Resveratrol Inhibits Phenotype Modulation by Platelet Derived Growth Factor-bb in Rat Aortic Smooth Muscle Cells

Abstract

Dedifferentiated vascular smooth muscle cells (VSMCs) are phenotypically modulated from the contractile state to the active synthetic state in the vessel wall. In this study, we investigated the effects of resveratrol on phenotype modulation by dedifferentiation and the intracellular signal transduction pathways of platelet derived growth factor-bb (PDGF-bb) in rat aortic vascular smooth muscle cells (RAOSMCs). Treatment of RAOSMCs with resveratrol showed dose-dependent inhibition of PDGF-bb-stimulated proliferation. Resveratrol treatment inhibited this phenotype change and disassembly of actin filaments and maintained the expression of contractile phenotype-related proteins such as calponin and smooth muscle actin-alpha in comparison with only PDGF-bb stimulated RAOSMC. Although PDGF stimulation elicited strong and detectable Akt and mTOR phosphorylations lasting for several hours, Akt activation was much weaker when PDGF was used with resveratrol. In contrast, resveratrol only slightly inhibited phosphorylations of 42/44 MAPK and p38 MAPK. In conclusion, RAOSMC dedifferentiation, phenotype, and proliferation rate were inhibited by resveratrol via interruption of the balance of Akt, 42/44MAPK, and p38MAPK pathway activation stimulated by PDGF-bb.