Abstract
Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are essential for the development of hypertension. Insulin has been identified to promote VSMC proliferation and migration; resveratrol has been shown to have protective effects against cardiovascular diseases. This study aimed to investigate the effect of resveratrol on insulin-induced VSMC proliferation and migration and its potential mechanism. VSMC proliferation was measured by Cell Counting Kit-8 (CCK-8), cell counting method, and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Cell migration was detected by wound healing assay and transwell method. Expression of silent information regulator of transcription 1 (SIRT1) and phosphorylation levels of signaling molecules, such as phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt), in VSMCs were detected by Western blotting. Resveratrol (25-150 μM) was found to inhibit insulin-induced VSMC proliferation. Pretreatment with 100 μM resveratrol reduced insulin (100 nM)-mediated VSMC migration. LY294002, an inhibitor of PI3K, inhibited the stimulatory effect of insulin (100 nM) on the proliferation of VSMCs. Treatment with resveratrol also decreased insulin-induced stimulatory effect on PI3K and Akt phosphorylation levels. Moreover, resveratrol treatment increased SIRT1 protein expression in VSMCs. A SIRT1 inhibitor, EX527, reversed the inhibitory effect of resveratrol on insulin-induced VSMC proliferation and migration and activation of PI3K and Akt phosphorylation levels. In conclusion, our study revealed that treatment with resveratrol inhibited insulin-mediated VSMC proliferation and migration, possibly by activating SIRT1 and downregulating the PI3K/AKT pathway.