AREG+ regulatory T cells mediating myocardial repair and neovascularization after myocardial infarction
Abstract Enhancing tissue repair and angiogenesis post-Acute myocardial infarction (AMI) is critical to improving cardiac function and preventing heart failure. Recent studies have highlighted the interaction between immune cells and endothelial cells in post-AMI angiogenesis, yet the specific contr...
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2025-06-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-025-01281-8 |
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| author | Yan Wang Jiao Li Yu Zhang Pingping He Weiwei Liu Weirong Zeng Chaofu Li Yixuan Gao Yongchao Zhao Changyin Shen Wenming Chen Yunhang Li Ranzun Zhao Bei Shi |
| author_facet | Yan Wang Jiao Li Yu Zhang Pingping He Weiwei Liu Weirong Zeng Chaofu Li Yixuan Gao Yongchao Zhao Changyin Shen Wenming Chen Yunhang Li Ranzun Zhao Bei Shi |
| author_sort | Yan Wang |
| collection | DOAJ |
| description | Abstract Enhancing tissue repair and angiogenesis post-Acute myocardial infarction (AMI) is critical to improving cardiac function and preventing heart failure. Recent studies have highlighted the interaction between immune cells and endothelial cells in post-AMI angiogenesis, yet the specific contributions of different immune cell subsets remain poorly understood. Emerging evidence suggests the presence of a subset of regulatory T cells (Tregs) expressing Amphiregulin (AREG) in infarcted myocardial tissue, with AREG acting as a paracrine protein that plays a key role in angiogenesis. However, whether AREG⁺ Tregs mediate post-AMI angiogenesis and the underlying molecular mechanisms remain unclear. In this study, we demonstrate that Treg activation promotes tissue repair and improves cardiac function after AMI, although it does not significantly impact angiogenesis or endothelial cell behaviors. Notably, overexpression of AREG⁺ Tregs stimulates robust neovascularization post-AMI, reduces myocardial fibrosis, and further enhances cardiac function. Our in vitro data reveal that AREG⁺ Tregs secrete not only AREG but also angiogenic factors such as VEGF and FGF, which promote endothelial cell proliferation, migration, and tube formation. RNA sequencing analysis identifies FoxM1 as a key regulator of this angiogenic process in cardiac microvascular endothelial cells (CMECs). Importantly, inhibition of AREG in Tregs abolishes the FoxM1-dependent angiogenic response.In summary, we identified AREG⁺ Tregs as a distinct cell population driving neovascularization post-AMI, with FoxM1-mediated angiogenesis in CMECs. This may provide a foundation for harnessing specific Treg subsets for cardioprotection following AMI. |
| format | Article |
| id | doaj-art-1a7ae6fe2ceb4178b8ca787642de93d2 |
| institution | DOAJ |
| issn | 1528-3658 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj-art-1a7ae6fe2ceb4178b8ca787642de93d22025-08-20T02:39:24ZengBMCMolecular Medicine1528-36582025-06-0131111810.1186/s10020-025-01281-8AREG+ regulatory T cells mediating myocardial repair and neovascularization after myocardial infarctionYan Wang0Jiao Li1Yu Zhang2Pingping He3Weiwei Liu4Weirong Zeng5Chaofu Li6Yixuan Gao7Yongchao Zhao8Changyin Shen9Wenming Chen10Yunhang Li11Ranzun Zhao12Bei Shi13Department of Cardiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiology, Guizhou Provincial Staff HospitalDepartment of Cardiology, Affiliated Hospital of Zunyi Medical UniversityDepartment of Cardiology, Affiliated Hospital of Zunyi Medical UniversityAbstract Enhancing tissue repair and angiogenesis post-Acute myocardial infarction (AMI) is critical to improving cardiac function and preventing heart failure. Recent studies have highlighted the interaction between immune cells and endothelial cells in post-AMI angiogenesis, yet the specific contributions of different immune cell subsets remain poorly understood. Emerging evidence suggests the presence of a subset of regulatory T cells (Tregs) expressing Amphiregulin (AREG) in infarcted myocardial tissue, with AREG acting as a paracrine protein that plays a key role in angiogenesis. However, whether AREG⁺ Tregs mediate post-AMI angiogenesis and the underlying molecular mechanisms remain unclear. In this study, we demonstrate that Treg activation promotes tissue repair and improves cardiac function after AMI, although it does not significantly impact angiogenesis or endothelial cell behaviors. Notably, overexpression of AREG⁺ Tregs stimulates robust neovascularization post-AMI, reduces myocardial fibrosis, and further enhances cardiac function. Our in vitro data reveal that AREG⁺ Tregs secrete not only AREG but also angiogenic factors such as VEGF and FGF, which promote endothelial cell proliferation, migration, and tube formation. RNA sequencing analysis identifies FoxM1 as a key regulator of this angiogenic process in cardiac microvascular endothelial cells (CMECs). Importantly, inhibition of AREG in Tregs abolishes the FoxM1-dependent angiogenic response.In summary, we identified AREG⁺ Tregs as a distinct cell population driving neovascularization post-AMI, with FoxM1-mediated angiogenesis in CMECs. This may provide a foundation for harnessing specific Treg subsets for cardioprotection following AMI.https://doi.org/10.1186/s10020-025-01281-8Acute myocardial infarctionNeovascularizationAREGRegulatory T cellsFoxM1 |
| spellingShingle | Yan Wang Jiao Li Yu Zhang Pingping He Weiwei Liu Weirong Zeng Chaofu Li Yixuan Gao Yongchao Zhao Changyin Shen Wenming Chen Yunhang Li Ranzun Zhao Bei Shi AREG+ regulatory T cells mediating myocardial repair and neovascularization after myocardial infarction Molecular Medicine Acute myocardial infarction Neovascularization AREG Regulatory T cells FoxM1 |
| title | AREG+ regulatory T cells mediating myocardial repair and neovascularization after myocardial infarction |
| title_full | AREG+ regulatory T cells mediating myocardial repair and neovascularization after myocardial infarction |
| title_fullStr | AREG+ regulatory T cells mediating myocardial repair and neovascularization after myocardial infarction |
| title_full_unstemmed | AREG+ regulatory T cells mediating myocardial repair and neovascularization after myocardial infarction |
| title_short | AREG+ regulatory T cells mediating myocardial repair and neovascularization after myocardial infarction |
| title_sort | areg regulatory t cells mediating myocardial repair and neovascularization after myocardial infarction |
| topic | Acute myocardial infarction Neovascularization AREG Regulatory T cells FoxM1 |
| url | https://doi.org/10.1186/s10020-025-01281-8 |
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