Resveratrol Inhibits Restenosis through Suppressing Proliferation, Migration and Trans-differentiation of Vascular Adventitia Fibroblasts via Activating SIRT1

Abstract

Aim: After the balloon angioplasty, vascular adventitia fibroblasts (VAFs), which proliferate, trans-differentiate to myofibroblasts and migrate to neointima, are crucial in restenosis. Resveratrol (RSV) has been reported to protect the cardiovascular by reducing restenosis and the mechanism remains unclear. Methods: This study was dedicated to investigate the effect of RSV on VAFs in injured arteries and explore the potential mechanism. In this work, carotid artery balloon angioplasty was performed on male SD rats to ensure the injury of intima and VAFs were isolated to explore the effects in vitro. The functional and morphological results showed the peripheral delivery of RSV decreased restenosis of the injured arteries and suppressed the expression of proliferation, migration and transformation related genes. Moreover, after being treated with RSV, the proliferation, migration and trans-differentiation of VAFs were significantly suppressed and exogenous TGF-β1 can reverse this effect. Result: Mechanistically, RSV administration activated SIRT1 and decreased the translation and expression of TGF-β1, SMAD3 and NOX4, and reactive oxygen species (ROS) decreased significantly after VAFs treated with RSV. Conclusion: Above results indicated RSV inhibited restenosis after balloon angioplasty through suppressing proliferation, migration and trans-differentiation of VAFs via regulating SIRT1- TGF-β1-SMAD3-NOX4 to decrease ROS.