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.
Keywords: Vascular smooth muscle cells, proliferation, gallic acid, oleic acid, AMP-activated protein kinase (AMPK), eNOS.
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