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.
Highlights
Vascular smooth muscle cells (VSMC) exhibit differentiated, biosynthetic, contractile roles in the media layer of mature blood vessels
We investigated the effects of resveratrol on proliferation, phenotype modulation, and intracellular signal transduction pathways in Platelet derived growth factor-bb (PDGF-bb)-induced rat aortic vascular smooth muscle cells (RAOSMCs)
These results suggest that resveratrol exerts a potent antiproliferative effect on PDGF-bb-stimulated RAOSMC proliferation
Summary
Vascular smooth muscle cells (VSMC) exhibit differentiated, biosynthetic, contractile roles in the media layer of mature blood vessels. Differentiated VSMCs in normal vessels have a contractile phenotype, a spindle-like elongated morphology, and a smaller cell size. Dedifferentiated VSMCs in injured vessels have a synthetic phenotype, a hypertrophic appearance, hill and valley growth, and a relatively larger size. In addition to these morphological and functional alterations, the change in VSMCs from contractile to synthetic phenotype is controlled by SMC-specific molecular markers such as caldesmon, calponin, alpha-tropomysin, smooth muscle myosin heavy chain, SM22α, and smooth muscle alpha actin (αSMA) [4,5,6]. The mTOR protein has Oxidative Medicine and Cellular Longevity been implicated in cardiovascular diseases and in cardiac hypertrophy [10, 11]
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