The role of lactate in cardiovascular diseases

Figures

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  Fig. 1. Schematic diagram of the lactate shuttle. In the cytoplasm, lactate is transformed into pyruvic acid under the catalysis of LDHB and then enters the mitochondrial tricarboxylic acid cycle (TAC). In addition, lactate can enter the mitochondria directly through the lactate oxidation complex (LOC) on the inner mitochondrial membrane and be converted into pyruvic acid. Lactate is also the precursor of gluconeogenesis. Lactate can be used as a substrate for posttranslational modification (PTM), causing the lactylation of histones and nonhistones, and can then regulate gene expression or protein function. Abbreviations: TAC: tricarboxylic acid cycle; PTM: posttranslational modification; LOC: lactate oxidation complex; PKM2: M2-type pyruvate kinase; AK2: adenylate kinase 2

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  Fig. 2. Schematic diagram of the physiological function of metabolites in the glycolysis pathway. A variety of metabolites produced during glycolysis have very important physiological functions. For example, glucose-6-phosphate is the precursor of gluconeogenesis, and it can enter the pentose phosphate pathway; fructose 1,6-bisphosphate can inhibit osteoclastogenesis; glyceraldehyde phosphate can promote the production of FGF23 by bone; phosphoenolpyruvate can inhibit the differentiation of TH17 cells and regulate the autoimmune system; and lactate can promote the development of the cerebral neocortex. Abbreviations: FGF23: fibroblast growth factor 23; HK2: hexokinase; PFK1: phosphofructokinase-1; PDH: pyruvate dehydrogenase; TAC: tricarboxylic acid cycle; LDH: lactate dehydrogenase

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  Fig. 3. Schematic diagram of the role of lactate in heart failure, myocardial infarction, atrial fibrillation and atherosclerosis. In heart failure, the increase in lactate levels in myocardial cells can improve myocardial metabolism through the pyruvate-lactate axis, thereby improving myocardial hypertrophy. In addition, recent studies have found that α-MHC-K1897la lactylation can improve sarcomeric structure and function, thereby alleviating the development of heart failure. Furthermore, lactate can regulate the production of inflammatory cytokines by myocardial fibroblasts, reducing the production of Fas, Fraktalkine, or IL-12p40 and stimulating IL-13 and SDF1a to improve heart failure. It is unclear whether lactylation in myocardial fibroblasts involve in heart failure. In myocardial infarction, the early increase in the level of H3K18la in monocytes can promote the expression of repair genes (Lrg1, Vegf-α, and IL-10), thereby improving myocardial infarction. In addition, in the later stage, the increase in snail1 lactylation in vascular endothelial cells can promote the expression of tfg genes, thereby promoting the occurrence of EndMT and exacerbating the occurrence of myocardial…