provides a potential novel strategy in preventing atherosclerosis.