Altered Acylcarnitine Metabolism in cardiac diseases: From molecular mechanisms to translational potential

Cardiovascular diseases (CVDs) are a leading global cause of mortality and disease burden, closely associated with the remodeling of myocardial energy metabolism. Acylcarnitines (Acs) are key intermediates in the carnitine shuttle and fatty acid β-oxidation (FAO) processes. They play a critical role in transporting long-chain fatty acids across the mitochondrial membrane, maintaining the intracellular acyl-CoA/CoA balance, and buffering metabolic flux. Recent metabolomics studies have demonstrated significant abnormalities in acylcarnitine profiles across various cardiac diseases, including coronary artery disease, ischemia-reperfusion injury, heart failure, diabetic cardiomyopathy, and arrhythmias. These abnormalities are closely correlated with disease severity, metabolic disturbances, and poor clinical prognosis. Mechanistically, the pathological accumulation of long-chain acylcarnitines triggers lipotoxicity, exacerbates mitochondrial oxidative stress, and impairs calcium homeostasis, which collectively drive inflammation and cardiomyocyte apoptosis. This review systematically summarizes the physiological roles of the carnitine shuttle, explores the underlying mechanisms of acylcarnitine-induced cardiac injury, and highlights their translational potential as promising diagnostic biomarkers and novel therapeutic targets for cardiovascular metabolic interventions.