Macrophage plasticity: signaling pathways, tissue repair, and regeneration

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: Aug. 1, 2024

Abstract Macrophages are versatile immune cells with remarkable plasticity, enabling them to adapt diverse tissue microenvironments and perform various functions. Traditionally categorized into classically activated (M1) alternatively (M2) phenotypes, recent advances have revealed a spectrum of macrophage activation states that extend beyond this dichotomy. The complex interplay signaling pathways, transcriptional regulators, epigenetic modifications orchestrates polarization, allowing respond stimuli dynamically. Here, we provide comprehensive overview the cascades governing focusing on roles Toll‐like receptors, signal transducer activator transcription proteins, nuclear microRNAs. We also discuss emerging concepts metabolic reprogramming trained immunity, contributing their functional adaptability. Macrophage plasticity plays pivotal role in repair regeneration, macrophages coordinating inflammation, angiogenesis, matrix remodeling restore homeostasis. By harnessing potential novel therapeutic strategies targeting polarization could be developed for diseases, including chronic wounds, fibrotic disorders, inflammatory conditions. Ultimately, deeper understanding molecular mechanisms underpinning will pave way innovative regenerative medicine engineering approaches.

Language: Английский

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Metal natural product complex Ru-procyanidins with quadruple enzymatic activity combat infections from drug-resistant bacteria

Acta Pharmaceutica Sinica B, Journal Year: 2024, Volume and Issue: 14(5), P. 2298 - 2316

Published: Jan. 26, 2024

Bacterial infection hampers wound repair by impeding the healing process. Concurrently, inflammation at site triggers production of reactive oxygen species (ROS), causing oxidative stress and damage to proteins cells. This can lead chronic wounds, posing severe risks. Therefore, eliminating bacterial reducing ROS levels are crucial for effective healing. Nanozymes, possessing enzyme-like catalytic activity, convert endogenous substances into highly toxic substances, such as ROS, combat bacteria biofilms without inducing drug resistance. However, current nanozyme model with single enzyme activity falls short meeting complex requirements antimicrobial therapy. Thus, developing nanozymes multiple enzymatic activities is essential. Herein, we engineered a novel metalloenzyme called Ru-procyanidin nanoparticles (Ru-PC NPs) diverse aid infections. Under acidic conditions, due their glutathione (GSH) depletion peroxidase (POD)-like Ru-PC NPs combined H2O2 exhibit excellent antibacterial effects. in neutral environment, NPs, catalase (CAT) decompose O2, alleviating hypoxia ensuring sufficient supply. Furthermore, possess exceptional antioxidant capacity through superior superoxide dismutase (SOD) effectively scavenging excess nitrogen (RNS) environment. maintains balance system prevents inflammation. also promote polarization macrophages from M1 M2, facilitating More importantly, show good biosafety negligible toxicity. In vivo models have confirmed efficacy inhibiting promoting The focus this work highlights quadruple its potential reduce bacteria-infected

Language: Английский

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Lactate and lactylation in cardiovascular diseases: current progress and future perspectives

Metabolism, Journal Year: 2024, Volume and Issue: 158, P. 155957 - 155957

Published: June 21, 2024

Language: Английский

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Macrophage-driven cardiac inflammation and healing: insights from homeostasis and myocardial infarction

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: Oct. 19, 2023

Abstract Early and prompt reperfusion therapy has markedly improved the survival rates among patients enduring myocardial infarction (MI). Nonetheless, resulting adverse remodeling subsequent onset of heart failure remain formidable clinical management challenges represent a primary cause disability in MI worldwide. Macrophages play crucial role immune system regulation wield profound influence over inflammatory repair process following MI, thereby dictating degree injury pathological remodeling. Despite numerous previous biological studies that established classical polarization model for macrophages, classifying them as either M1 pro-inflammatory or M2 pro-reparative this simplistic categorization falls short meeting precision medicine standards, hindering translational advancement research. Recently, advances single-cell sequencing technology have facilitated more exploration macrophage heterogeneity plasticity, opening avenues development targeted interventions to address macrophage-related factors aftermath MI. In review, we provide summary origins, tissue distribution, classification, surface markers. Furthermore, delve into multifaceted roles macrophages maintaining cardiac homeostasis regulating inflammation during post-MI period.

