{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T21:17:25Z","timestamp":1791580645299,"version":"4.3.4"},"reference-count":121,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Sepsis-related myocardial injury (SRMI) is a major cause of death in critically ill patients, with pathogenesis extending beyond inflammation to encompass dysregulated immunometabolic crosstalk. This review elucidates macrophage metabolic reprogramming as a central mechanism driving SRMI, detailing how a shift to aerobic glycolysis fuels pro-inflammatory responses, while oxidative phosphorylation supports reparative functions. We emphasize that metabolites like succinate, itaconate, and lactate act as potent signaling molecules, orchestrating epigenetic changes and inflammatory pathways. Furthermore, we deconstruct the critical immunometabolic dialogue mediated by extracellular vesicles (EVs) and signaling cascades among macrophages, cardiomyocytes, and endothelial cells. Translating these insights, we evaluate next-generation therapeutic strategies aimed at this immunometabolic axis, including precision small-molecule modulators, nucleic acid-based technologies, and biologics. These approaches represent a promising strategic shift from non-specific immunosuppression toward targeted immunometabolic modulation. This synthesis provides a foundational framework for understanding SRMI and charts a roadmap for developing novel precision medicine interventions to improve patient outcomes.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1779575","type":"journal-article","created":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:37:26Z","timestamp":1773207446000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["The immunometabolic axis of sepsis-related myocardial injury: macrophage reprogramming as a central mechanism and therapeutic target"],"prefix":"10.3389","volume":"17","author":[{"given":"Yuyang","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Emergency Intensive Care Unit (EICU), The Second People\u2019s Hospital of Guiyang (Jinyang Hospital)\/The Affiliated Jinyang Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]},{"name":"Department of Intensive Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Bi","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Emergency Intensive Care Unit (EICU), The Second People\u2019s Hospital of Guiyang (Jinyang Hospital)\/The Affiliated Jinyang Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Emergency Intensive Care Unit (EICU), The Second People\u2019s Hospital of Guiyang (Jinyang Hospital)\/The Affiliated Jinyang Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Intensive Care Unit (EICU), The Second People\u2019s Hospital of Guiyang (Jinyang Hospital)\/The Affiliated Jinyang Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyu","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, The Affiliated Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiyun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Intensive Care Unit (EICU), The Second People\u2019s Hospital of Guiyang (Jinyang Hospital)\/The Affiliated Jinyang Hospital of Guizhou Medical University","place":["Guiyang, Guizhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.24505","article-title":"Effect of vitamin C, thiamine, and hydrocortisone on ventilator- and vasopressor-free days in patients with sepsis: the VICTAS randomized clinical trial","volume":"325","author":"Sevransky","year":"2021","journal-title":"JAMA"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.jointm.2021.11.004","article-title":"Septic cardiomyopathy: Diagnosis and management","volume":"2","author":"Boissier","year":"2021","journal-title":"J Intensive Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-00492-2","article-title":"Pathophysiology of sepsis-induced cardiomyopathy","volume":"18","author":"Hollenberg","year":"2021","journal-title":"Nat Rev Cardiol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ccc.2017.08.002","article-title":"Immune activation in sepsis","volume":"34","author":"Conway-Morris","year":"2017","journal-title":"Crit Care Clin"},{"key":"B7","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s40779-022-00422-y","article-title":"Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options","volume":"9","author":"Liu","year":"2022","journal-title":"Mil Med Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.06.003","article-title":"High-mobility group box 1 (HMGB1) impaired cardiac excitation-contraction coupling by enhancing the sarcoplasmic reticulum (SR) Ca(2+) leak through TLR4-ROS signaling in cardiomyocytes","volume":"74","author":"Zhang","year":"2014","journal-title":"J Mol Cell Cardiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"396","year":"2020","journal-title":"Lancet"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.10.011","article-title":"The role of mitochondria in sepsis-induced cardiomyopathy","volume":"1865","author":"Stanzani","year":"2018","journal-title":"Biochim Biophys Acta Mol Basis Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-024-07586-2","article-title":"Understanding, assessing and treating immune, endothelial and haemostasis dysfunctions in bacterial sepsis","volume":"50","author":"Girardis","year":"2024","journal-title":"Intensive Care Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201910-1911TR","article-title":"Endothelial responses in