Transcription factor ETV1 promotes angiogenesis after myocardial infarction via activation of the VEGFA/VEGFR2/eNOS pathway
BackgroundIn our previous study, through integrative transcriptomic and ChIP-seq analysis, we revealed that ETV1 is a potential transcription factor involved in ventricular remodeling in the early stage of MI. This study aims to investigate the regulatory roles of ETV1 and whether ETV1 regulates ang...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2025.1633438/full |
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| author | Jinyu Wang Chunxia Li Feng Li Sen Fang Yuan Chen Yuan Chen |
| author_facet | Jinyu Wang Chunxia Li Feng Li Sen Fang Yuan Chen Yuan Chen |
| author_sort | Jinyu Wang |
| collection | DOAJ |
| description | BackgroundIn our previous study, through integrative transcriptomic and ChIP-seq analysis, we revealed that ETV1 is a potential transcription factor involved in ventricular remodeling in the early stage of MI. This study aims to investigate the regulatory roles of ETV1 and whether ETV1 regulates angiogenesis after MI.MethodsIn this study, MI model was induced by ligating the left anterior descending coronary artery. The expression of Etv1 was modulated via intramyocardial injection of adeno-associated virus serotype 9 (AAV9) with endothelial-specific promoter Icam2. Fibrosis was determined by Masson staining and apoptosis was assessed by TUNEL staining. Angiogenesis was evaluated by CD31 immunofluorescence staining. For in vitro experiments, HUVECs were transfected with ETV1 overexpression lentivirus, and wound healing and tube formation assays were performed to validate the angiogenic role of ETV1. Western blot was conducted to determine the level of angiogenetic factors and the underlying mechanisms.ResultsThe expression of Etv1 was decreased in the hearts of MI mice, as well as in isolated cardiac microvascular endothelial cells (CMECs). Moreover, overexpression of Etv1 alleviated the deterioration of heart function, mitigated the fibrosis, reduced apoptosis, and promoted angiogenesis after MI. Moreover, ETV1 overexpression enhanced migration and tube formation abilities of HUVECs. Mechanistically, ETV1 upregulated the expression of VEGFA, VEGFR2, and eNOS.ConclusionsIn summary, Etv1 promote angiogenesis via activating VEGFA/VEGFR2/eNOS pathway after MI, which further ameliorate adverse ventricular remodeling. These results suggest that ETV1 may serve as a potential target for the treatment of myocardial infarction. |
| format | Article |
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| institution | DOAJ |
| issn | 2297-055X |
| language | English |
| publishDate | 2025-08-01 |
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| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj-art-f160d359acea4e8887fc5dbd4b323efb2025-08-20T03:05:45ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-08-011210.3389/fcvm.2025.16334381633438Transcription factor ETV1 promotes angiogenesis after myocardial infarction via activation of the VEGFA/VEGFR2/eNOS pathwayJinyu Wang0Chunxia Li1Feng Li2Sen Fang3Yuan Chen4Yuan Chen5Department of Geriatric Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, ChinaDepartment of Geriatric Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, ChinaThird Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, ChinaThird Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, ChinaDepartment of Geriatric Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, ChinaDepartments of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaBackgroundIn our previous study, through integrative transcriptomic and ChIP-seq analysis, we revealed that ETV1 is a potential transcription factor involved in ventricular remodeling in the early stage of MI. This study aims to investigate the regulatory roles of ETV1 and whether ETV1 regulates angiogenesis after MI.MethodsIn this study, MI model was induced by ligating the left anterior descending coronary artery. The expression of Etv1 was modulated via intramyocardial injection of adeno-associated virus serotype 9 (AAV9) with endothelial-specific promoter Icam2. Fibrosis was determined by Masson staining and apoptosis was assessed by TUNEL staining. Angiogenesis was evaluated by CD31 immunofluorescence staining. For in vitro experiments, HUVECs were transfected with ETV1 overexpression lentivirus, and wound healing and tube formation assays were performed to validate the angiogenic role of ETV1. Western blot was conducted to determine the level of angiogenetic factors and the underlying mechanisms.ResultsThe expression of Etv1 was decreased in the hearts of MI mice, as well as in isolated cardiac microvascular endothelial cells (CMECs). Moreover, overexpression of Etv1 alleviated the deterioration of heart function, mitigated the fibrosis, reduced apoptosis, and promoted angiogenesis after MI. Moreover, ETV1 overexpression enhanced migration and tube formation abilities of HUVECs. Mechanistically, ETV1 upregulated the expression of VEGFA, VEGFR2, and eNOS.ConclusionsIn summary, Etv1 promote angiogenesis via activating VEGFA/VEGFR2/eNOS pathway after MI, which further ameliorate adverse ventricular remodeling. These results suggest that ETV1 may serve as a potential target for the treatment of myocardial infarction.https://www.frontiersin.org/articles/10.3389/fcvm.2025.1633438/fullmyocardial infarctionventricular remodelingETV1angiogenesisVEGF/VEGFR2/eNOS pathway |
| spellingShingle | Jinyu Wang Chunxia Li Feng Li Sen Fang Yuan Chen Yuan Chen Transcription factor ETV1 promotes angiogenesis after myocardial infarction via activation of the VEGFA/VEGFR2/eNOS pathway Frontiers in Cardiovascular Medicine myocardial infarction ventricular remodeling ETV1 angiogenesis VEGF/VEGFR2/eNOS pathway |
| title | Transcription factor ETV1 promotes angiogenesis after myocardial infarction via activation of the VEGFA/VEGFR2/eNOS pathway |
| title_full | Transcription factor ETV1 promotes angiogenesis after myocardial infarction via activation of the VEGFA/VEGFR2/eNOS pathway |
| title_fullStr | Transcription factor ETV1 promotes angiogenesis after myocardial infarction via activation of the VEGFA/VEGFR2/eNOS pathway |
| title_full_unstemmed | Transcription factor ETV1 promotes angiogenesis after myocardial infarction via activation of the VEGFA/VEGFR2/eNOS pathway |
| title_short | Transcription factor ETV1 promotes angiogenesis after myocardial infarction via activation of the VEGFA/VEGFR2/eNOS pathway |
| title_sort | transcription factor etv1 promotes angiogenesis after myocardial infarction via activation of the vegfa vegfr2 enos pathway |
| topic | myocardial infarction ventricular remodeling ETV1 angiogenesis VEGF/VEGFR2/eNOS pathway |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2025.1633438/full |
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