Protocatechuic acid inhibits oleic acid-induced vascular smooth muscle cell proliferation through activation of AMP-activated protein kinase and cell cycle arrest in G0/G1 phase.

Protocatechuic acid (PCA) has been implicated in the progression of atherosclerosis. The proliferation of vascular smooth muscle cells (VSMC) may play a crucial role in the pathogenesis of atherosclerosis. Adenosine 5′-monophosphate-activated protein kinase (AMPK) additionally exerts several beneficial effects on vascular function and improves vascular abnormalities. The current study sought to determine whether PCA has an inhibitory effect on VSMC proliferation under oleic acid (OA) treatment. A7r5 cells were treated with OA (150 μM) or cotreated with OA and PCA (150 μg/mL) for 24 and 48 h. PCA-treated cells were found to cause an increase in G0/G1 cell cycle arrest. Western blotting showed that PCA increased the expressions of p53 and p21Cip1, subsequently decreasing the expression of cyclin E1 and Cdk2. In addition, PCA induced phosphorylation of AMPK and inhibited the expression of fatty acid synthase, Akt-p, and Skp2 after stimulation with OA. After treatment with AMPK inhibitor, the effects of PCA mentioned above were reversed. Taken together, PCA inhibited OA-induced VSMC proliferation through AMPK activation and down-regulation of FAS and AKT signals, which then blocks G0/G1 phase cell cycle progression. These findings provide a new insight into the protective properties of PCA on VSMC, which may constitute a novel effective antiatherosclerosis agent.