Macrophages of the heart: Homeostasis and disease

Cardiac macrophages (CMs) are the most abundant immune cell type in the heart. They are critical for maintaining cardiac homeostasis and in the orchestration of immune responses to ischemic and non-ischemic cardiomyopathies. Their functions are highly heterogeneous and regulated by their tissue microenvironment. CMs have high plasticity, which allows them to perform various functions in the myocardium to bring about homeostasis within the cardiovascular system (CVS). CMs also play critical roles in coronary development and angiogenesis, tissue repair and remodeling, cardiac conduction and in the clearance of necrotic and apoptotic cells. However, there is a paucity of studies on the biology of cardiac macrophages in both steady state and disease, especially in humans. In this review, we discuss the multifaceted roles of CMs in the heart, focusing on their ontogeny, homeostatic functions and immunological responses during inflammation and reparative processes post-injury. We highlight the heterogeneity of CMs in their ontogeny, phenotypes and functions as well as their roles in the pathogenesis of pathological conditions such as myocarditis, myocardial fibrosis and heart failure. Understanding the unique characteristics of cardiac macrophages in the cardiac milieu is critical for the development of macrophage-specific therapeutic interventions to alleviate the global burden of cardiovascular disease (CVD). Therefore, future studies should focus on further improving the understanding of the biology of cardiac macrophages to harness their potential as therapeutic targets for cardiovascular disorders.