The role of glucose metabolic reprogramming in myocarditis and advances in therapeutic strategies

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  Figure 1. Cellular interactions and immunometabolic mechanisms in myocarditis. Viral infection (e.g., Coxsackievirus B3 and Parvovirus B19) or immune dysregulation directly injures cardiomyocytes, leading to mitochondrial dysfunction and a metabolic shift from oxidative phosphorylation toward glycolysis. Enhanced glycolysis is accompanied by lactate and reactive oxygen species (ROS) accumulation, promoting cardiomyocyte death, including apoptosis and ferroptosis, as well as the release of damage-associated molecular patterns (DAMPs). The inflammatory microenvironment subsequently recruits and activates immune cells. Pro-inflammatory macrophages (M1) and effector T cells (Th1/Th17) rely on glycolysis to sustain inflammatory functions and secrete pro-inflammatory cytokines, thereby exacerbating myocardial injury. In contrast, anti-inflammatory macrophages (M2) and regulatory T cells (Treg) preferentially utilize oxidative phosphorylation and fatty acid oxidation, contributing to inflammation resolution and tissue repair. Neutrophils rapidly infiltrate the heart during the acute phase and amplify inflammation through glycolysis-dependent ROS release and neutrophil extracellular trap…

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  Figure 2. Schematic overview of glucose metabolic reprogramming in myocarditis. Viral infection or immune dysregulation induces mitochondrial dysfunction in cardiomyocytes, leading to a metabolic shift from oxidative phosphorylation toward glycolysis. Enhanced glycolysis is accompanied by lactate accumulation and activation of alternative metabolic pathways, resulting in increased reactive oxygen species production and amplification of inflammatory responses. The reciprocal interaction between metabolic abnormalities and immune cell activation establishes a self-sustaining immunometabolic feedback loop, which becomes pathologically fixed over time and ultimately drives myocardial injury, fibrosis, and cardiac dysfunction.