SCOPE: Diabetes is a critical factor for atherosclerosis, as hyperglycemia induces vascular smooth muscle cell (VSMC) proliferation and migration and subsequently contributes to the formation of atherosclerotic lesions. This study investigates whether resveratrol plays a regulatory role in the proliferation and migration of VSMCs under high glucose induction to imitate a hyperglycemic condition. METHODS AND RESULTS: Resveratrol inhibited the migration of VSMCs in the wound-healing assay and the formation of lamellipodia and filopodia as assessed by atomic force microscopy scanning. Resveratrol suppressed the mRNA expression of c-Src, Rac1, cdc42, IRS-1, MEKK1, MEKK4, and mitogen-activated protein kinase along with the protein levels of c-Src, p-Src, and cdc42 in VSMCs. Resveratrol decreased the level of p-FAK protein under normal glucose conditions. Resveratrol could inhibit the activities of matrix metalloproteinase (MMP) 2 and MMP 9 as shown by zymography. Moreover, resveratrol also regulated the mitogen-activated protein kinase pathway and MMP activities of VSMC migration under the high glucose condition. CONCLUSION: The antimigratory effects of resveratrol by reduced MMP expression through the inhibition of Rac1, p-FAK, and lamellipodia formation and the activation of p-AKT and p-ERK1/2 suggest that resveratrol is a potential compound for the treatment of vascular diseases via the regulation of VSMC migration.
SCOPE: Diabetes is a critical factor for atherosclerosis, as hyperglycemia induces vascular smooth muscle cell (VSMC) proliferation and migration and subsequently contributes to the formation of atherosclerotic lesions. This study investigates whether resveratrol plays a regulatory role in the proliferation and migration of VSMCs under high glucose induction to imitate a hyperglycemic condition. METHODS AND RESULTS:Resveratrol inhibited the migration of VSMCs in the wound-healing assay and the formation of lamellipodia and filopodia as assessed by atomic force microscopy scanning. Resveratrol suppressed the mRNA expression of c-Src, Rac1, cdc42, IRS-1, MEKK1, MEKK4, and mitogen-activated protein kinase along with the protein levels of c-Src, p-Src, and cdc42 in VSMCs. Resveratrol decreased the level of p-FAK protein under normal glucose conditions. Resveratrol could inhibit the activities of matrix metalloproteinase (MMP) 2 and MMP 9 as shown by zymography. Moreover, resveratrol also regulated the mitogen-activated protein kinase pathway and MMP activities of VSMC migration under the high glucose condition. CONCLUSION: The antimigratory effects of resveratrol by reduced MMP expression through the inhibition of Rac1, p-FAK, and lamellipodia formation and the activation of p-AKT and p-ERK1/2 suggest that resveratrol is a potential compound for the treatment of vascular diseases via the regulation of VSMC migration.