Ting-Tsz Ou, Ming-Cheng Lin, Cheng-Hsun Wu, Wea-Lung Lin and Chau-Jong Wang Pages 3944 - 3953 ( 10 )
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.
Vascular smooth muscle cells, proliferation, gallic acid, oleic acid, AMP-activated protein kinase (AMPK), eNOS.
, , , , Institute of Biochemistry and Biotechnology, College of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Jianguo N. Road, Taichung 402, Taiwan.