Wang Jinyu, Li Chunxia, Li Feng, Fang Sen, Chen Yuan
Department of Geriatric Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, China.
Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China.
Front Cardiovasc Med. 2025 Aug 15;12:1633438. doi: 10.3389/fcvm.2025.1633438. eCollection 2025.
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.
In this study, MI model was induced by ligating the left anterior descending coronary artery. The expression of was modulated via intramyocardial injection of adeno-associated virus serotype 9 (AAV9) with endothelial-specific promoter . Fibrosis was determined by Masson staining and apoptosis was assessed by TUNEL staining. Angiogenesis was evaluated by CD31 immunofluorescence staining. For experiments, HUVECs were transfected with overexpression lentivirus, and wound healing and tube formation assays were performed to validate the angiogenic role of . Western blot was conducted to determine the level of angiogenetic factors and the underlying mechanisms.
The expression of was decreased in the hearts of MI mice, as well as in isolated cardiac microvascular endothelial cells (CMECs). Moreover, overexpression of alleviated the deterioration of heart function, mitigated the fibrosis, reduced apoptosis, and promoted angiogenesis after MI. Moreover, overexpression enhanced migration and tube formation abilities of HUVECs. Mechanistically, ETV1 upregulated the expression of VEGFA, VEGFR2, and eNOS.
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.
在我们之前的研究中，通过整合转录组学和ChIP-seq分析，我们揭示了ETV1是心肌梗死早期参与心室重塑的潜在转录因子。本研究旨在探讨ETV1的调节作用以及ETV1是否在心肌梗死后调节血管生成。
在本研究中，通过结扎左冠状动脉前降支诱导心肌梗死模型。通过心肌内注射具有内皮特异性启动子的9型腺相关病毒（AAV9）来调节 的表达。通过Masson染色确定纤维化，并通过TUNEL染色评估细胞凋亡。通过CD31免疫荧光染色评估血管生成。对于 实验，用 过表达慢病毒转染人脐静脉内皮细胞（HUVECs），并进行伤口愈合和管形成试验以验证 的血管生成作用。进行蛋白质免疫印迹以确定血管生成因子的水平及其潜在机制。
ETV1在心肌梗死小鼠心脏以及分离的心脏微血管内皮细胞（CMECs）中的表达降低。此外，ETV1过表达减轻了心肌梗死后心脏功能的恶化，减轻了纤维化，减少了细胞凋亡，并促进了血管生成。此外，ETV1过表达增强了HUVECs的迁移和管形成能力。机制上，ETV1上调了VEGFA、VEGFR2和eNOS的表达。
总之，Etv1在心肌梗死后通过激活VEGFA/VEGFR2/eNOS途径促进血管生成，进而改善不良心室重塑。这些结果表明ETV1可能作为心肌梗死治疗的潜在靶点。
