The Role of Glucose Metabolic Reprogramming in Myocard itis and Advances in Therapeutic Strategies

Abstract

Myocarditis is a heterogeneous inflammatory heart disease most co mmonly triggered by viral infections, such as Coxsackievirus B3 (C VB3), and may progress to dilated cardiomyopathy (DCM) and hear t failure. Growing evidence indicates that glucose metabolic reprogr amming in cardiomyocytes and infiltrating immune cells plays a piv otal role in the initiation and progression of myocarditis. Under phy siological conditions, the adult heart primarily relies on fatty acid β-oxidation for energy production, whereas glucose oxidation serve s a supplementary role. In contrast, myocarditis is characterized by a metabolic shift from oxidative phosphorylation toward enhanced a erobic glycolysis, known as the Warburg effect. This shift results in reduced ATP efficiency, lactate accumulation, excessive reactive ox ygen species production, and amplification of inflammatory response s, thereby establishing a self-sustaining immunometabolic vicious cy cle. This review summarizes glucose metabolism in the normal heart an d highlights the features and regulatory mechanisms of glucose met abolic reprogramming in myocarditis, including the HIF-1α/mTOR axis, NRF2-mediated pentose phosphate pathway, IRG1/itaconate axi s, and PGK1. We also discuss emerging therapeutic strategies target ing glucose metabolism, as well as current challenges in clinical tra nslation. Advances in multi-omics technologies may facilitate the de velopment of precise metabolic interventions for myocarditis.