TEAD1‐Mediated Trans‐Differentiation of Vascular Smooth Muscle Cells into Fibroblast‐Like Cells Contributes to the Stabilization and Repair of Disrupted Atherosclerotic Plaques
Abstract Atherosclerotic plaque rupture mainly contributes to acute coronary syndrome (ACS). Insufficient repair of these plaques leads to thrombosis and subsequent ACS. Central to this process is the modulation of vascular smooth muscle cells (VSMCs) phenotypes, emphasizing their pivotal role in at...
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202407408 |
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| author | Ming Zhai Zhijun Lei Yefei Shi Jiayun Shi Yanxi Zeng Shiyu Gong Weixia Jian Jianhui Zhuang Qing Yu Mark W. Feinberg Wenhui Peng |
| author_facet | Ming Zhai Zhijun Lei Yefei Shi Jiayun Shi Yanxi Zeng Shiyu Gong Weixia Jian Jianhui Zhuang Qing Yu Mark W. Feinberg Wenhui Peng |
| author_sort | Ming Zhai |
| collection | DOAJ |
| description | Abstract Atherosclerotic plaque rupture mainly contributes to acute coronary syndrome (ACS). Insufficient repair of these plaques leads to thrombosis and subsequent ACS. Central to this process is the modulation of vascular smooth muscle cells (VSMCs) phenotypes, emphasizing their pivotal role in atherosclerotic plaque stability and healing post‐disruption. Here, an expansion of FSP1+ cells in a tandem stenosis (TS) model of atherosclerotic mice is unveiled, predominantly originating from VSMCs through single‐cell RNA sequencing (scRNA‐seq) analyses and VSMC lineage tracing studies. Further investigation identified TEA domain transcription factor 1 (TEAD1) as the key transcription factor driving the trans‐differentiation of VSMCs into fibroblast‐like cells. In vivo experiments using a TS model of plaque rupture demonstrated that TEAD1 played a crucial role in promoting plaque stability and healing post‐rupture through pharmacological or TEAD1‐AAV treatments. Mechanistically, it is found that TEAD1 promoted the expression of fibroblast markers through the Wnt4/β‐Catenin pathway, facilitating the trans‐differentiation. Thus, this study illustrated that TEAD1 played a critical role in promoting the trans‐differentiation of VSMCs into fibroblast‐like cells and subsequent extracellular matrix production through the Wnt4/β‐Catenin pathway. Consequently, this process enhanced the healing mechanisms following plaque rupture, elucidating potential therapeutic avenues for managing atherosclerotic instability. |
| format | Article |
| id | doaj-art-f953193888024f838897401be0bbd02a |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-f953193888024f838897401be0bbd02a2025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202407408TEAD1‐Mediated Trans‐Differentiation of Vascular Smooth Muscle Cells into Fibroblast‐Like Cells Contributes to the Stabilization and Repair of Disrupted Atherosclerotic PlaquesMing Zhai0Zhijun Lei1Yefei Shi2Jiayun Shi3Yanxi Zeng4Shiyu Gong5Weixia Jian6Jianhui Zhuang7Qing Yu8Mark W. Feinberg9Wenhui Peng10Department of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University Shanghai 200072 ChinaDepartment of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University Shanghai 200072 ChinaDepartment of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University Shanghai 200072 ChinaDepartment of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University Shanghai 200072 ChinaDepartment of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University Shanghai 200072 ChinaDepartment of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University Shanghai 200072 ChinaDepartment of Endocrinology School of Medicine Xinhua Hospital Shanghai Jiaotong University Shanghai 200092 ChinaDepartment of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University Shanghai 200072 ChinaDepartment of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University Shanghai 200072 ChinaCardiovascular Division Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA 02115 USADepartment of Cardiology School of Medicine Shanghai Tenth People's Hospital Tongji University Shanghai 200072 ChinaAbstract Atherosclerotic plaque rupture mainly contributes to acute coronary syndrome (ACS). Insufficient repair of these plaques leads to thrombosis and subsequent ACS. Central to this process is the modulation of vascular smooth muscle cells (VSMCs) phenotypes, emphasizing their pivotal role in atherosclerotic plaque stability and healing post‐disruption. Here, an expansion of FSP1+ cells in a tandem stenosis (TS) model of atherosclerotic mice is unveiled, predominantly originating from VSMCs through single‐cell RNA sequencing (scRNA‐seq) analyses and VSMC lineage tracing studies. Further investigation identified TEA domain transcription factor 1 (TEAD1) as the key transcription factor driving the trans‐differentiation of VSMCs into fibroblast‐like cells. In vivo experiments using a TS model of plaque rupture demonstrated that TEAD1 played a crucial role in promoting plaque stability and healing post‐rupture through pharmacological or TEAD1‐AAV treatments. Mechanistically, it is found that TEAD1 promoted the expression of fibroblast markers through the Wnt4/β‐Catenin pathway, facilitating the trans‐differentiation. Thus, this study illustrated that TEAD1 played a critical role in promoting the trans‐differentiation of VSMCs into fibroblast‐like cells and subsequent extracellular matrix production through the Wnt4/β‐Catenin pathway. Consequently, this process enhanced the healing mechanisms following plaque rupture, elucidating potential therapeutic avenues for managing atherosclerotic instability.https://doi.org/10.1002/advs.202407408ACSatherosclerotic plaqueplaque ruptureTEAD1thrombosis |
| spellingShingle | Ming Zhai Zhijun Lei Yefei Shi Jiayun Shi Yanxi Zeng Shiyu Gong Weixia Jian Jianhui Zhuang Qing Yu Mark W. Feinberg Wenhui Peng TEAD1‐Mediated Trans‐Differentiation of Vascular Smooth Muscle Cells into Fibroblast‐Like Cells Contributes to the Stabilization and Repair of Disrupted Atherosclerotic Plaques Advanced Science ACS atherosclerotic plaque plaque rupture TEAD1 thrombosis |
| title | TEAD1‐Mediated Trans‐Differentiation of Vascular Smooth Muscle Cells into Fibroblast‐Like Cells Contributes to the Stabilization and Repair of Disrupted Atherosclerotic Plaques |
| title_full | TEAD1‐Mediated Trans‐Differentiation of Vascular Smooth Muscle Cells into Fibroblast‐Like Cells Contributes to the Stabilization and Repair of Disrupted Atherosclerotic Plaques |
| title_fullStr | TEAD1‐Mediated Trans‐Differentiation of Vascular Smooth Muscle Cells into Fibroblast‐Like Cells Contributes to the Stabilization and Repair of Disrupted Atherosclerotic Plaques |
| title_full_unstemmed | TEAD1‐Mediated Trans‐Differentiation of Vascular Smooth Muscle Cells into Fibroblast‐Like Cells Contributes to the Stabilization and Repair of Disrupted Atherosclerotic Plaques |
| title_short | TEAD1‐Mediated Trans‐Differentiation of Vascular Smooth Muscle Cells into Fibroblast‐Like Cells Contributes to the Stabilization and Repair of Disrupted Atherosclerotic Plaques |
| title_sort | tead1 mediated trans differentiation of vascular smooth muscle cells into fibroblast like cells contributes to the stabilization and repair of disrupted atherosclerotic plaques |
| topic | ACS atherosclerotic plaque plaque rupture TEAD1 thrombosis |
| url | https://doi.org/10.1002/advs.202407408 |
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