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

  • Cell Rep. 2022 Mar 8;38(10):110468. doi: 10.1016/j.celrep.2022.110468.
Jing Tan  1 ,  Ming Yang  1 ,  Haiping Wang  1 ,  Conghui Shen  1 ,  Maoxiong Wu  2 ,  He Xu  3 ,  Yandi Wu  1 ,  Yuanlong Li  1 ,  Xinghui Li  1 ,  Tongsheng Huang  1 ,  Shijie Deng  1 ,  Zhenyu Yang  1 ,  Saifei Gao  1 ,  Hui Li  1 ,  Jiaguo Zhou  4 ,  Hui Chen  5 ,  Nan Cao  6 ,  Weibin Cai  7
Affiliations
  • 1. Laboratory Animal Center and Department of Biochemistry, Institute of Guangdong Engineering and Technology Research Center for Disease-Model Animals, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
  • 2. Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
  • 3. Program of Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong 510080, China.
  • 4. Department of Pharmacology, Cardiac and Cerebrovascular Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong 510080, China.
  • 5. Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Electronic address: [email protected].
  • 6. Program of Stem Cells and Regenerative Medicine, Zhongshan School of Medicine, Sun Yat-Sen University, Guangdong 510080, China. Electronic address: [email protected].
  • 7. Laboratory Animal Center and Department of Biochemistry, Institute of Guangdong Engineering and Technology Research Center for Disease-Model Animals, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: [email protected].
PMID: 35263588 DOI: 10.1016/j.celrep.2022.110468
Abstract

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.

Keywords
cardiomyocyte proliferation; glucose oxidation; heart rate; heart regeneration; ivabradine; metabolic pattern; metoprolol; pentose phosphate pathway.
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