Uremia Serum Promotes the Proliferation of Human Aortic Smooth Muscle Cells through the ROS-NLRP3 Signaling Pathway and Participates in Neointimal Hyperplasia
Objective To explore the effect of ROS-NLRP3 signaling pathway on neointimal hyperplasia(NH)induced by chronic kidney disease(CKD)in vitro.Methods Human aortic smooth muscle cells(HASMCs)were cultured and divided into three groups:normal serum control(NC)group,uremia serum treatment group,uremia serum+Mito-TEMPO treatment group.The effects of uremia serum on HASMCs phenotype,oxidative stress level,expression levels of inflammatory factors and non-like receptor protein 3(NLRP3)inflammatory complex were detected by Western blot,immunofluorescence and ELISA assays.Results Compared to NC group,the proliferation of HASMCs,the protein expressions of α-SMA and calponin 1,the levels of mitochondrial reactive oxygen species(mtROS),and inflammatory factor IL-6,IL-18 and TNF-α,protein expressions of NLRP3,cysteinyl aspartate specific proteinase-1(caspase-1),cleaved caspase-1,IL-1β,and IL-18 were significantly increased(all P＜0.05),superoxide dismutase(SOD)activity was significantly decreased(all P＜0.05)after treatment of uremia serum.However,the proliferation of HASMCs,the protein expressions of α-SMA and calponin 1,levels of mtROS,inflammatory factor IL-6,IL-18 and TNF-α,and the protein expression levels of NLRP3,caspase-1,cleaved caspase-1,IL-1β,and IL-18 were significantly decreased(all P＜0.05),SOD activity was significantly increased(P＜0.05)in uremia serum+Mito-TEMPO treatment group.Conclusion Uremia serum can promote the proliferation of HASMCs in neointimal hyperplasia through ROS-NLRP3 signaling pathway.
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