Cardiac macrophage biology in the steady-state heart, the aging heart, and following myocardial infarction

Figures

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  Fig 1. Macrophage origins in the steady-state heart and the aging heart. In the steady state, the vast majority of resident cardiac macrophages originate from the yolk sac and fetal liver progenitors, with minimal dependence on blood monocytes as a source. In terms of subpopulations, CCR2+ macrophages are replenished by blood monocyte recruitment and local proliferation, whereas CCR2− macrophages are repopulated largely by local proliferation. With age, self-renewal of resident cardiac macrophage declines, and blood monocytes increasingly contribute to the cardiac macrophage population.

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  Fig 2. Macrophage origins in the postmyocardial infarction (MI) heart. Following MI, bone marrow hematopoiesis and extramedullary hematopoiesis by the spleen produce abundant numbers of monocytes, which translocate to the circulation and are recruited to the ischemic heart. In the infarct area, the vast majority of macrophages in the first 3 days are derived from recruitment of blood monocytes, and the renewal of resident macrophages is trivial; in contrast, in the nonischemic remote myocardium, macrophages arise from both local renewal of resident macrophages and recruitment of blood monocytes. The images of cells and organs were obtained from Servier Medical Art (www.servier.com).

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  Fig 3. Proposed post-MI macrophage polarization mechanisms. The integration of 2 mechanisms determines the polarization status of macrophages in the MI heart. (1) M1 and M2 macrophages originate from circulating Ly6Chigh and Ly6Clow monocytes, respectively; Recruitment of Ly6Chigh monocytes depends on CCR2 signaling, whereas recruitment of Ly6Clow monocytes is CX3CR1 dependent; and (2) the mix of pro-M1 and pro-M2 factors existing in the MI myocardium orchestrates macrophage polarization status. MI, myocardial infarction. The images of cells and organs were obtained from Servier Medical Art (www.servier.com).