sepsis","volume":"202","author":"Joffre","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.002","article-title":"DAMPs and DAMP-sensing receptors in inflammation and diseases","volume":"57","author":"Ma","year":"2024","journal-title":"Immunity"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-025-08049-y","article-title":"Cardiogenic shock: diagnosis, phenotyping and management","volume":"51","author":"M\u00f8ller","year":"2025","journal-title":"Intensive Care Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/cells12212555","article-title":"Myocardial mitochondrial DNA drives macrophage inflammatory response through STING signaling in coxsackievirus B3-induced viral myocarditis","volume":"12","author":"Qin","year":"2023","journal-title":"Cells"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.70559","article-title":"Roles and therapeutic targeting of exosomes in sepsis-induced cardiomyopathy","volume":"29","author":"Fan","year":"2025","journal-title":"J Cell Mol Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.86832","article-title":"Extracellular vesicles in sepsis: pathogenic roles, organ damage, and therapeutic implications","volume":"20","author":"An","year":"2023","journal-title":"Int J Med Sci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2316-7","article-title":"Deciphering human macrophage development at single-cell resolution","volume":"582","author":"Bian","year":"2020","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.10.007","article-title":"Macrophages in health and disease","volume":"185","author":"Park","year":"2022","journal-title":"Cell"},{"key":"B20","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/s41392-023-01452-1","article-title":"Macrophages in immunoregulation and therapeutics","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2016.70","article-title":"A guide to immunometabolism for immunologists","volume":"16","author":"O\u2019Neill","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-022-00715-5","article-title":"TREM2hi resident macrophages protect the septic heart by maintaining cardiomyocyte homeostasis","volume":"5","author":"Zhang","year":"2023","journal-title":"Nat Metab"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jjcc.2025.09.003","article-title":"11\u03b2-HSD1 inhibitor alleviates sepsis-induced cardiac dysfunction by regulating macrophage polarization via the AMPK\/mTOR autophagy pathway","author":"Zhang","year":"2025","journal-title":"J Cardiol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"155175","DOI":"10.1016\/j.phymed.2023.155175","article-title":"Chicoric acid ameliorates sepsis-induced cardiomyopathy via regulating macrophage metabolism reprogramming","volume":"123","author":"Sun","year":"2023","journal-title":"Phytomedicine"},{"key":"B25","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1038\/s41392-025-02124-y","article-title":"Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets","volume":"10","author":"Guan","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B26","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/s41586-023-06002-x","article-title":"Physiology and diseases of tissue-resident macrophages","volume":"618","author":"Lazarov","year":"2023","journal-title":"Nature"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0059-x","article-title":"The human heart contains distinct macrophage subsets with divergent origins and functions","volume":"24","author":"Bajpai","year":"2018","journal-title":"Nat Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.11.019","article-title":"Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation","volume":"40","author":"Epelman","year":"2014","journal-title":"Immunity"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.12.6166","article-title":"M-1\/M-2 macrophages and the Th1\/Th2 paradigm","volume":"164","author":"Mills","year":"2000","journal-title":"J Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau0964","article-title":"Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches","volume":"363","author":"Chakarov","year":"2019","journal-title":"Science"},{"key":"B31","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1038\/s41392-024-01840-1","article-title":"Macrophages in cardiovascular diseases: molecular mechanisms and therapeutic targets","volume":"9","author":"Chen","year":"2024","journal-title":"Signal Transduct Target Ther"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1606401","article-title":"LILRA5+ macrophages drive early oxidative stress surge in sepsis: a single-cell transcriptomic landscape with therapeutic implications","volume":"15","author":"Xu","year":"2025","journal-title":"Front Cell Infect Microbiol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.124.325147","article-title":"Bacterial infections shape cardiac macrophages\u2019 Response to ischemia","volume":"137","author":"Geissen","year":"2025","journal-title":"Circ Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.607650","article-title":"Immunometabolism of macrophages in bacterial infections","volume":"10","author":"Galli","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1160719","article-title":"Advances in the role of STAT3 in macrophage polarization","volume":"14","author":"Xia","year":"2023","journal-title":"Front Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000002683","article-title":"Macrophages in septic cardiomyopathy: heterogeneity, function, and therapy","author":"Wu","year":"2025","journal-title":"Shock"},{"key":"B37","article-title":"Tumor