Posttranslational Modifications: Emerging Prospects for Cardiac Regeneration Therapy.

Heart failure (HF) following ischemic heart disease (IHD) remains a hard nut to crack and a leading cause of death worldwide. Cardiac regeneration aims to promote cardiomyocyte (CM) proliferation by transitioning the cell cycle state of CMs from arrest to re-entry. Protein posttranslational modifications (PTMs) have recently attracted extensive attention in the field of cardiac regeneration due to their reversibility and effects on the stability, activity, and subcellular localization of target proteins. The balance of PTMs is disrupted when neonatal CMs withdraw from the cell cycle, resulting in significant dysfunction of downstream substrate protein localization, expression, and activity, ultimately limiting the maintenance of cardiac regeneration ability. In this review, we summarize recent research concerning the role of PTMs in cardiac regeneration, while focusing on phosphorylation, acetylation, ubiquitination, glycosylation, methylation, and neddylation, and the effects of these modifications on CM proliferation, which may provide potential targets for future treatments for IHD.