Liu Liu, Jiang Qiqi, Du Chong, Yang Tongtong, Zhou Liuhua, Chen Jiawen, Gu Lingfeng, Wang Qiming, Wang Zemu, Wang Hao, Wang Liansheng
Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
Eur J Pharmacol. 2024 Nov 15;983:177005. doi: 10.1016/j.ejphar.2024.177005. Epub 2024 Sep 19.
Restoration of the expression of factors regulating neonatal heart regeneration in the adult heart can promote myocardial repair. Therefore, investigations of the regulatory factors that play key roles in neonatal heart regeneration are urgently needed for the development of cardiac regenerative therapies. In our previous study, we identified ankyrin repeat domain 1 (Ankrd1) through multiomics analysis in a neonatal mouse model of cardiac regeneration and hypothesized that Ankrd1 plays a regulatory role in neonatal heart regeneration. In the present study, we aimed to determine the role of Ankrd1 in neonatal heart regeneration and adult myocardial repair. Our findings confirmed that Ankrd1 could mediate cardiomyocyte proliferation and that Ankrd1 knockdown in cardiomyocytes inhibited myocardial regeneration after apical resection in neonatal mice. Furthermore, we found that cardiomyocyte-specific Ankrd1 overexpression promoted cardiac repair and cardiac function recovery after adult myocardial infarction (MI). Mechanistically, Ankrd1 could regulate the cell cycle of cardiomyocytes and significantly mediate cardiac regeneration, at least in part, through cyclin D1. Overall, our study demonstrates that Ankrd1 is an effective target for achieving cardiac repair after MI, providing new ideas for the treatment of ischemic heart disease in the future.
恢复成年心脏中调节新生儿心脏再生的因子的表达可促进心肌修复。因此，为了开发心脏再生疗法，迫切需要对在新生儿心脏再生中起关键作用的调节因子进行研究。在我们之前的研究中，我们通过多组学分析在心脏再生的新生小鼠模型中鉴定出锚蛋白重复结构域1（Ankrd1），并假设Ankrd1在新生儿心脏再生中起调节作用。在本研究中，我们旨在确定Ankrd1在新生儿心脏再生和成年心肌修复中的作用。我们的研究结果证实，Ankrd1可介导心肌细胞增殖，并且在新生小鼠中，心肌细胞中Ankrd1的敲低会抑制心尖切除术后的心肌再生。此外，我们发现成年心肌梗死（MI）后，心肌细胞特异性过表达Ankrd1可促进心脏修复和心脏功能恢复。从机制上讲，Ankrd1可以调节心肌细胞的细胞周期，并且至少部分地通过细胞周期蛋白D1显著介导心脏再生。总体而言，我们的研究表明，Ankrd1是心肌梗死后实现心脏修复的有效靶点，为未来缺血性心脏病的治疗提供了新思路。
