Calpain‐2‐Mediated Endothelial Focal Adhesion Disruption in Thoracic Aortic Dissection
Abstract Thoracic aortic dissection (TAD) is a life‐threatening condition with high mortality rates. Recent research suggests a potential link between early‐stage TAD and endothelial barrier dysfunction, although the underlying mechanisms remain unclear. Single‐cell RNA sequencing data from patients...
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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.202501112 |
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| author | Xiaomei Teng Yansong Wang Haoyue Huang Yinglong Ding Jun Wang Meili Liu Kun Song Lianbo Shao You Yu Ziying Yang Zhenya Shen |
| author_facet | Xiaomei Teng Yansong Wang Haoyue Huang Yinglong Ding Jun Wang Meili Liu Kun Song Lianbo Shao You Yu Ziying Yang Zhenya Shen |
| author_sort | Xiaomei Teng |
| collection | DOAJ |
| description | Abstract Thoracic aortic dissection (TAD) is a life‐threatening condition with high mortality rates. Recent research suggests a potential link between early‐stage TAD and endothelial barrier dysfunction, although the underlying mechanisms remain unclear. Single‐cell RNA sequencing data from patients reveal that dysregulated Calpain‐2 expression modulates endothelial focal adhesion proteins, serving as an early pathological hallmark and driver of TAD. Elevated plasma calpain activity is strongly associated with an increased risk of TAD and organ dysfunction. Both endogenous and exogenous calpain inhibitors effectively prevent TAD onset and progression in murine models induced by β‐aminopropionitrile (BAPN). In early TAD, endothelial junction integrity in the ascending aorta and aortic arch is compromised. Endothelial‐specific deletion of Capns1 mitigates early and sustained endothelial focal adhesion damage by reducing aberrant expression of Integrin alpha‐V(Itgav), vinculin, and talin‐1, thereby decreasing TAD incidence. In contrast, macrophage‐specific Capns1 knockout does not impact TAD development but accelerates aortic dissection rupture in later stages. Mechanistically, angiotensin II upregulates Calpain‐2, leading to endothelial focal adhesion activation through talin1 cleavage and Itgav assembly, thereby compromising endothelial integrity and permeability. These findings identify potential therapeutic targets for TAD prevention and treatment. |
| format | Article |
| id | doaj-art-3641346b582249b9ac258bc5fa3eae65 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-3641346b582249b9ac258bc5fa3eae652025-08-20T03:15:35ZengWileyAdvanced Science2198-38442025-07-011225n/an/a10.1002/advs.202501112Calpain‐2‐Mediated Endothelial Focal Adhesion Disruption in Thoracic Aortic DissectionXiaomei Teng0Yansong Wang1Haoyue Huang2Yinglong Ding3Jun Wang4Meili Liu5Kun Song6Lianbo Shao7You Yu8Ziying Yang9Zhenya Shen10Department of Cardiovascular Surgery of the First Affiliated Hospital of Soochow University 899 Pinghai Road Suzhou 215006 ChinaInstitute for Cardiovascular Science Soochow University 178 Ganjiang Road Suzhou 215006 ChinaDepartment of Cardiovascular Surgery of the First Affiliated Hospital of Soochow University 899 Pinghai Road Suzhou 215006 ChinaDepartment of Cardiovascular Surgery of the First Affiliated Hospital of Soochow University 899 Pinghai Road Suzhou 215006 ChinaDepartment of Cardiovascular Surgery of the First Affiliated Hospital of Soochow University 899 Pinghai Road Suzhou 215006 ChinaDepartment of Cardiovascular Surgery of the First Affiliated Hospital of Soochow University 899 Pinghai Road Suzhou 215006 ChinaDepartment of Cardiovascular Surgery of the First Affiliated Hospital of Soochow University 899 Pinghai Road Suzhou 215006 ChinaDepartment of Cardiovascular Surgery of the First Affiliated Hospital of Soochow University 899 Pinghai Road Suzhou 215006 ChinaInstitute for Cardiovascular Science Soochow University 178 Ganjiang Road Suzhou 215006 ChinaDepartment of Cardiovascular Surgery of the First Affiliated Hospital of Soochow University 899 Pinghai Road Suzhou 215006 ChinaDepartment of Cardiovascular Surgery of the First Affiliated Hospital of Soochow University 899 Pinghai Road Suzhou 215006 ChinaAbstract Thoracic aortic dissection (TAD) is a life‐threatening condition with high mortality rates. Recent research suggests a potential link between early‐stage TAD and endothelial barrier dysfunction, although the underlying mechanisms remain unclear. Single‐cell RNA sequencing data from patients reveal that dysregulated Calpain‐2 expression modulates endothelial focal adhesion proteins, serving as an early pathological hallmark and driver of TAD. Elevated plasma calpain activity is strongly associated with an increased risk of TAD and organ dysfunction. Both endogenous and exogenous calpain inhibitors effectively prevent TAD onset and progression in murine models induced by β‐aminopropionitrile (BAPN). In early TAD, endothelial junction integrity in the ascending aorta and aortic arch is compromised. Endothelial‐specific deletion of Capns1 mitigates early and sustained endothelial focal adhesion damage by reducing aberrant expression of Integrin alpha‐V(Itgav), vinculin, and talin‐1, thereby decreasing TAD incidence. In contrast, macrophage‐specific Capns1 knockout does not impact TAD development but accelerates aortic dissection rupture in later stages. Mechanistically, angiotensin II upregulates Calpain‐2, leading to endothelial focal adhesion activation through talin1 cleavage and Itgav assembly, thereby compromising endothelial integrity and permeability. These findings identify potential therapeutic targets for TAD prevention and treatment.https://doi.org/10.1002/advs.202501112Calpain‐2focal adhesionItgavTalinthoracic aortic dissection |
| spellingShingle | Xiaomei Teng Yansong Wang Haoyue Huang Yinglong Ding Jun Wang Meili Liu Kun Song Lianbo Shao You Yu Ziying Yang Zhenya Shen Calpain‐2‐Mediated Endothelial Focal Adhesion Disruption in Thoracic Aortic Dissection Advanced Science Calpain‐2 focal adhesion Itgav Talin thoracic aortic dissection |
| title | Calpain‐2‐Mediated Endothelial Focal Adhesion Disruption in Thoracic Aortic Dissection |
| title_full | Calpain‐2‐Mediated Endothelial Focal Adhesion Disruption in Thoracic Aortic Dissection |
| title_fullStr | Calpain‐2‐Mediated Endothelial Focal Adhesion Disruption in Thoracic Aortic Dissection |
| title_full_unstemmed | Calpain‐2‐Mediated Endothelial Focal Adhesion Disruption in Thoracic Aortic Dissection |
| title_short | Calpain‐2‐Mediated Endothelial Focal Adhesion Disruption in Thoracic Aortic Dissection |
| title_sort | calpain 2 mediated endothelial focal adhesion disruption in thoracic aortic dissection |
| topic | Calpain‐2 focal adhesion Itgav Talin thoracic aortic dissection |
| url | https://doi.org/10.1002/advs.202501112 |
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