TI - PGC-1alpha Is a Key Regulator of Glucose-Induced Proliferation and Migration in Vascular Smooth Muscle Cells New Finding of PGC-1alpha's Role . AB - Background Atherosclerosis is a complex pathological condition caused by a number of mechanisms including the accelerated proliferation of vascular smooth muscle cells ( VSMCs ) . Diabetes is likely to be an important risk factor for atherosclerosis , as hyperglycemia induces vascular smooth muscle cell ( VSMC ) proliferation and migration and may thus contribute to the formation of atherosclerotic lesions . This study was performed to investigate whether PGC-1alpha , a PPARgamma coactivator and metabolic master regulator , plays a role in regulating VSMC proliferation and migration induced by high glucose . Methodology/Principal Findings PGC-1alpha mRNA levels are decreased in blood vessel media of STZ-treated diabetic rats . In cultured rat VSMCs , high glucose dose-dependently inhibits PGC-1alpha mRNA expression . Overexpression of PGC-1alpha either by infection with adenovirus , or by stimulation with palmitic acid , significantly reduces high glucose-induced VSMC proliferation and migration . In contrast , suppression of PGC-1alpha by siRNA mimics the effects of glucose on VSMCs . Finally , mechanistic studies suggest that PGC-1alpha -mediated inhibition of VSMC proliferation and migration is regulated through preventing ERK1/2 PHOSphorylation . Conclusions/Significance These results indicate that PGC-1alpha is a key regulator of high glucose-induced proliferation and migration in VSMCs , and suggest that elevation of PGC-1alpha in VSMC could be a useful strategy in preventing the development of diabetic atherosclerosis .