necrosis factor depresses myocardial cell function: results using an in vitro assay of myocyte performance","volume":"37","author":"Hollenberg","year":"1989","journal-title":"Clin Res"},{"key":"B38","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/s41392-025-02178-y","article-title":"Deep insight into cytokine storm: from pathogenesis to treatment","volume":"10","author":"Nie","year":"2025","journal-title":"Signal Transduct Target Ther"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25021082","article-title":"The role of pro-inflammatory cytokines in the pathogenesis of cardiovascular disease","volume":"25","author":"Zhang","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00894-6","article-title":"The multifunctional protein HMGB1: 50 years of discovery","volume":"23","author":"Tang","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3CE1216-510R","article-title":"Editorial: Modulation of HMGB1 holds promise for managing sepsis immune paralysis","volume":"101","author":"Blumental-Perry","year":"2017","journal-title":"J Leukoc Biol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1172\/JCI24159","article-title":"Altered intracellular Ca2+ handling in heart failure","volume":"115","author":"Yano","year":"2005","journal-title":"J Clin Invest"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-020-0394-8","article-title":"Intracellular calcium leak in heart failure and atrial fibrillation: a unifying mechanism and therapeutic target","volume":"17","author":"Dridi","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1152\/physrev.00018.2010","article-title":"CaMKII in the cardiovascular system: sensing redox states","volume":"91","author":"Erickson","year":"2011","journal-title":"Physiol Rev"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-025-00687-1","article-title":"Excessive HIF-1\u03b1 driven by phospholipid metabolism causes septic cardiomyopathy through cytopathic hypoxia","volume":"4","author":"Watanabe","year":"2025","journal-title":"Nat Cardiovasc Res"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0052-8","article-title":"The machineries, regulation and cellular functions of mitochondrial calcium","volume":"19","author":"Giorgi","year":"2018","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s42255-025-01224-x","article-title":"Pro-inflammatory macrophages produce mitochondria-derived superoxide by reverse electron transport at complex I that regulates IL-1\u03b2 release during NLRP3 inflammasome activation","volume":"7","author":"Casey","year":"2025","journal-title":"Nat Metab"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1097\/CM9.0000000000003189","article-title":"Interaction between macrophages and ferroptosis: Metabolism, function, and diseases","volume":"138","author":"Jiang","year":"2024","journal-title":"Chin Med J (Engl)"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2239","article-title":"ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition","volume":"13","author":"Doll","year":"2016","journal-title":"Nat Chem Biol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0462-8","article-title":"Redox lipid reprogramming commands susceptibility of macrophages and microglia to ferroptotic death","volume":"16","author":"Kapralov","year":"2020","journal-title":"Nat Chem Biol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2023.10.011","article-title":"Ceria nanozyme coordination with curcumin for treatment of sepsis-induced cardiac injury by inhibiting ferroptosis and inflammation","volume":"63","author":"Jiang","year":"2023","journal-title":"J Adv Res"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu146","article-title":"RIP3, a kinase promoting necroptotic cell death, mediates adverse remodelling after myocardial infarction","volume":"103","author":"Luedde","year":"2014","journal-title":"Cardiovasc Res"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2018.00721","article-title":"The role of necroptosis in cardiovascular disease","volume":"9","author":"Zhe-Wei","year":"2018","journal-title":"Front Pharmacol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309326","article-title":"Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis","volume":"120","author":"F\u00f6rstermann","year":"2017","journal-title":"Circ Res"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.125.075150","article-title":"Targeting calcium regulation for heart failure and arrhythmia therapeutics: A critical review","volume":"152","author":"Redel-Traub","year":"2025","journal-title":"Circulation"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1172\/JCI184134","article-title":"Mechanisms of postischemic cardiac death and protection following myocardial injury","volume":"135","author":"Mastoor","year":"2025","journal-title":"J Clin Invest"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1042\/BST0340232","article-title":"Calcium, mitochondria and reperfusion injury: a pore way to die","volume":"34","author":"Halestrap","year":"2006","journal-title":"Biochem Soc Trans"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000156461.81529.D7","article-title":"Increased nitration of sarcoplasmic reticulum Ca2+-ATPase in human heart failure","volume":"111","author":"Lokuta","year":"2005","journal-title":"Circulation"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22136995","article-title":"Macrophage polarization states in the tumor