Abstract:IntroductionMetabolic reprogramming from glycolysis to the mitochondrial tricarboxylic acid (TCA) cycle and oxidative phosphorylation may mediate macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. We hypothesized that changes in cardiac macrophage glucose metabolism would reflect polarization status after myocardial infarction (MI), ranging from the early inflammatory phase to the later wound healing phase.MethodsMI was induced by permanent ligation of the left coronary… Show more
“…Pro-reparative macrophages appear later and primarily engage in efferocytosis, collagen deposition, and ECM synthesis. Glycolytic metabolism analysis also corroborated this, as gene expression related to glycolysis increased 1 day after MI, TCA gene expression increased on day 3 and day 7 after MI, and PPP gene expression also increased on day 7 after MI, whereas this metabolic reprogramming phenomenon is observed in monocyte-derived macrophages rather than RTMs [ 123 ]. Fig.…”
Section: Macrophages In the Development Of MImentioning
Early and prompt reperfusion therapy has markedly improved the survival rates among patients enduring myocardial infarction (MI). Nonetheless, the resulting adverse remodeling and the subsequent onset of heart failure remain formidable clinical management challenges and represent a primary cause of disability in MI patients worldwide. Macrophages play a crucial role in immune system regulation and wield a profound influence over the inflammatory repair process following MI, thereby dictating the degree of myocardial injury and the subsequent pathological remodeling. Despite numerous previous biological studies that established the classical polarization model for macrophages, classifying them as either M1 pro-inflammatory or M2 pro-reparative macrophages, this simplistic categorization falls short of meeting the precision medicine standards, hindering the translational advancement of clinical research. Recently, advances in single-cell sequencing technology have facilitated a more profound exploration of macrophage heterogeneity and plasticity, opening avenues for the development of targeted interventions to address macrophage-related factors in the aftermath of MI. In this review, we provide a summary of macrophage origins, tissue distribution, classification, and surface markers. Furthermore, we delve into the multifaceted roles of macrophages in maintaining cardiac homeostasis and regulating inflammation during the post-MI period.
“…Pro-reparative macrophages appear later and primarily engage in efferocytosis, collagen deposition, and ECM synthesis. Glycolytic metabolism analysis also corroborated this, as gene expression related to glycolysis increased 1 day after MI, TCA gene expression increased on day 3 and day 7 after MI, and PPP gene expression also increased on day 7 after MI, whereas this metabolic reprogramming phenomenon is observed in monocyte-derived macrophages rather than RTMs [ 123 ]. Fig.…”
Section: Macrophages In the Development Of MImentioning
Early and prompt reperfusion therapy has markedly improved the survival rates among patients enduring myocardial infarction (MI). Nonetheless, the resulting adverse remodeling and the subsequent onset of heart failure remain formidable clinical management challenges and represent a primary cause of disability in MI patients worldwide. Macrophages play a crucial role in immune system regulation and wield a profound influence over the inflammatory repair process following MI, thereby dictating the degree of myocardial injury and the subsequent pathological remodeling. Despite numerous previous biological studies that established the classical polarization model for macrophages, classifying them as either M1 pro-inflammatory or M2 pro-reparative macrophages, this simplistic categorization falls short of meeting the precision medicine standards, hindering the translational advancement of clinical research. Recently, advances in single-cell sequencing technology have facilitated a more profound exploration of macrophage heterogeneity and plasticity, opening avenues for the development of targeted interventions to address macrophage-related factors in the aftermath of MI. In this review, we provide a summary of macrophage origins, tissue distribution, classification, and surface markers. Furthermore, we delve into the multifaceted roles of macrophages in maintaining cardiac homeostasis and regulating inflammation during the post-MI period.
“…Glycolytic monocytes are observed in both infectious settings and inflammatory diseases. Glycolysis fuels the inflammatory program of monocytes in rheumatoid arthritis ( 40 ), in patients with atherosclerotic coronary artery disease ( 41 ), in myocardial infarction ( 42 ), in Chagas disease ( 43 ), and in malaria ( 44 ).…”
IntroductionObesity is associated with a plethora of health complications, including increased susceptibility to infections or decreased vaccine efficacy, partly due to dysregulated immune responses. Monocytes play a crucial role in innate immunity, yet their functional alterations in obesity remain poorly understood.MethodsHere, we employed proteomic and metabolomic analyses to investigate monocyte characteristics in individuals with overweight, obesity, impaired glucose tolerance (IGT), and type 2 diabetes (T2D), compared to lean donors.Results and discussionOur results revealed distinct molecular signatures in monocytes from individuals with obesity, with significant alterations in pathways related to metabolism, cellular migration, and phagocytosis. Moreover, LPS-induced activation of monocytes unveiled heightened metabolic reprogramming towards glycolysis in subjects with obesity accompanied by dysregulated cytokine responses and elevated oxidative stress. Additionally, monocytes from donors with obesity exhibited increased lipid droplet accumulation. These findings shed light on the immunometabolic dysregulation underlying obesity-associated immune dysfunction, highlighting potential targets for therapeutic intervention.
“…M1-like macrophages, Ly6C-high monocytes, Th1/Th17 cells) rely mainly on glycolysis, while anti-inflammatory/reparative subsets (M2-like macrophages, Ly6C-low/resident cardiac macrophages, Tregs) rely more on mitochondrial oxidative phosphorylation (OXPHOS). Glycolysis can allow cells to survive in a hypoxic environment, such as the ischemic heart, and permits activation of the pentose phosphate pathway ( 4 ). Macrophages and T cells can also program their metabolism to glycolysis even when oxygen is present, a phenomenon known as the Warburg effect.…”
Section: Role Of Immune Cells and Immunometabolism In Cardiac Injury ...mentioning
confidence: 99%
“…EVs enriched with ribose-5-phosphate and pentose phosphate pathways enzymes, may support immune cell proliferation during MI ( 4 , 56 ). Indeed, many other small sugar, amino acid, and nucleotide metabolites have been discovered in EVs, depending on the source, size, and cardiovascular disease context ( 60 ).…”
Section: Potential Interactions Of Extracellular Vesicles and Immune ...mentioning
Recent evidence from our lab and others suggests that metabolic reprogramming of immune cells drives changes in immune cell phenotypes along the inflammatory-to-reparative spectrum and plays a critical role in mediating the inflammatory responses to cardiac injury (e.g. hypertension, myocardial infarction). However, the factors that drive metabolic reprogramming in immune cells are not fully understood. Extracellular vesicles (EVs) are recognized for their ability to transfer cargo such as microRNAs from remote sites to influence cardiac remodeling. Furthermore, conditions such as obesity and metabolic syndrome, which are implicated in the majority of cardiovascular disease (CVD) cases, can skew production of EVs toward pro-inflammatory phenotypes. In this mini-review, we discuss the mechanisms by which EVs may influence immune cell metabolism during cardiac injury and factors associated with obesity and the metabolic syndrome that can disrupt normal EV function. We also discuss potential sources of cardio-protective and anti-inflammatory EVs, such as brown adipose tissue. Finally, we discuss implications for future therapeutics.
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