层流切应力通过上调自噬水平抑制氧化型低密度脂蛋白诱导的内皮祖细胞损伤作用
Protective effect of shearstress on LDL-induced endothelial progenitor cell injury through up-regulation of autophagy
陈丽芳 1黄于朗 1陈俊羽 2罗新林2
作者信息
- 1. 深圳市前海蛇口自贸区医院心内科,深圳 518067
- 2. 中国医学科学院阜外医院深圳医院心内科,深圳 518057
- 折叠
摘要
目的:分析层流切应力(LSS)对氧化型低密度脂蛋白(ox-LDL)诱导内皮祖细胞(EPCs)损伤的保护机制.方法:通过CCK8分析EPCs中ox-LDL和LSS的处理条件;Transwell和成管实验分析LSS对ox-LDL处理前后EPCs细胞迁移和成管能力的影响;Western检测LSS和ox-LDL处理对细胞自噬、内皮-间质转化标志物的影响;Western分析自噬激活和抑制剂对ox-LDL和LSS处理后自噬、内皮-间质转化标志物的影响.结果:ox-LDL处理后EPCs细胞的增殖能力,迁移能力和成管能力均下调,LSS处理后显著升高,LSS处理对ox-LDL诱导的EPCs细胞损伤有保护作用.分子机制方面,LSS处理后EPCs细胞自噬水平升高.ox-LDL处理后EPCs细胞发生显著的内皮间质化转变,LSS处理可明显抑制这一过程.自噬激活剂和抑制剂验证了这些结果.结论:LSS可通过上调自噬水平抑制ox-LDL诱导的EPCs内皮间质化,对EPCs细胞起保护作用.
Abstract
Objective To analyze the protective mechanism of laminar shear stress(LSS)on endothelial progenitor cells(EPCs)injury induced by oxidized low-density lipoprotein(ox-LDL).Methods The treatment conditions of ox-LDL and LSS in EPCs were analyzed by CCK8.The effects of LSS on the migration and tube formation ability of EPCs before and after treat-ment with ox-LDL were analyzed by Transwell and tube formation experiments.The effects of LSS and ox-LDL treatment on autophagy and endothelial-mesenchymal transition markers were analyzed by Western blot.The effects of autophagy activa-tors and inhibitors on autophagy and endothelial-mesenchymal transition markers after treatment with ox-LDL and LSS were analyzed by Western blot.Results After treatment with ox-LDL,the proliferation,migration,and tube formation ability of EPCs were down-regulated,and LSS treatment significantly increased them.LSS treatment had a protective effect on ox-LDL-induced EPCs cell injury.In terms of molecular mechanisms,LSS treatment increased the autophagy level of EPCs cells.After treatment with ox-LDL,EPCs cells underwent significant endothelial mesenchymal transition,which was significantly inhibited by LSS treatment.Autophagy activators and inhibitors confirmed these results.Conclusion LSS can inhibit ox-LDL-induced endothelial mesenchymal transformation of EPCs by upregulating autophagy,and plays a protective role in EPCs.
关键词
层流切应力/内皮祖细胞(EPCs)损伤/细胞自噬Key words
laminar shear stress/endothelial progenitor cell(EPCs)injury/autophagy引用本文复制引用
基金项目
深圳市南山区卫生科技计划项目(2020007)
深圳市南山区卫生科技计划项目(202034)
深圳市三名工程资助院级项目(YJ20210007)
出版年
2024