| Autor: |
Yu F; National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore 169609, Singapore.; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.; Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore., Cong S; National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore 169609, Singapore.; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.; Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore., Yap EP; National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore 169609, Singapore.; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.; Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore., Hausenloy DJ; National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore 169609, Singapore.; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore 169857, Singapore.; Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore.; The Hatter Cardiovascular Institute, University College London, London WC1E 6HX, UK., Ramachandra CJ; National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore 169609, Singapore.; Cardiovascular & Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore 169857, Singapore. |
| Abstrakt: |
Ischemic heart disease (IHD) is the leading cause of heart failure (HF) and is a significant cause of morbidity and mortality globally. An ischemic event induces cardiomyocyte death, and the ability for the adult heart to repair itself is challenged by the limited proliferative capacity of resident cardiomyocytes. Intriguingly, changes in metabolic substrate utilisation at birth coincide with the terminal differentiation and reduced proliferation of cardiomyocytes, which argues for a role of cardiac metabolism in heart regeneration. As such, strategies aimed at modulating this metabolism-proliferation axis could, in theory, promote heart regeneration in the setting of IHD. However, the lack of mechanistic understanding of these cellular processes has made it challenging to develop therapeutic modalities that can effectively promote regeneration. Here, we review the role of metabolic substrates and mitochondria in heart regeneration, and discuss potential targets aimed at promoting cardiomyocyte cell cycle re-entry. While advances in cardiovascular therapies have reduced IHD-related deaths, this has resulted in a substantial increase in HF cases. A comprehensive understanding of the interplay between cardiac metabolism and heart regeneration could facilitate the discovery of novel therapeutic targets to repair the damaged heart and reduce risk of HF in patients with IHD. |
