Substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cells
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 cel...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2021-05-01
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| Series: | Bioactive Materials |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452199X20302656 |
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| author | Mi Hu Fan Jia Wei-Pin Huang Xu Li Deng-Feng Hu Jing Wang Ke-Feng Ren Guo-Sheng Fu Yun-Bing Wang Jian Ji |
| author_facet | Mi Hu Fan Jia Wei-Pin Huang Xu Li Deng-Feng Hu Jing Wang Ke-Feng Ren Guo-Sheng Fu Yun-Bing Wang Jian Ji |
| author_sort | Mi Hu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T08:17:14Z |
| format | Article |
| id | doaj.art-83b262cd3ee74ad4af82fff8fea31043 |
| institution | Directory Open Access Journal |
| issn | 2452-199X |
| language | English |
| last_indexed | 2024-04-24T08:17:14Z |
| publishDate | 2021-05-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Bioactive Materials |
| spelling | doaj.art-83b262cd3ee74ad4af82fff8fea310432024-04-17T03:18:44ZengKeAi Communications Co., Ltd.Bioactive Materials2452-199X2021-05-016514131422Substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cellsMi Hu0Fan Jia1Wei-Pin Huang2Xu Li3Deng-Feng Hu4Jing Wang5Ke-Feng Ren6Guo-Sheng Fu7Yun-Bing Wang8Jian Ji9MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, China; Corresponding author.Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, 310016, China; Corresponding author.National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, ChinaMOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, 310027, ChinaStiffening 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.http://www.sciencedirect.com/science/article/pii/S2452199X20302656Substrate stiffnessAutophagyEndothelial cellsSmooth muscle cellsPolyelectrolyte film |
| spellingShingle | Mi Hu Fan Jia Wei-Pin Huang Xu Li Deng-Feng Hu Jing Wang Ke-Feng Ren Guo-Sheng Fu Yun-Bing Wang Jian Ji Substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cells Bioactive Materials Substrate stiffness Autophagy Endothelial cells Smooth muscle cells Polyelectrolyte film |
| title | Substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cells |
| title_full | Substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cells |
| title_fullStr | Substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cells |
| title_full_unstemmed | Substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cells |
| title_short | Substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cells |
| title_sort | substrate stiffness differentially impacts autophagy of endothelial cells and smooth muscle cells |
| topic | Substrate stiffness Autophagy Endothelial cells Smooth muscle cells Polyelectrolyte film |
| url | http://www.sciencedirect.com/science/article/pii/S2452199X20302656 |
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