Amino Acid Regulation in Metabolic Heart Disease: Mechanisms and Therapeutic Potential

In normal cardiac energy metabolism, 95% of the heart’s energy is provided by mitochondria, and preferences for energy-providing substrates vary at different times (Nguyen BY, Ruiz-Velasco A, Bui T, Collins L, Wang X, Liu W. Mitochondrial function in the heart: the insight into mechanisms and therapeutic potentials. Br J Pharmacol 2019;176(22):4302–4318). However, prolonged metabolic alterations impair cardiac function (Hu L, Tang D, Qi B, Guo D, Wang Y, Geng J, et al. Mfn2/Hsc70 complex mediates the formation of mitochondria-lipid droplets membrane contact and regulates myocardial lipid metabolism. Adv Sci (Weinh) 2024;11(14):e2307749). Therefore, this study primarily focuses on the relationship between amino acid metabolism and diabetic cardiomyopathy and atherosclerosis. Changes in metabolic processes also promote the development and worsening of these two diseases. Lipid and glucose metabolism in such diseases have been extensively studied, and emerging evidence suggests that amino acid metabolism also plays major roles in diabetic cardiomyopathy and atherosclerosis. Specific amino acid intake or catabolism might influence oxidative stress, inflammation, and fibrosis, among related processes, thus indirectly highlighting their potential as novel targets for metabolic interventions. However, the mechanisms and clinical relevance of amino acid metabolism in these diseases remain incompletely understood and warrant further investigation.