CCDC80 Protects against Aortic Dissection and Rupture by Maintaining the Contractile Smooth Muscle Cell Phenotype
Abstract Aortic dissection (AD) is a life‐threatening medical emergency characterized by adverse vascular remodeling. Coiled‐coil domain‐containing protein 80 (CCDC80) plays an essential role in regulating cardiovascular remodeling. This study aims to define the role of CCDC80 in the formation and d...
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Wiley
2025-07-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202502108 |
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| author | Qingqing Xiao Yi Li Bin Cai Xiying Huang Liang Fang Feng Liang Long Chen Ke Xu Weifeng Zhang Xiaolei Wang Anwen Yin Xia Wang Zhaohua Cai Fei Zhuang Qin Shao Bin Zhou Berthold Hocher Ben He Linghong Shen |
| author_facet | Qingqing Xiao Yi Li Bin Cai Xiying Huang Liang Fang Feng Liang Long Chen Ke Xu Weifeng Zhang Xiaolei Wang Anwen Yin Xia Wang Zhaohua Cai Fei Zhuang Qin Shao Bin Zhou Berthold Hocher Ben He Linghong Shen |
| author_sort | Qingqing Xiao |
| collection | DOAJ |
| description | Abstract Aortic dissection (AD) is a life‐threatening medical emergency characterized by adverse vascular remodeling. Coiled‐coil domain‐containing protein 80 (CCDC80) plays an essential role in regulating cardiovascular remodeling. This study aims to define the role of CCDC80 in the formation and development of AD. Significant downregulation of CCDC80 in vascular smooth muscle cell (VSMC) in human and mouse AD is identified. Then, CCDC80 knockout mice (CCDC80−/−) and VSMC‐specific CCDC80 knockout mice (CCDC80fl/fl SM22α Cre+) treated with angiotensin II (Ang II) or Ang II combined with β‐aminopropionitrile monofumarate (BAPN) frequently develop AD with higher frequency and severity, accompanied by severe elastin fragmentation and collagen deposition. Mechanistically, CCDC80 interacts with JAK2, and CCDC80 deficiency promotes VSMC phenotype switching, proliferation, and migration as well as matrix metalloproteinase production by activating the JAK2/STAT3 signaling pathway. Moreover, the JAK2/STAT3 pathway‐specific inhibitor ameliorates adverse vascular remodeling and reduces AD formation in CCDC80‐knockout mice by mitigating VSMC phenotype switching. In conclusion, CCDC80 deficiency exacerbates the progression of events leading to AD by activating the JAK2/STAT3 pathway involved in regulating the phenotype switching and function of VSMCs. These findings highlight that CCDC80 is a potential key target for the prevention and treatment of AD. |
| format | Article |
| id | doaj-art-37d6eaef56e94e0799745ce65fd60c55 |
| institution | Matheson Library |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-37d6eaef56e94e0799745ce65fd60c552025-07-18T08:25:54ZengWileyAdvanced Science2198-38442025-07-011226n/an/a10.1002/advs.202502108CCDC80 Protects against Aortic Dissection and Rupture by Maintaining the Contractile Smooth Muscle Cell PhenotypeQingqing Xiao0Yi Li1Bin Cai2Xiying Huang3Liang Fang4Feng Liang5Long Chen6Ke Xu7Weifeng Zhang8Xiaolei Wang9Anwen Yin10Xia Wang11Zhaohua Cai12Fei Zhuang13Qin Shao14Bin Zhou15Berthold Hocher16Ben He17Linghong Shen18Department of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Rheumatology Peking Union Medical College Hospital Peking Union Medical College & Chinese Academy of Medical Sciences Beijing 100730 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiac Surgery Shanghai Chest Hospital Shanghai Jiaotong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaChinese Academy of Sciences University of Chinese Academy of Sciences Shanghai 200032 ChinaFifth Department of Medicine (Nephrology/Endocrinology/Rheumatology/Pneumology) University Medical Centre Mannheim University of Heidelberg 69123 Heidelberg GermanyDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaDepartment of Cardiology Shanghai Chest Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200030 ChinaAbstract Aortic dissection (AD) is a life‐threatening medical emergency characterized by adverse vascular remodeling. Coiled‐coil domain‐containing protein 80 (CCDC80) plays an essential role in regulating cardiovascular remodeling. This study aims to define the role of CCDC80 in the formation and development of AD. Significant downregulation of CCDC80 in vascular smooth muscle cell (VSMC) in human and mouse AD is identified. Then, CCDC80 knockout mice (CCDC80−/−) and VSMC‐specific CCDC80 knockout mice (CCDC80fl/fl SM22α Cre+) treated with angiotensin II (Ang II) or Ang II combined with β‐aminopropionitrile monofumarate (BAPN) frequently develop AD with higher frequency and severity, accompanied by severe elastin fragmentation and collagen deposition. Mechanistically, CCDC80 interacts with JAK2, and CCDC80 deficiency promotes VSMC phenotype switching, proliferation, and migration as well as matrix metalloproteinase production by activating the JAK2/STAT3 signaling pathway. Moreover, the JAK2/STAT3 pathway‐specific inhibitor ameliorates adverse vascular remodeling and reduces AD formation in CCDC80‐knockout mice by mitigating VSMC phenotype switching. In conclusion, CCDC80 deficiency exacerbates the progression of events leading to AD by activating the JAK2/STAT3 pathway involved in regulating the phenotype switching and function of VSMCs. These findings highlight that CCDC80 is a potential key target for the prevention and treatment of AD.https://doi.org/10.1002/advs.202502108aortic dissectionCCDC80JAK2/STAT3 signaling pathwayvascular remodelingVSMC phenotype switching |
| spellingShingle | Qingqing Xiao Yi Li Bin Cai Xiying Huang Liang Fang Feng Liang Long Chen Ke Xu Weifeng Zhang Xiaolei Wang Anwen Yin Xia Wang Zhaohua Cai Fei Zhuang Qin Shao Bin Zhou Berthold Hocher Ben He Linghong Shen CCDC80 Protects against Aortic Dissection and Rupture by Maintaining the Contractile Smooth Muscle Cell Phenotype Advanced Science aortic dissection CCDC80 JAK2/STAT3 signaling pathway vascular remodeling VSMC phenotype switching |
| title | CCDC80 Protects against Aortic Dissection and Rupture by Maintaining the Contractile Smooth Muscle Cell Phenotype |
| title_full | CCDC80 Protects against Aortic Dissection and Rupture by Maintaining the Contractile Smooth Muscle Cell Phenotype |
| title_fullStr | CCDC80 Protects against Aortic Dissection and Rupture by Maintaining the Contractile Smooth Muscle Cell Phenotype |
| title_full_unstemmed | CCDC80 Protects against Aortic Dissection and Rupture by Maintaining the Contractile Smooth Muscle Cell Phenotype |
| title_short | CCDC80 Protects against Aortic Dissection and Rupture by Maintaining the Contractile Smooth Muscle Cell Phenotype |
| title_sort | ccdc80 protects against aortic dissection and rupture by maintaining the contractile smooth muscle cell phenotype |
| topic | aortic dissection CCDC80 JAK2/STAT3 signaling pathway vascular remodeling VSMC phenotype switching |
| url | https://doi.org/10.1002/advs.202502108 |
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