Language: Английский

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The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches

Basic Research in Cardiology, Journal Year: 2023, Volume and Issue: 118(1)

Published: Nov. 8, 2023

Abstract Cardiovascular disease (CVD) is a major threat to human health, accounting for 46% of non-communicable deaths. Glycolysis conserved and rigorous biological process that breaks down glucose into pyruvate, its primary function provide the body with energy intermediate products needed life activities. The non-glycolytic actions enzymes associated glycolytic pathway have long been found be development CVD, typically exemplified by metabolic remodeling in heart failure, which condition exhibits rapid adaptive response hypoxic conditions, occurring early course failure. It mainly characterized decrease oxidative phosphorylation rise pathway, glycolysis considered hallmark remodeling. In addition this, main source cardiomyocytes during ischemia–reperfusion. Not only that, auxiliary pathways glycolysis, such as polyol hexosamine pentose phosphate are also closely related CVD. Therefore, targeting very attractive therapeutic intervention However, relationship between CVD complex, some preclinical studies confirmed does certain degree efficacy, but specific role has yet explored. This article aims summarize current knowledge regarding key (including hexokinase (HK), phosphoglucose isomerase (PGI), phosphofructokinase-1 (PFK1), aldolase (Aldolase), phosphoglycerate metatase (PGAM), enolase (ENO) pyruvate kinase (PKM) lactate dehydrogenase (LDH)) their cardiovascular diseases (e.g., myocardial infarction, atherosclerosis) possible emerging targets.

Language: Английский

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Cardiac macrophages and emerging roles for their metabolism after myocardial infarction

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(18)

Published: Sept. 14, 2023

Interest in cardioimmunology has reached new heights as the experimental cardiology field works to tap unrealized potential of immunotherapy for clinical care. Within this space is cardiac macrophage, a key modulator function health and disease. After myocardial infarction, myeloid macrophages both protect harm heart. To varying degrees, such outcomes are ontogeny heterogeneity, well functional cellular plasticity. Diversity further shaped by extracellular milieu, which fluctuates considerably after coronary occlusion. Ischemic limitation nutrients constrains metabolic immune cells, accumulating evidence supports paradigm whereby macrophage metabolism coupled divergent inflammatory consequences, although heart just emerging. Herein we examine heterogeneous response following ischemic injury, with focus on integrating putative contributions immunometabolism implications therapeutically relevant injury versus repair.

Language: Английский

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Metabolic Reprogramming: A Byproduct or a Driver of Cardiomyocyte Proliferation?

Circulation, Journal Year: 2024, Volume and Issue: 149(20), P. 1598 - 1610

Published: May 13, 2024

Defining mechanisms of cardiomyocyte proliferation should guide the understanding endogenous cardiac regeneration and could lead to novel treatments for diseases such as myocardial infarction. In neonatal heart, energy metabolic reprogramming (phenotypic alteration glucose, fatty acid, amino acid metabolism) parallels cell cycle arrest cardiomyocytes. The occurring shortly after birth is associated with alterations in blood oxygen levels, substrate availability, hemodynamic stress, hormone release. adult infarction causes but these changes cannot stimulate sufficient replace those lost by ischemic injury. Some putative pro-proliferative interventions can induce reprogramming. Recent data show that altering enzymes PKM2 [pyruvate kinase 2], LDHA [lactate dehydrogenase A], PDK4 4], SDH [succinate dehydrogenase], CPT1b [carnitine palmitoyl transferase 1b], or HMGCS2 [3-hydroxy-3-methylglutaryl-CoA synthase 2] partially reverse promotes proliferation. How regulates not clearly defined. possible involve biosynthetic pathways from glycolysis shunts epigenetic regulation induced intermediates. Metabolic manipulation represent a new approach regeneration; however, efficacy manipulations requires optimization, molecular targets need be this review, we summarize features, triggers, regulatory networks responsible discuss current critical determinant

Language: Английский

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Targeting Lactic Acid Modification in Ischemic Heart Diseases: Novel Therapeutics and Mechanism

Journal of Cardiovascular Translational Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 7, 2025

Language: Английский

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Metabolic and Transcriptomic Insights into Controlled Hypothermic Preservation of Human Donor Hearts

The Journal of Heart and Lung Transplantation, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

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Immunometabolism at the Heart of Cardiovascular Disease

JACC Basic to Translational Science, Journal Year: 2023, Volume and Issue: 8(7), P. 884 - 904

Published: April 26, 2023

Immune cell function among the myocardium, now more than ever, is appreciated to regulate cardiac and pathophysiology. This case for both innate immunity, which includes neutrophils, monocytes, dendritic cells, macrophages, as well adaptive T cells B cells. fueled by cell-intrinsic shifts in metabolism, such glycolysis oxidative phosphorylation, metabolite availability, originates from surrounding extracellular milieu varies during ischemia metabolic syndrome. crosstalk with parenchymal cardiomyocytes fibroblasts, also regulated complex cellular circuits. Although our understanding of immunometabolism has advanced rapidly over past decade, part through valuable insights made cultured there remains much learn about contributions vivo directly within myocardium. Insight into fundamental molecular mechanisms holds potential inform interventions that shift balance maladaptive cardioprotective potentially even regenerative. Herein, we review current working immunometabolism, specifically settings sterile ischemic injury or cardiometabolic disease, contribute onset heart failure. We discuss gaps knowledge this context therapeutic implications.

Language: Английский

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