Metabolic Regulation of Cardiac Regeneration

Abstract

The mortality due to heart diseases remains highest in the world every year, with ischemic cardiomyopathy being the prime cause. The irreversible loss of cardiomyocytes following myocardial injury leads to compromised contractility of the remaining myocardium, adverse cardiac remodeling, and ultimately heart failure. The hearts of adult mammals can hardly regenerate after cardiac injury since adult cardiomyocytes exit the cell cycle. Nonetheless, the hearts of early neonatal mammals possess a stronger capacity for regeneration. To improve the prognosis of patients with heart failure and to find the effective therapeutic strategies for it, it is essential to promote endogenous regeneration of adult mammalian cardiomyocytes. Mitochondrial metabolism maintains normal physiological functions of the heart and compensates for heart failure. In recent decades, the focus is on the changes in myocardial energy metabolism, including glucose, fatty acid, and amino acid metabolism, in cardiac physiological and pathological states. In addition to being a source of energy, metabolites are becoming key regulators of gene expression and epigenetic patterns, which may affect heart regeneration. However, the myocardial energy metabolism during heart regeneration is majorly unknown. This review focuses on the role of energy metabolism in cardiac regeneration, intending to shed light on the strategies for manipulating heart regeneration and promoting heart repair after cardiac injury.

Checkpoint Kinase 1 Stimulates Endogenous Cardiomyocyte Renewal and Cardiac Repair by Binding to Pyruvate Kinase Isoform M2 C‐Domain and Activating Cardiac Metabolic Reprogramming in a Porcine Model of Myocardial Ischemia/Reperfusion Injury

“…Previous studies found that the transition from glycolysis to fatty acid metabolism in postnatal hearts is consistent with the loss of cardiac regenerative capacity. 25 , 26 Furthermore, the activation of PKM2 was found to promote the G6PD‐dependent pentose phosphate pathway and stimulate cardiomyocyte proliferation after MI. 27 Because PKM2 and G6PD were not activated in the I/R+hydrogel group, the mechanism experiments were mainly conducted in the I/R+hydrogel group and I/R+rhCHK1‐hydrogel group, and relevant data were analyzed in these 2 groups.…”

Tg(Δ113p53:cmyc) Transgene Upregulates glut1 Expression to Promote Zebrafish Heart Regeneration

“…Developmental change and injury response of the heart lead to a metabolic shift to glycolysis for energy production [ 28 ]. Cancer cells have a higher capacity of proliferation and there exists a Warburg effect.…”

Engineering Spatiotemporal Control in Vascularized Tissues

“…Cardiovascular disease (CVD) remains a major cause of morbidity and mortality all over the world, causing approximately 17.9 million deaths per year in the United States [ 1 ]. Heart failure, the inability of heart to provide sufficient blood flow to the body, is largely attributed to the non-regenerative cardiomyocytes that provide contractility to the heart [ 2 ]. Myocardial injury results in cardiac remodeling and adverse fibrosis, resulting in fibrotic scar tissue [ 3 ].…”