Inhibition of oxidized-phospholipid-induced vascular smooth muscle cell proliferation by resveratrol is associated with reducing Cx43 phosphorylation.

Abnormal proliferation of vascular smooth muscle cells (VSMCs) is an important factor during the progression of atherosclerosis. In this study, we investigated the effects of resveratrol on atherosclerosis-associated proliferation of VSMCs. We utilized an oxidized phospholipid, 1-palmitoyl-2-oxovaleroyl-sn-glycero-3-phosphorylcholine (POVPC) to induce abnormal proliferation of VSMCs. Our results showed the treatments with resveratrol dose-dependently abolished POVPC-induced VSMC proliferation, as evidenced by the decreased [(3)H]thymidine incorporated into VSMCs and reduced percentage of 5-ethynyl-2'-deoxyuridine (EdU)-positive VSMCs. Cell cycle analysis demonstrated that resveratrol inhibited POVPC-induced increase in the S phase cell population and DNA synthesis. Our study further indicated that POVPC-induced VSMC proliferation was associated with a significant increase in the phosphorylation of Cx43, which was a consequence of activation of MAPK signaling. Interestingly, treatment with resveratrol abolished POVPC-induced phosphorylation of Cx43 as a result of inhibiting activation of Src, MEK, and ERK1/2. Our results provided a novel mechanism by which resveratrol may contribute to cardiovascular protection.