Abstract:Aim To investigate the phenotypic modulation and proliferation changes of vascular smooth muscle cell(VSMC)and vascular adventitia fibroblasts(VAF)in the vein graft restenosis model.To evaluate the effects of the phenotypic modulation and proliferation changes of VSMC and VAF in vascular remodeling.Methods To create the pig autogenous vein grafts restenosis model,specimens were harvested at three time points that was 7th,14th and 30th day.Histomorphometrical and immunohistochemical approach were used to detect the changes of vascular remodeling and the expression of proliferation cell nuclear(PCNA),smooth muscle α-actin(SM-α-actin)and osteopontin(OPN).Results ①At 7th day after operation,the neointima formed and continuously thickened,whose thickness reached maximum at 30th day postoperation.Internal elastic lamina(IELA)gradually decreased after operation,and at 30th day group luminal area reduced minimally(P<0.05).Remodeling index and external elastic lamina(EELA)slightly increased at 7th day group,but reduced gradually after that,which at 14th day and 30th day group decreased distinctly(P<0.05).②According to PCNA stain,the proliferation index of VAF and VSMC increased significantly at 7th day after operation,which reached peak at 14th day,whereas the expression of PCNA reverted toward the baseline at 30th day after operation.③According to SM-α-actin stain,at 7th day after operation,the positive cell area decreased in the medium,but adventitia and neointimal were positive;At 14th day,the positive cell area decreased significantly in the medium,however,the positive area of adventitia and neointimal increased significantly;At 30th day positive expression of the medium recovered gradually,and the positive area of adventitia was less than that at 14th day,but the positive expression in the neointimal has no significant changes compared with 14th day.④OPN stain showed that the positive expression was significant in the medium at 7th day after operation.At 14th day,the positive expression of VSMC was less than that at 7th day in the medium,but that of neointimal increased significantly,which reached peak.At 30th day,there was a less positive part of VSMC in the medium,and the positive expression of VSMC in the neointimal decreased significantly compared with 14th day.OPN was negative in adventitia at different time after operation.Conclusion The phenotypic modulation and proliferation changes of VSMC and VAF are the important factors on vascular remodeling,which takes part in and accelerates the course of vein restenosis.