Cardiovascular diseases (CVDs) are often linked to structural and functional impairments, such as heart defects and circulatory dysfunction, leading to compromised peripheral perfusion and heightened morbidity risks. Metabolic remodeling, particularly in the context of cardiac fibrosis and inflammation, is increasingly recognized as a pivotal factor in the pathogenesis of CVDs. Metabolic syndromes further predispose individuals to these conditions, underscoring the need to elucidate the metabolic underpinnings of CVDs. Lactate, a byproduct of glycolysis, is now recognized as a key molecule that connects cellular metabolism with the regulation of cellular activity. The transport of lactate between different cells is essential for metabolic homeostasis and signal transduction. Disruptions to lactate dynamics are implicated in various CVDs. Furthermore, lactylation, a novel post-translational modification, has been identified in cardiac cells, where it influences protein function and gene expression, thereby playing a significant role in CVD pathogenesis. In this review, we summarized recent advancements in understanding the role of lactate and lactylation in CVDs, offering fresh insights that could guide future research directions and therapeutic interventions. The potential of lactate metabolism and lactylation as innovative therapeutic targets for CVD is a promising avenue for exploration.
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http://dx.doi.org/10.1016/j.metabol.2024.155957 | DOI Listing |
J Inflamm Res
December 2024
Rheumatology Department, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, People's Republic of China.
Lactic acid (LA) is an essential glycolytic metabolite and energy source in the body, which is present in high levels in the synovial fluid of patients with rheumatoid arthritis (RA) and is a reliable indicator for identifying inflammatory arthritis. LA not only acts as an inflammatory amplifier in RA, recent studies have found that novel posttranslational modification (PTM) lactylation mediated by LA may also play a key role in RA. Single-cell sequencing showed that the RA lactylation score of patients with RA was significantly increased, and core lactylation-promoting genes, including NDUFB3, NGLY1, and other genes, were found to be potential biomarkers of RA.
View Article and Find Full Text PDFCell Death Differ
January 2025
Department of Hepatobiliary Surgery of the affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, China.
Lysine lactylation plays critical roles in various diseases, including cancer. Our previous study showed that lactylation of non-histone ABCF1 may be involved in hepatocellular carcinoma (HCC) progression. In this study, we evaluated the prognostic value of ABCF1-K430la in HCC using immunohistochemical staining and performed amino acid point mutations, multi-omics crossover, and biochemical experiments to investigate its biological role and underlying mechanism.
View Article and Find Full Text PDFNPJ Parkinsons Dis
January 2025
Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
The switch from oxidative phosphorylation to glycolysis is crucial for microglial activation. Recent studies highlight that histone lactylation promotes macrophage homeostatic gene expression via transcriptional regulation, but its role in microglia activation in Parkinson's disease (PD) remains unclear. Here, we demonstrated that inhibiting glycolysis with 2-deoxy-D-glucose alleviates microgliosis, neuroinflammation and dopaminergic neurons damage by reducing lactate accumulation in PD mice.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Growth, Development, and Mental Health of Children and Adolescence Center, Pediatric Research Institute, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, Chongqing Key Laboratory of Child Neurodevelopment and Cognitive Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.
Redox Biol
December 2024
China National Center for Bioinformation, Beijing, 100101, China; Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:
Lactate-mediated lactylation on target proteins is recently identified as the novel posttranslational modification with profound biological functions. RNA 5-methylcytosine (mC) modification possesses dynamic and reversible nature, suggesting that activity of its methyltransferase NSUN2 is actively regulated. However, how NSUN2 activity is response to acidic condition in tumor microenvironment and then regulates cancer cell survival remain to be clarified.
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