Sirt4 Deficiency Promotes Cardiomyocyte Proliferation and Cardiac Repair

作者：Weijing Liu, Jie Feng, Yuan Zhang, Yanyan Hao, Jiajun Zhong, Xinchang Liu, Dongcheng Cai, Hao Liu, Lina Bai, Miaoqing Hu, Hong Lian, Yu Nie, Hou‐Zao Chen, Yuyao Wang · 发表于：Journal of Cellular and Molecular Medicine · 年份：2025 · DOI：10.1111/jcmm.70741 · 被引用次数：5 · 研究领域：Sirtuins and Resveratrol in Medicine、Cardiac Ischemia and Reperfusion、Cardiovascular Effects of Exercise

The mammalian heart exhibits transient but remarkable regenerative capacity during the early postnatal period, after which most cardiomyocytes exit the cell cycle. While the sirtuin family is well-established as regulators of cell cycle progression, its specific role in cardiomyocyte proliferation and cardiac regeneration remains unclear. In this study, we found that Sirt4 expression increased during postnatal heart development. Adenovirus-mediated Sirt4 overexpression in vitro inhibited cardiomyocyte proliferation by inducing oxidative DNA damage. Moreover, cardiomyocyte-specific Sirt4 overexpression in vivo suppressed cardiomyocyte proliferation and impaired neonatal heart regeneration. Using Sirt4-knockout mice, we found that Sirt4 deficiency promoted cardiomyocyte proliferation and extended the heart regeneration window. Furthermore, Sirt4 deficiency improved cardiac function and reduced myocardial fibrosis after ischaemia-reperfusion injury in adult mice. These findings establish Sirt4 as a critical regulator of cardiomyocyte proliferation and cardiac repair, suggesting that targeted Sirt4 inhibition may represent a promising therapeutic strategy for ischaemic heart diseases.