Hypomethylation of osteopontin Promoter and phenotype switching of vascular smooth muscle cells in great saphenous varicose veins / 中华普通外科杂志

Objective To investigate the relationship between abnormal methylation in promoter regions for OPN and VSMC phenotype switching in varicosity.Methods Immunohistochemistry and Western-blot were used to evaluate the expression of SMA and OPN in VSMC.Methylation-specific PCR was used to evaluate the methylation level of OPN in VSMC of vein samples.Ultrastructure change of VSMC was observed by transmission electron microscope (TEM).Results Compared to normal vein,OPN in VSMCs were significantly highly expressed,mainly in the neointimal region (P ＜ 0.01).SMA in neointima region was in low expression (P ＜ 0.01).The density of OPN in varicose group was significantly higher (P ＜0.01).DNA methylation level of OPN was lower in varicose veins.Conclusions Hypomethylation of the promoter regions for OPN may cause high expression of OPN leading to VSMC phenotype switching and development of varicosity.

Regulatory mechanism of vascular smooth muscle cell phenotype switch in aortic disease: An update / 第二军医大学学报

Aortic disease (AD) consists of a series of life-threatening diseases caused by aortic wall lesions. Up to now little has been known about the etiology of non-hereditary AD. Vascular smooth muscle cells (VSMC) are the major components of the medial aortic wall and can toggle between a contractile phenotype and a synthetic phenotype. The excessive transformation of VSMC from contractile state to synthetic state plays an important role in the development and progression of AD. Although there are many researches on the regulation of VSMS phenotype switch, how these regulatory pathways operate harmoniously and the what relationship between them remain to be elucidated. Here in this paper we reviewed the existing regulatory mechanisms of VSMC phenotype switch.

1,25(OH)2D3 promotes M1 macrophage switching to M2 via VDR-PPARγ pathway induced by high glucose / 中华肾脏病杂志

Objective To investigate the effect of 1,25(OH)2D3 on high glucose induced macrophage activation and its underlying signal transduction mechanism.Methods RAW 264.7 cells were used to perform cell culture,the activity of intracellular iNOS was measured.VDR siRNA and PPARγ antagonist pre-treatment with macrophages were done before using 10-8 mol/L1,25(OH)2D3 to intervene high glucose pre-incubated macrophages.M1 markers including iNOS,TNF-α,IL-12,M2 markers including MR,Arg-1,IL-10 and nuclear receptors VDR and PPARγ were separately examined.Results The iNOS activity was increased in a glucose-dose and time dependent manner.Particularly,25 mmol/L glucose at 24 h gave the maximum response.After being treated with 25 mmol/L glucose for 24 h,not only inflammatory cytokines of TNF-α,IL-12 in the supernatant were increased,but quantitative real-time PCR and Western blotting analysis showed iNOS was also up-regulated (P ＜ 0.05).However,M2 markers,i.e.MR and Arg-l were significantly decreased (P ＜ 0.05).When in the presence of 1,25(OH),D3,the trends were reversed:the markers of M1,including TNF-α,IL-12 and iNOS were obviously reduced (P ＜ 0.05),while M2 markers,IL-10,Arg-1 and MR were increased (P ＜ 0.05).In addition,VDR and PPARγ were also increased (P ＜ 0.05).However,the above effects of 1,25 (OH)2D3 were abolished when further inhibited the expression of VDR and PPARγby VDR siRNA and PPARγ antagonist.Besides,accompanied by VDR,PPARγwas also decreased upon the treatment with VDR siRNA (P ＜ 0.05).Conclusion 1,25(OH)2D3 can promote high glucose induced classically activated macrophages (M1) converting to alternatively activated macrophages (M2) and this is achieved through VDR-PPARγ pathway.