Lactate-induced lactylation and cardiometabolic diseases: From epigenetic regulation to therapeutics

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер 1870(6), С. 167247 - 167247

Опубликована: Май 16, 2024

Язык: Английский

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Regulation of macrophage activation by lactylation in lung disease

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Июль 4, 2024

Lactylation is a process where lactate, cellular metabolism byproduct, added to proteins, altering their functions. In the realm of macrophage activation, lactylation impacts inflammatory response and immune regulation. Understanding effects on activation vital in lung diseases, as abnormal function are pivotal conditions like pneumonia, pulmonary fibrosis, COPD, cancer. This review explores concept lactylation, its regulation recent research progress diseases. It offers new insights into disease pathogenesis potential therapeutic targets.

Язык: Английский

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Pulmonary Hypertension: Molecular Mechanisms and Clinical Studies

MedComm, Год журнала: 2025, Номер 6(3)

Опубликована: Март 1, 2025

Pulmonary hypertension (PH) stands as a tumor paradigm cardiovascular disease marked by hyperproliferation of cells and vascular remodeling, culminating in heart failure. Complex genetic epigenetic mechanisms collectively contribute to the disruption pulmonary homeostasis. In recent years, advancements research technology have identified numerous gene deletions mutations, addition bone morphogenetic protein receptor type 2, that are closely associated with remodeling process PH. Additionally, modifications such RNA methylation, DNA histone modification, noncoding RNAs been shown precisely regulate PH molecular networks cell-type-specific manner, emerging potential biomarkers therapeutic targets. This review summarizes analyzes roles currently genes factors PH, emphasizing pivotal role long ncRNAs its regulation. it examines current clinical preclinical therapies for targeting these explores new treatment strategies.

Язык: Английский

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Lactate dehydrogenase A (LDHA)-mediated lactate generation promotes pulmonary vascular remodeling in pulmonary hypertension

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Авг. 5, 2024

High levels of lactate are positively associated with prognosis and mortality in pulmonary hypertension (PH). Lactate dehydrogenase A (LDHA) is a key enzyme for the production lactate. This study undertaken to investigate role molecular mechanisms LDHA PH.

Язык: Английский

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Single-cell characterization of the immune heterogeneity of pulmonary hypertension identifies novel targets for immunotherapy

BMC Immunology, Год журнала: 2025, Номер 26(1)

Опубликована: Фев. 10, 2025

Pulmonary arterial hypertension (PAH) is a critical cardiopulmonary vascular disorder marked by the progressive elevation of pulmonary artery pressure, increased resistance, and eventual right heart failure. Research has shown that various immune cells play significant role in pathogenesis PAH, both patients diagnosed with condition experimental models PAH. Cell–cell communication important for PAH progression therapies, while global cell landscape intercellular signaling not been elucidated. We performed single-cell RNA sequencing on NCBI Gene Expression Omnibus (GEO) databases GSE169471, GSE 210248, GSE228643 GSE244781, analyzed lung tissue samples across healthy controls patients. In total, approximately 124,561 were total 34 clusters identified. integrated results multiple used an enhanced workflow to overcome limitations single study. this study, we elucidated functional characteristics potential regulatory interactions several subpopulations have previously documented similar research. constructed comprehensive communications at resolution, which expected significantly advance development personalized diagnostic therapeutic strategies demonstrated transcriptomic features different types presented in-depth analysis T subsets, myeloid heterogeneity SMCs FBs subsets dynamics exhibited suggests targeting cytotoxic regulation may be strategy. Significant changes functions especially focused GPNMB+ macrophages. addition, CellChat NicheNet analyses reveal altered dys-regulated pathways progression. The MIF IL-1 induced inflammatory response greatly driven. systematically explored population target valuable developing new precise therapies.

Язык: Английский

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The role of lactate metabolism and lactylation in pulmonary arterial hypertension

Respiratory Research, Год журнала: 2025, Номер 26(1)

Опубликована: Март 12, 2025

Pulmonary arterial hypertension (PAH) is a complex and progressive disease characterized by elevated pulmonary artery pressure vascular remodeling. Recent studies have underscored the pivotal role of metabolic dysregulation epigenetic modifications in pathogenesis PAH. Lactate, byproduct glycolysis, now recognized as key molecule that links cellular metabolism with activity regulation. findings indicate that, addition to altered glycolytic dysregulated. Lactate homeostasis lactylation—a novel modification—also play significant development This review synthesizes current knowledge regarding relationship between PAH, particular focus on cumulative effects lactate cells. Furthermore, lactylation, an emerging modification, discussed context By elucidating interplay lactylation this aims provide insights into potential therapeutic targets. Understanding these pathways may lead innovative strategies for managing PAH improving patient outcomes. Future research should underlying mechanisms through which influences pathophysiology thereby aiding targeted interventions.

