J Agric Food Chem. 2015 Jan 14;63(1):235-41. doi: 10.1021/jf505303s.
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.
原儿茶酸（PCA）被认为与动脉粥样硬化的进展有关。血管平滑肌细胞（VSMC）的增殖可能在动脉粥样硬化的发病机制中起关键作用。此外，5′-单磷酸腺苷激活的蛋白激酶（AMPK）对血管功能具有多种有益作用，并改善血管异常。本研究旨在确定 PCA 是否对油酸（OA）处理后的 VSMC 增殖具有抑制作用。用 OA（150 μM）或 OA 和 PCA（150 μg/mL）共同处理 A7r5 细胞 24 和 48 小时。发现 PCA 处理的细胞导致 G0/G1 细胞周期停滞增加。Western blot 显示，PCA 增加了 p53 和 p21Cip1 的表达，随后降低了细胞周期蛋白 E1 和 Cdk2 的表达。此外，PCA 诱导 OA 刺激后 AMPK 的磷酸化，并抑制脂肪酸合酶、Akt-p 和 Skp2 的表达。在用 AMPK 抑制剂处理后，上述 PCA 的作用被逆转。总之，PCA 通过激活 AMPK 和下调 FAS 和 AKT 信号来抑制 OA 诱导的 VSMC 增殖，从而阻止 G0/G1 期细胞周期进程。这些发现为 PCA 对 VSMC 的保护特性提供了新的见解，这可能构成一种新型有效的抗动脉粥样硬化药物。
