Since myocardial infarction (MI) excessively damage the myocardium and blood vessels, the therapeutic approach for treating MI hearts should simultaneously target these two major components in the heart to achieve comprehensive cardiac repair. Here, we investigated a combinatory platform of ETV2 and Gata4, Mef2c and Tbx5 (GMT) transcription factors to develop a strategy that can rejuvenate both myocardium and vasculatures together in MI hearts. Previously ETV2 demonstrated significant effects on neovascularization and GMT was known to directly reprogram cardiac fibroblasts into cardiomyocytes under in vivo condition. Subsequently, intramyocardial delivery of a combination of retroviral GMT and adenoviral ETV2 particles into the rat MI hearts significantly increased viable myocardium area, capillary density compared to ETV2 or GMT only treated hearts, leading to improved heart function and reduced scar formation. These results demonstrate that this combinatorial gene therapy can be a promising approach to enhance the cardiac repair in MI hearts.

由于心肌梗死（MI）对心肌和血管造成过度损伤，因此治疗MI心脏的治疗方法应同时针对心脏中的这两种主要成分，以实现心脏的全面修复。在这里，我们研究了 ETV2 和 Gata4、Mef2c 和 Tbx5 (GMT) 转录因子的组合平台，以开发一种可以同时使 MI 心脏中的心肌和脉管系统恢复活力的策略。以前 ETV2 对新血管形成有显着影响，并且已知 GMT 在体内条件下直接将心脏成纤维细胞重编程为心肌细胞。随后，将逆转录病毒 GMT 和腺病毒 ETV2 颗粒组合的心肌内递送到大鼠 MI 心脏中显着增加了存活心肌面积，与仅处理 ETV2 或 GMT 的心脏相比，毛细血管密度可改善心脏功能并减少疤痕形成。这些结果表明，这种组合基因疗法可以成为增强心肌梗死心脏修复的有前途的方法。