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. 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.

Keywords: Cardiac homeostasis; Cardiac injury; Immunometabolism; Inflammation; Macrophage; Neutrophil.

Fig. 1

Function of cardiac resident macrophages in the steady-state heart. Cardiac resident macrophages or cMACs are mostly embryonic in origin and perform homeostatic functions in the resting heart. CM cardiomyocyte, cMAC cardiac macrophage, AV atrioventricular. Created with BioRender.com

Fig. 2

Function and metabolism of macrophages and neutrophils in diseased hearts. During acute cardiac injury, neutrophils infiltrate as first responders and recruit monocytes causing further inflammation in heart. Infiltrating macrophages are pro-inflammatory at early-stage cardiac injury and cause further inflammatory cell recruitment while at later stage perform inflammation resolving functions. Resident macrophages are anti-inflammatory and carry out reparative functions after cardiac injury. Infiltrating neutrophils induce monocyte recruitment during chronic cardiac remodeling. Resident macrophages preserve cardiac function during chronic cardiac remodeling and promote angiogenesis while infiltrating macrophages cause fibrosis and cardiac dysfunction. While the infiltrating neutrophils and pro-inflammatory macrophages are glycolytic in the setting of acute cardiac injury, the resolving macrophages depend on mitochondrial oxidative phosphorylation or OXPHOS. Created with BioRender.com