microenvironment","volume":"22","author":"Boutilier","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901698","article-title":"Substrate fate in activated macrophages: a comparison between innate, classic, and alternative activation","volume":"185","author":"Rodr\u00edguez-Prados","year":"2010","journal-title":"J Immunol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.08.012","article-title":"Glycolytic stimulation is not a requirement for M2 macrophage differentiation","volume":"28","author":"Wang","year":"2018","journal-title":"Cell Metab"},{"key":"B62","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1084\/jem.20151570","article-title":"Immunometabolism governs dendritic cell and macrophage function","volume":"213","author":"O\u2019Neill","year":"2015","journal-title":"J Exp Med"},{"key":"B63","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.cmet.2015.01.017","article-title":"Pyruvate kinase M2 regulates hif-1\u03b1 Activity and IL-1\u03b2 Induction and is a critical determinant of the warburg effect in LPS-activated macrophages","volume":"21","author":"Palsson-McDermott","year":"2015","journal-title":"Cell Metab"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00806-5","article-title":"The transcription factor KLF14 regulates macrophage glycolysis and immune function by inhibiting HK2 in sepsis","volume":"19","author":"Yuan","year":"2022","journal-title":"Cell Mol Immunol"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00061","article-title":"Metabolism supports macrophage activation","volume":"8","author":"Langston","year":"2017","journal-title":"Front Immunol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.064","article-title":"Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages","volume":"167","author":"Mills","year":"2016","journal-title":"Cell"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2025.03.004","article-title":"Gang of 3: How the Krebs cycle-linked metabolites itaconate, succinate, and fumarate regulate macrophages and inflammation","volume":"37","author":"P\u00e5lsson-McDermott","year":"2025","journal-title":"Cell Metab"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.522037","article-title":"Metabolic reprogramming of macrophages: glucose transporter 1 (GLUT1)-mediated glucose metabolism drives a proinflammatory phenotype","volume":"289","author":"Freemerman","year":"2014","journal-title":"J Biol Chem"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40364-020-00251-y","article-title":"Metabolic reprogramming in macrophage responses","volume":"9","author":"Liu","year":"2021","journal-title":"biomark Res"},{"key":"B70","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.canlet.2019.03.015","article-title":"Metabolic reprogramming of macrophages during infections and cancer","volume":"452","author":"Wang","year":"2019","journal-title":"Cancer Lett"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.95","article-title":"AMPK: guardian of metabolism and mitochondrial homeostasis","volume":"19","author":"Herzig","year":"2017","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.3390\/cells11203215","article-title":"PPAR-\u03b3 Partial agonists in disease-fate decision with special reference to cancer","volume":"11","author":"Ballav","year":"2022","journal-title":"Cells"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.737776","article-title":"PPAR-\u03b3 Modulators as current and potential cancer treatments","volume":"11","author":"Chi","year":"2021","journal-title":"Front Oncol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ado5887","article-title":"Mitochondrial fatty acid oxidation drives senescence","volume":"10","author":"Yamauchi","year":"2024","journal-title":"Sci Adv"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3704","article-title":"Mitochondria are the powerhouses of immunity","volume":"18","author":"Mills","year":"2017","journal-title":"Nat Immunol"},{"key":"B76","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.it.2017.03.001","article-title":"Macrophage immunometabolism: where are we (Going)","volume":"38","author":"Van den Bossche","year":"2017","journal-title":"Trends Immunol"},{"key":"B77","doi-asserted-by":"publisher","first-page":"115172","DOI":"10.1016\/j.celrep.2024.115172","article-title":"Metabolic reprogramming of macrophages by PKM2 promotes IL-10 production via adenosine","volume":"44","author":"Toller-Kawahisa","year":"2025","journal-title":"Cell Rep"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1678-1","article-title":"Metabolic regulation of gene expression by histone lactylation","volume":"574","author":"Zhang","year":"2019","journal-title":"Nature"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1038\/nature25986","article-title":"Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1","volume":"556","author":"Mills","year":"2018","journal-title":"Nature"},{"key":"B80","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/s13054-018-2043-8","article-title":"Pathophysiology, echocardiographic evaluation, biomarker findings, and prognostic implications of septic cardiomyopathy: a review of the literature","volume":"22","author":"Ehrman","year":"2018","journal-title":"Crit Care"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces IL-1\u03b2 through HIF-1\u03b1","volume":"496","author":"Tannahill","year":"2013","journal-title":"Nature"},{"key":"B82","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1038\/s42255-020-0210-0","article-title":"Comparative evaluation of itaconate