The Roles of Macrophages in Heart Regeneration and Repair After Injury

Abstract

Although great advances have been made, the problem of irreversible myocardium loss due to the limited regeneration capacity of cardiomyocytes has not been fully solved. The morbidity and mortality of heart disease still remain high. There are many therapeutic strategies for treating heart disease, while low efficacy and high cost remain challenging. Abundant evidence has shown that both acute and chronic inflammations play a crucial role in heart regeneration and repair following injury. Macrophages, a primary component of inflammation, have attracted much attention in cardiac research in recent decades. The detailed mechanisms of the roles of macrophages in heart regeneration and repair are not completely understood, in part because of their complex subsets, various functions, and intercellular communications. The purpose of this review is to summarize the progress made in the understanding of macrophages, including recent reports on macrophage differentiation, polarization and function, and involvement in heart regeneration and repair. Also, we discuss progress in treatments, which may suggest directions for future research.

Doxorubicin-induced cardiotoxicity is mediated by neutrophils through release of neutrophil elastase

“…Additionally, we briefly monitored levels of another myeloid cell population, monocytes/macrophages, in hearts of Dox-treated mice after neutrophil depletion. Traditionally, macrophages participate in phagocytosis, chemotaxis, secretion and antigen presentation for immune defense and tissue healing ( 31 ). The plastic nature of these cells has rendered their exact function in the cardiac microenvironment post heart damage unclear ( 32 , 33 ).…”

Immune and inflammatory mechanisms of abdominal aortic aneurysm

“…These macrophages are also heterogeneous and can be polarized toward anti-inflammatory or tissue repair subsets. In cardiac repair, they play an important role in tissue regeneration and were shown to remove debris, regulate extracellular matrix (ECM), and stimulate cardiomyocytes proliferation ( 106 ), but their exact role in AAA has not been fully dissected yet. Single cell RNAseq analysis of elastase-driven AAA and healthy vessels revealed that CX3CR1 + (yolk-sac derived) macrophages are the most abundant subset in healthy aorta representing 62.5% of total macrophage population, while bone marrow derived macrophages (CCR2 + Ly6C2 low F4/80 low CD11b low H2-Aa low ) start to dominate in AAA lesions ( 107 ).…”

Inflammatory Cells in Atherosclerosis

“…Macrophages present antigens to cells that initiate inflammation by releasing cytokines; these cells specialize in the detection of dying cells, phagocytosis and the destruction of bacteria [ 62 , 63 , 64 ]. Their role as an immune cell is crucial; involved in all these processes, they allow for the efficient maintenance of efferocytosis, allowing them to aid in resolving inflammation and prevent the formation of the necrotic core in plaques [ 65 ].…”

“…As with many of the cells involved in atherosclerotic lesion formation, macrophages are divided into multiple subsets, M1 and M2 being the two predominant subsets ( Table 2 ). Mox macrophages are known as atherosclerosis-associated macrophages that act as antioxidants, and M4 macrophages reduce phagocytosis and are proinflammatory, playing a minor role [ 62 , 64 ]. In addition, recent studies demonstrated adipose-associated tissue macrophages (ATMs) and tumor-associated macrophages in relation to particular diseases.…”