Role of peroxisome proliferators-activated receptor-gamma in phenotypic transforming of vascular smooth muscle cells in hypertension / 第三军医大学学报

ABSTRACT

Objective To observe the effect of peroxisome proliferators activated receptor gamma(PPAR-?)on phenotypic transforming of vascular smooth muscle cells(VSMC)in hypertension.Methods Spontaneous hypertension rats(SHR)and WKY rats both aged 4 months were included.SHR rats as well as WKY rats were divided to be fed with normal chow,and chow added with rosiglitazone(10 mg?kg-1?d-1)for 16 weeks.VSMC were isolated from SHR rats and WKY rats and cultured by patch-attaching method,then respectively divided into 3 groups after treated with genetic recombination technology:normal VSMC,PPAR? overexpressed VSMC and PPAR? silenced VSMC.Expressions of OPN and ?-SMA,which respectively represent the undifferentiated and differentiated VSMC,were detected by Western blotting.Cell proliferation was determined by detecting DNA synthesis and cell counting.The changes of arteries were evaluated pathologically.Results Rosiglitazone decreased blood pressure and ameliorated vascular remodeling of aorta in SHR rats.Aorta of SHR showed an upregulation of OPN and downregulation of ?-SMA,which could be inhibited by rosiglitazone.VSMC from SHR rats showed an upregulation of OPN and downregulation of ?-SMA,and increased cell proliferation.These changes were all inhibited by rosiglitazone.In the cells that overexpressed PPAR?,the cell proliferation rate was lower,and the expressions of OPN and ?-SMA were depressed,compared with the corresponding control cells.Conclusion PPAR-? could inhibit the phenotypic transforming of VSMC,and this might be responsible for the amelioration of vascular remodeling in hypertension.