Communications between macrophages and cardiomyocytes

Figures

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  Fig. 1. Macrophage Classification Modes. a M0 macrophages can be polarized into M1 macrophages by LPS/IFN-γ stimulation. M1 macrophages are pro-inflammatory subtypes that secrete pro-inflammatory cytokines such as IL-6, IL-12, and IL-1β. M0 macrophages can be polarized into M2 macrophages by IL-4 stimulation. M2 macrophages are associated with inflammation resolution and tissue repair through the secretion of anti-inflammatory cytokines such as IL-10, VEGF, and TGF-β. b Cardiac macrophages can be classified into CCR2+ monocyte-derived macrophage and CX3CR1+ resident macrophage according to their function and origins. Monocyte-derived macrophages are pro-inflammatory and lack reparative activities, whereas resident macrophages promote cardiac repair through anti-inflammatory activities, angiogenesis, and cardiomyocyte proliferation. Furthermore, TIMD4+ macrophages are regarded as a pure population of resident macrophages that reside in cardiac tissue. CD72hi macrophages are pro-inflammatory macrophage subsets

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  Fig. 2. Phagocytic Function of Macrophages (Mø). Macrophages phagocytize CM debris. The phagocytic function of macrophages is regulated by Lgmn and Smad3 signaling. In addition, macrophages engulf dysfunctional mitochondria from CMs via MerTK. Similarly, CMs internalize macrophage-derived mitochondria by clathrin- or lipid raft-mediated endocytosis and induce CM injury by triggering ferroptosis

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  Fig. 3. Modes of Communication between Macrophages and CMs. a Physical interaction. Macrophages interact with neighboring CMs through physical interaction. Macrophages mediate adaptive myocardial remodeling by sensing mechanical stretch of CMs and facilitate CMs electrical conduction by connexin 43. b Paracrine signaling. Macrophages secrete cytokines or other molecules such as IL-1β, OSM, Hepcidin, and Mydgf to regulate CM proliferation, hypertrophy, apoptosis, and electrical conduction. CMs also secrete cytokines such as IL-1β, IL-18, and MCP-1 to recruit macrophages and regulate the phagocytic function of macrophages. c Extracellular vesicles. Macrophages produce vesicles such as miRNA-378a, miRNA-148a, and miRNA-29a to regulate CM death, and CMs also secrete vesicles such as MSC-Exos and CDC-Exos to regulate macrophage polarization and phagocytosis