Lina Xuan, Guangze Wang, Xiufang Li, Shengjie Wang, Yuman Gao, Jingheng Wang, Hui Zhang, Shuo Zhuang, Huishan Luo, Jianjun Guo, Mingyu Zhang, Xingmei Yang, Hailong Zhang, Qingqing Zhang, Yiyang Qiao, Kai Kang, Ying Zhang, Lihua Sun
Myocardial infarction (MI) remains the leading cause of death due to cardiovascular disease worldwide. role of MYZAP in angiogenesis remains unclear. The expression of MYZAP in MI was significantly decreased. Endothelial-specific overexpression of MYZAP improved cardiac function, increased angiogenesis, and restored hindlimb blood flow levels in MI mice detected by MoorFLPIReview. The proliferation ability, migration, and invasion of endothelial cells were reduced after hypoxia, which were restored after overexpression of MYZAP or knockdown of RND1. The pro-angiogenic effect of MYZAP overexpression was reversed by RND1 overexpression. The proliferation ability, migration and invasion ability, and tube formation ability of endothelial cells were significantly reduced after knockdown of MYZAP. Direct interaction between MYZAP and RND1 was confirmed by co-immunoprecipitation (Co-IP) and thermal stability assays. TRIM21 was identified as a potential E3 ubiquitin ligase responsible for RND1 degradation. Our work revealed that endothelial-specific overexpression of MYZAP enhances angiogenesis by activating the VEGF/PI3K/AKT pathway in MI.