and its derivatives reveals divergent inflammasome and type I interferon regulation in macrophages","volume":"2","author":"Swain","year":"2020","journal-title":"Nat Metab"},{"key":"B83","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1038\/s41467-025-56666-4","article-title":"ER-mitochondria contacts mediate lipid radical transfer via RMDN3\/PTPIP51 phosphorylation to reduce mitochondrial oxidative stress","volume":"16","author":"Shiiba","year":"2025","journal-title":"Nat Commun"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abi8602","article-title":"Lactate supports a metabolic-epigenetic link in macrophage polarization","volume":"7","author":"Noe","year":"2021","journal-title":"Sci Adv"},{"key":"B85","doi-asserted-by":"publisher","first-page":"3230","DOI":"10.1038\/s41467-025-58563-2","article-title":"Lactate activates trained immunity by fueling the tricarboxylic acid cycle and regulating histone lactylation","volume":"16","author":"Cai","year":"2025","journal-title":"Nat Commun"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.01.010","article-title":"Lycorine protects against septic myocardial injury by activating AMPK-related pathways","volume":"197","author":"Zhao","year":"2023","journal-title":"Free Radic Biol Med"},{"key":"B87","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/jcp.30527","article-title":"Pathogenetic mechanisms of septic cardiomyopathy","volume":"237","author":"Wang","year":"2021","journal-title":"J Cell Physiol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-09682-9","article-title":"Ribonucleotide incorporation into mitochondrial DNA drives inflammation","volume":"647","author":"Bahat","year":"2025","journal-title":"Nature"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2025.07.012","article-title":"Mitochondria reactive oxygen species signaling-dependent immune responses in macrophages and T cells","volume":"58","author":"Weinberg","year":"2025","journal-title":"Immunity"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201488104","article-title":"A new pathway for mitochondrial quality control: mitochondrial-derived vesicles","volume":"33","author":"Sugiura","year":"2014","journal-title":"EMBO J"},{"key":"B91","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s13024-018-0262-8","article-title":"The Trem2 R47H variant confers loss-of-function-like phenotypes in Alzheimer\u2019s disease","volume":"13","author":"Cheng-Hathaway","year":"2018","journal-title":"Mol Neurodegener"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1038\/nature10992","article-title":"Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure","volume":"485","author":"Oka","year":"2012","journal-title":"Nature"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.10.030","article-title":"Astragaloside IV alleviates septic myocardial injury through DUSP1-Prohibitin 2 mediated mitochondrial quality control and ER-autophagy","volume":"75","author":"Wang","year":"2024","journal-title":"J Adv Res"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2025.03.003","article-title":"Mitochondria-organelle crosstalk in establishing compartmentalized metabolic homeostasis","volume":"85","author":"Chen","year":"2025","journal-title":"Mol Cell"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J Cell Biol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.024590","article-title":"Exosomal microRNA transfer into macrophages mediates cellular postconditioning","volume":"136","author":"de Couto","year":"2017","journal-title":"Circulation"},{"key":"B97","doi-asserted-by":"publisher","first-page":"tkae042","DOI":"10.1093\/burnst\/tkae042","article-title":"Dexmedetomidine regulates exosomal miR-29b-3p from macrophages and alleviates septic myocardial injury by promoting autophagy in cardiomyocytes via targeting glycogen synthase kinase 3\u03b2","volume":"12","author":"Yu","year":"2024","journal-title":"Burns Trauma"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1080\/08923973.2021.1955920","article-title":"Bone marrow-mesenchymal stem cell-derived exosomal microRNA-141 targets PTEN and activates \u03b2-catenin to alleviate myocardial injury in septic mice","volume":"43","author":"Pei","year":"2021","journal-title":"Immunopharmacol Immunotoxicol"},{"key":"B99","volume-title":"The role and mechanism of placental mesenchymal stem cell derived exosomes carrying miR-126a-3p in sepsis-induced myocardial depression","author":"Wang","year":"2023"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2021.10.027","article-title":"Inhibition of microRNA-494-3p activates Wnt signaling and reduces proinflammatory macrophage polarization in atherosclerosis","volume":"26","author":"van Ingen","year":"2021","journal-title":"Mol Ther Nucleic Acids"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2564","article-title":"Exosomal miR-146a contributes to the enhanced therapeutic efficacy of interleukin-1\u03b2-primed mesenchymal stem cells against sepsis","volume":"35","author":"Song","year":"2017","journal-title":"Stem Cells"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2025.01.073","article-title":"Mannose-modified exosomes loaded with MiR-23b-3p target alveolar macrophages to alleviate acute lung injury in Sepsis","volume":"379","author":"Lin","year":"2025","journal-title":"J Control Release"},{"key":"B103","doi-asserted-by":"publisher","first-page":"117180","DOI":"10.1016\/j.biopha.2024.117180","article-title":"Endothelial dysfunction: