Work

Transcription factor ETV1 promotes angiogenesis after myocardial infarction via activation of the VEGFA/VEGFR2/eNOS pathway

Year: 2025

Type: article

Abstract: Background In 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. Methods In 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. Results The 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. Conclusions In 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.

Source: Frontiers in Cardiovascular Medicine

DOI: 10.3389/fcvm.2025.1633438

Authors: Jinyu Wang, Chunxia Li, Feng Li, Sen Fang, Yuan Chen

Institutions: Shanxi Medical University, Shanxi Academy of Medical Sciences, Tongji Hospital, Huazhong University of Science and Technology

Language: English

Topic: Angiogenesis and VEGF in Cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801