Moderate heart rate reduction promotes cardiac regeneration through stimulation of the metabolic pattern switch

• Published in: Cell reports (Cambridge) 2022-03, Vol.38 (10), p.110468-110468, Article 110468
• Main Authors: Tan, Jing, Yang, Ming, Wang, Haiping, Shen, Conghui, Wu, Maoxiong, Xu, He, Wu, Yandi, Li, Yuanlong, Li, Xinghui, Huang, Tongsheng, Deng, Shijie, Yang, Zhenyu, Gao, Saifei, Li, Hui, Zhou, Jiaguo, Chen, Hui, Cao, Nan, Cai, Weibin
• Format: Article
• Language: English
• Subjects: Bradycardia - metabolism; cardiomyocyte proliferation; Energy Metabolism; glucose oxidation; Heart; Heart Rate; heart regeneration; Humans; ivabradine; metabolic pattern; metoprolol; Myocardium - metabolism; Myocytes, Cardiac - metabolism; pentose phosphate pathway
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2022.110468

As a biological pump, the heart needs to consume a substantial amount of energy to maintain sustained beating. Myocardial energy metabolism was recently reported to be related to the loss of proliferative capacity in cardiomyocytes (CMs). However, the intrinsic relationship between beating rate and proliferation in CMs and whether energy metabolism can regulate this relationship remains unclear. In this study, we find that moderate heart rate reduction (HRR) induces CM proliferation under physiological conditions and promotes cardiac regenerative repair after myocardial injury. Mechanistically, moderate HRR induces G1/S transition and increases the expression of glycolytic enzymes in CMs. Furthermore, moderate HRR induces a metabolic pattern switch, activating glucose metabolism and increasing the relative proportion of ATP production by the glycolytic pathway for biosynthesis of substrates needed for proliferative CMs. These results highlight the potential therapeutic role of HRR in not only acute myocardial protection but also long-term CM restoration. [Display omitted] •Moderate heart rate reduction promotes CM proliferation and heart regeneration•Heart rate reduction upregulates metabolic enzymes to induce CM cell cycle re-entry•Heart rate reduction activates PPP and biosynthetic metabolism for CM proliferation Tan et al. demonstrate that moderate heart rate reduction (HRR) stimulates a metabolic pattern switch to induce cardiomyocyte (CM) proliferation under physiological conditions and promotes cardiac regenerative repair after myocardial injury. These results highlight the potential therapeutic role of HRR in acute myocardial protection and long-term CM restoration.