Язык: Английский

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Turning sour into sweet: Lactylation modification as a promising target in cardiovascular health

Metabolism, Год журнала: 2025, Номер unknown, С. 156234 - 156234

Опубликована: Март 1, 2025

Язык: Английский

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Heterogeneity of Neutrophils and Immunological Function in Neonatal Sepsis: Analysis of Molecular Subtypes Based on Hypoxia–Glycolysis–Lactylation

Mediators of Inflammation, Год журнала: 2025, Номер 2025(1)

Опубликована: Янв. 1, 2025

Objective: Hypoxia-glycolysis-lactylation (HGL) may play a crucial role in neonatal sepsis (NS). This study aims to identify HGL marker genes NS and explore immune microenvironment among subtypes. Materials Methods: The gene expression dataset GSE69686, comprising 64 cases 85 controls, was selected for analysis. Based on the screened HGL-related genes, diagnostic prediction models were constructed using nine machine learning algorithms, molecular subtypes of identified through consensus clustering. Subsequently, heterogeneity biological functions cell infiltration different analyzed. Finally, lactylation validated GSE25504 dataset, clinical samples, mouse neutrophil, respectively. Results: MERTK, HK3, PGK1, STAT3 as model support vector (SVM) algorithm exhibited optimal predictive performance. patterns, two distinct identified. Functional enrichment analysis highlighted significant immune-related pathways, while revealed differences neutrophil proportions between Furthermore, levels positively correlated with infiltration. Importantly, experimental validation results consistent findings from bioinformatics Conclusion: their associated genes. These will contribute elucidating disease's establishing appropriate personalized therapeutic approaches.

Язык: Английский

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Machine learning algorithms integrate bulk and single-cell RNA data to reveal the crosstalk and heterogeneity of Glycolysis and Lactylation activity following Pulmonary Arterial Hypertension

Research Square (Research Square), Год журнала: 2025, Номер unknown

Опубликована: Апрель 25, 2025

Background: Glycolysis and lactylation activity significantly impact the pathogenesis of Pulmonary Arterial Hypertension (PAH); however, studies exploring their heterogeneity potential correlation at single-cell level are still lacking. Identifying feature genes that commonly regulated by both glycolysis could enhance our understanding PAH. Methods: We employed RNA sequencing (scRNA-seq) to investigate across various cellular tiers following PAH, aiming acquire comprehensive biological insights into We Utilized AUCell, Ucell, singscore, ssGSEA, AddModuleScore algorithms identify common positive negative in PAH level. Furthermore, we three machine learning algorithms, Boruta, Random Forest, SVM-RFE optimal related BulkRNA-seq further leveraged CellChat pseudotime analysis delve regulatory mechanisms characteristic genes. used qPCR detect expression ACTR2, CCDC88A, MRC1 rat model pulmonary hypertension. Results: For first time level, discovered activities exhibit different cell layers However, show remarkable consistency, being highly active macrophages, fibroblasts, monocytes, epithelial cells, while displaying lower lymphatic endothelial cells. This indicates a between these two pathways Consequently, defined set co-regulate Using identified key predictive for namely MRC1. verify excessive Conclusions: Following might simultaneously upregulating macrophages monocytes contribute progression. Clinical trial Not applicable.

Язык: Английский

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A peripheral system disease—Pulmonary hypertension

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 175, С. 116787 - 116787

Опубликована: Май 23, 2024

Pulmonary hypertension (PH) is a cardiovascular disorder characterized by substantial morbidity and mortality rates. It chronic condition intricate pathogenesis uncontrollable factors. We summarized the pathological effects of estrogen, genetics, neuroinflammation, intestinal microbiota, metabolic reorganization, histone modification on PH. PH not only pulmonary vascular disease, but also systemic disease. The findings emphasize that onset exclusively confined to vasculature, consequently necessitating treatment approaches extend beyond targeting blood vessels. Hence, research mechanism limited target organs such as vessels, focuses exploring other fields (such modification).

Язык: Английский

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