Distinct origins and functions of cardiac orthotopic macrophages

Macrophages are one cell type in the innate immune system. Recent studies involving macrophages have overturned the conventional concept that circulating bone marrow-derived blood mononuclear cells in the adult body continuously replace macrophages residing in the tissues. Investigations using refined technologies have suggested that embryonic hematopoiesis can result in the differentiation into macrophage subgroups in some tissues. In adulthood, these macrophages are self-sustaining via in situ proliferation, with little contribution of circulating bone marrow-derived blood mononuclear cells. Macrophages are integral component of the heart, accounting for 8% of the non-cardiac cells. The use of innovative molecular techniques in paradigm shifting researches has revealed the complexity of cardiac macrophages, including their heterogeneity and ontological diversity. Resident cardiac macrophages modulate the physiological and pathophysiological processes of the cardiovascular system, with distinct and crucial roles in healthy and injured hearts. Their functions include sensing of pathogens, antigen presentation, digesting cell debris, regulating inflammatory responses, generating distinct cytokines, and secreting some regulatory factors. More recent studies have revealed further functions of cardiac macrophages. This review focuses on macrophages within the cardiovascular system. We discuss evidence that has changed our collective view of cardiac macrophage subgroups, and improved our understanding of the different phenotypes, cell surface markers, heterogeneities, origins, developments, and the dynamic and separate roles of these cardiac macrophage subgroups in the steady state and injured hearts. This review may provide novel insights concerning the pathophysiology of cardiac-resident macrophages in cardiovascular diseases and innovative therapeutic strategies that could include the modulation of the role of macrophages in cardiovascular injuries.