Gallic Acid Attenuates Oleic Acid-induced Proliferation of Vascular Smooth Muscle Cell Through Regulation of AMPK-eNOS-FAS Signaling

Abstract

Vascular smooth muscle cell (VSMC) proliferation plays a central role in the pathogenesis of obesity-related atherosclerosis. The molecular mechanism of GA on oleic acid (OA)-induced proliferation of vascular smooth muscle cell is evaluated. Cells were treated with OA (150 μM), or co-treated with OA and GA (10-30 μM) for 48 h, MTT assay was performed for proliferation. Using flow cytometry analysis, the GA-treated cells caused an increase in G2/M phase. A decrease in cyclin B1 and cyclin-dependent kinase 1 (cdc2) and increase in kip/p27 and cip1/p21 were found by western blotting. Additional mechanistic studies showed that GA induced the activation of AMP-activated protein kinase (AMPK) and eNOS and the inhibition of fatty acid synthase (FAS) after stimulation with OA. Furthermore, the addition of compound C, a specific inhibitor of AMPK, reduced the activation of GA-mediated eNOS and NO production and increased the proliferation of cells. Inhibition of NOS by L-NAME had no further effect on VSMC proliferation. The present results indicate that GA was an effected and anti-atherogenic agent in VSMC. It attenuates cell cycle progression via AMPKmediated eNOS activation, which results in the production of NO and prevents atherosclerosis.