The Role of Innate Immune Cells in Cardiac Injury and Repair: A Metabolic Perspective

Abstract

Purpose of Review Recent technological advances have identified distinct subpopulations and roles of the cardiac innate immune cells, specifically macrophages and neutrophils. Studies on distinct metabolic pathways of macrophage and neutrophil in cardiac injury are expanding. Here, we elaborate on the roles of cardiac macrophages and neutrophils in concomitance with their metabolism in normal and diseased hearts. Recent Findings Single-cell techniques combined with fate mapping have identified the clusters of innate immune cell subpopulations present in the resting and diseased hearts. We are beginning to know about the presence of cardiac resident macrophages and their functions. Summary Resident macrophages perform cardiac homeostatic roles, whereas infiltrating neutrophils and macrophages contribute to tissue damage during cardiac injury with eventual role in repair. Prior studies show that metabolic pathways regulate the phenotypes of the macrophages and neutrophils during cardiac injury. Profiling the metabolism of the innate immune cells, especially of resident macrophages during chronic and acute cardiac diseases, can further the understanding of cardiac immunometabolism.

Advances in the design, generation, and application of tissue-engineered myocardial equivalents

“…As for the recent alarm raised by the World Health Organization on future infectious threats ( Imagining the future, 2022 ), such a modeling approach could have a strong translational impact for prompt understanding of the specific pathomechanism, identification of efficacious pharmacological treatments, and mitigation of the global sociomedical impact of a given microbial biohazard. For such a reason, it would also be necessary to integrate immune cells, as, for example, macrophages, in order to reproduce the full complexity of the physiological cardiac tissue endowed with a resident population of cells deputed to defense ( Swirski and Nahrendorf, 2018 ; Banerjee et al, 2023 ).…”

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“…Among these immune cells, cardiac macrophages assume multifaceted responsibilities encompassing cardiac electrical conduction, angiogenesis, coronary development, and the maintenance of mitochondrial homeostasis [ 35 ]. Essential for sustaining the heart’s homeostasis, cardiac macrophages actively contribute to cellular and extracellular rejuvenation, the clearance of local cellular debris, and the adaptation to tissue strain fluctuations and heightened demands [ 36 ]. Absence of resident macrophages accelerates heart failure [PMID: 34645281] Neutrophils are typically absent in healthy cardiac tissue.…”

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“…18 On the other hand, there is a subset of macrophages (MΦ) in the heart characterized by the expressing CD11b + Ly6C low MHCII low F4/80 high . They play multiple roles in maintaining heart health, including angiogenesis and efferocytosis 19,20 Peroxisome proliferator-activated receptors (PPAR)-α are transcription factors regulated by ligands and are involved in lipid metabolism and the regulation of inflammation. This includes the inhibition of pro-inflammatory cytokines and mediators.…”

“…On the other hand, there is a subset of macrophages (MΦ) in the heart characterized by the expressing CD11b + Ly6C low MHCII low F4/80 high . They play multiple roles in maintaining heart health, including angiogenesis and efferocytosis , …”