心脑血管病防治2024，Vol.24Issue(10)：5-9,18,6.DOI:10.3969/j.issn.1009-816x.2024.10.002
冠心宁通过TNFAIP3-ASK1/JNK通路对动脉粥样硬化血管平滑肌细胞表型转换的调控作用
Regulatory effect of Guanxinning on phenotypic transformation of atherosclerotic vascular smooth muscle cells through tumor necrosis factor α-induced protein 3-apoptosis signal-regulating kinase 1/c-Jun N-terminal kinase pathway
摘要
Abstract
Objective To explore the molecular mechanism of Guanxinning(GXN)regulating the stability of atherosclerotic(AS)plaques.Methods Serum containing GXN was prepared.Vascular smooth muscle cells(VSMCs)induced with oxidized low-density lipoprotein(ox-LDL)were used to construct the in vitro AS model.The phenotypic transformation of VSMCs was detected by Western blot and qPCR.The effect of GXN on VSMCs phenotypic transformation was examined by silencing tumor necrosis factor α-induced protein 3(TNFAIP3).In addition,an apoptosis signal-regulating kinase 1(ASK1)overexpression vector was constructed and transfected into cells with Lip3000 to detect whether GXN exerts its effects through the ASK1/c-Jun N-terminal kinase(ASK1/JNK)pathway.Results Compared with the control group,the ox-LDL group showed a phenotypic transformation of cells characterized by decreased expression levels of type I collagen(COLIA1 and COLIA2)and α-smooth muscle actin(α-SMA)(all P<0.01),and increased expression levels of matrix metalloproteinases(MMP)2,MMP9,MMP13,osteopontin(OPN),TNFAIP3,phosphorylated ASK1/ASK1 ratio(p-ASK1/ASK1),and phosphorylated JNK/JNK ratio(p-JNK/JNK)(all P<0.01).After GXN treatment,VSMCs transformed to a contractile phenotype,indicated by increased levels of COLIA1,COLIA2,TNFAIP3 and α-SMA compared to the ox-LDL group(all P<0.01),and decreased levels of MMP2,MMP9,MMP13,OPN,p-ASK1/ASK1,and p-JNK/JNK(all P<0.01).After TNFAIP3 silencing,compared to the ox-LDL+10%GXN+sh-NC group,the levels of COLIA1,COLIA2,TNFAIP3 and α-SMA decreased(all P<0.01),while the expression levels of MMP2,MMP9,MMP13,OPN,p-ASK1/ASK1,and p-JNK/JNK increased(all P<0.01).Overexpression of ASK1 resulted in decreased levels of COLIA1,COLIA2 and α-SMA(all P<0.01),and increased expression levels of MMP2,MMP9,MMP13,OPN,p-ASK1/ASK1,and p-JNK/JNK compared to the ox-LDL+10%GXN+oe-NC group(all P<0.01).Conclusion GXN may stabilize atherosclerotic plaques by regulating the phenotypic transformation of VSMCs through the TNFAIP3-ASK1/JNK pathway.关键词
冠心宁/动脉粥样硬化斑块/肿瘤坏死因子α诱导蛋白3/凋亡信号调节激酶1/c-Jun氨基末端激酶通路/血管平滑肌细胞Key words
Guanxinning/Atherosclerotic plaque/Tumor necrosis factor α-induced protein 3/Apoptosis signal-regulating kinase 1/c-Jun N-terminal kinase pathway/Vascular smooth muscle cells引用本文复制引用
毛萍,吕方超,徐晨凯,唐礼江..冠心宁通过TNFAIP3-ASK1/JNK通路对动脉粥样硬化血管平滑肌细胞表型转换的调控作用[J].心脑血管病防治,2024,24(10):5-9,18,6.基金项目
浙江省医学会临床医学科研专项基金(2022ZYC-Z14) （2022ZYC-Z14）
