Substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cells

查看全文 作　　者：Mi [1]Hu;Fan [1]Jia;Wei-Pin [1]Huang;Xu [1]Li;Deng-Feng [1]Hu;Jing [1]Wang;Ke-Feng [1]Ren;Guo-Sheng [2]Fu;Yun-Bing [3]Wang;Jian [1]Ji

机构地区：[1]MOE Key Laboratory of Macromolecular Synthesis and Functionalization,Department of Polymer Science and Engineering,Zhejiang University,Hangzhou,310027,China;[2]Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province,Department of Cardiology,Sir Run Run Shaw Hospital,Zhejiang University,Hangzhou,310016,China;[3]National Engineering Research Center for Biomaterials,Sichuan University,Chengdu,610064,China

出　　处：《Bioactive Materials》索引2021年第6卷第5期,共10页

基　　金：supported by the National Natural Science Foundation of China(21875210);the National Key Research and Development Program of China(2016YFC1102203);the Natural Key Research and Development Project of Zhejiang Province(2018C03015);Zhejiang Provincial Ten Thousand Talents Program(2018R52001);the Fundamental Research Funds for the Central Universities(2020FZZX003-01-03);the Higher Education Discipline Innovation Project(111 Project)under Grant No.B16042. 摘　　要：Stiffening of blood vessels is one of the most important characteristics in the process of many cardiovascular pathologies such as atherosclerosis,angiosteosis,and vascular aging.Increased stiffness of the vascular extracellular matrix drives artery pathology and alters phenotypes of vascular cell.Understanding how substrate stiffness impacts vascular cell behaviors is of great importance to the biomaterial design in tissue engineering,regenerative medicine,and medical devices.Here we report that changing substrate stiffness has a significant impact on the autophagy of vascular endothelial cells(VECs)and smooth muscle cells(VSMCs).Interestingly,our findings demonstrate that,with the increase of substrate stiffness,the autophagy level of VECs and VSMCs showed differential changes:endothelial autophagy levels reduced,leading to the reductions in a range of gene expression associated with endothelial function;while,autophagy levels of VSMCs increased,showing a transition from contractile to the synthetic phenotype.We further demonstrate that,by inhibiting cell autophagy,the expressions of endothelial functional gene were further reduced and the expression of VSMC calponin increased,suggesting an important role of autophagy in response of the cells to the challenge of microenvironment stiffness changing.Although the underlying mechanism requires further study,this work highlights the relationship of substrate stiffness,autophagy,and vascular cell behaviors,and enlightening the design principles of surface stiffness of biomaterials in cardiovascular practical applications. 关键词：Substrate stiffness AUTOPHAGY Endothelial cells Smooth muscle cells Polyelectrolyte film

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Substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cells

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