Pathophysiology and therapeutic targets for sepsis-induced multiple organ dysfunction syndrome","volume":"178","author":"Tang","year":"2024","journal-title":"BioMed Pharmacother"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061489","article-title":"The HSP90 inhibitor, AUY-922, protects and repairs human lung microvascular endothelial cells from hydrochloric acid-induced endothelial barrier dysfunction","volume":"10","author":"Colunga Biancatelli","year":"2021","journal-title":"Cells"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012-0496OC","article-title":"Heat shock protein 90 inhibitors prevent LPS-induced endothelial barrier dysfunction by disrupting RhoA signaling","volume":"50","author":"Joshi","year":"2014","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2008.06.008","article-title":"The heterogeneity of the microcirculation in critical illness","volume":"29","author":"Klijn","year":"2008","journal-title":"Clin Chest Med"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000001577","article-title":"Spock2 functions as a key time-series gene of endothelial cells in sepsis-induced cardiomyopathy","volume":"84","author":"Zhang","year":"2024","journal-title":"J Cardiovasc Pharmacol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2025.1559064","article-title":"Emerging mechanisms and implications of m6A in CVDs: potential applications of natural products","volume":"12","author":"Wang","year":"2025","journal-title":"Front Cardiovasc Med"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2022.887838","article-title":"N6-methyladenosine RNA methylation in cardiovascular diseases","volume":"9","author":"Liu","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn121430-20200211-00177","article-title":"Research progress of metabolism reprogramming in regulating macrophage polarization","volume":"32","author":"Liu","year":"2020","journal-title":"Zhonghua Wei Zhong Bing Ji Jiu Yi Xue"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2784-1","article-title":"Biochemistry of proinflammatory macrophage activation","volume":"75","author":"Nonnenmacher","year":"2018","journal-title":"Cell Mol Life Sci"},{"key":"B112","doi-asserted-by":"publisher","first-page":"109698","DOI":"10.1016\/j.clim.2023.109698","article-title":"ATF4 knockdown in macrophage impairs glycolysis and mediates immune tolerance by targeting HK2 and HIF-1\u03b1 ubiquitination in sepsis","volume":"254","author":"Liu","year":"2023","journal-title":"Clin Immunol"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70315","article-title":"Myeloid deficiency of Z-DNA binding protein 1 restricts septic cardiomyopathy via promoting macrophage polarisation towards the M2-subtype","volume":"15","author":"Shi","year":"2025","journal-title":"Clin Transl Med"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.3390\/biom13050770","article-title":"Glucose transporter glut1-dependent metabolic reprogramming regulates lipopolysaccharide-induced inflammation in RAW264.7 macrophages","volume":"13","author":"Cornwell","year":"2023","journal-title":"Biomolecules"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1452993","article-title":"Targeting AMP-activated protein kinase in sepsis","volume":"15","author":"Yumoto","year":"2024","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-025-01985-x","article-title":"Metabolic remodelling produces fumarate via the aspartate-argininosuccinate shunt in macrophages as an antiviral defence","volume":"10","author":"Xia","year":"2025","journal-title":"Nat Microbiol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c18345","article-title":"Treatment of acute liver injury through selective tropism of high mobility group box 1 gene-silenced large peritoneal macrophages","volume":"19","author":"Oza","year":"2025","journal-title":"ACS Nano"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.7555\/JBR.36.20220212","article-title":"Knockdown of 11\u03b2-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK\/SIRT1\/PGC-1\u03b1 pathway","volume":"37","author":"Zhu","year":"2023","journal-title":"J BioMed Res"},{"key":"B119","doi-asserted-by":"publisher","first-page":"0663","DOI":"10.34133\/research.0663","article-title":"A self-assembled metabolic regulator reprograms macrophages to combat cytokine storm and boost sepsis immunotherapy","volume":"8","author":"Zhuang","year":"2025","journal-title":"Res (Wash D C)"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202507970","article-title":"Decoupling Half-Process Assisted Mitochondrial Transplantation via Self-Stripping pHLIP Boosts Macrophages Reprogramming for Inflammation Resolution","volume":"21","author":"He","year":"2025","journal-title":"Small"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202503252","article-title":"Artificial intelligence-enabled quantitative assessment and intervention for heart inflammation model organoids","volume":"64","author":"Lin","year":"2025","journal-title":"Angew Chem Int Ed Engl"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1779575\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T05:37:28Z","timestamp":1773207448000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1779575\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,11]]},"references-count":121,"alternative-id":["10.3389\/fimmu.2026.1779575"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1779575","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,11]]},"article-number":"1779575"}}