Modulators of Macrophage Polarization Influence Healing of the Infarcted Myocardium

Abstract

To diminish heart failure development after acute myocardial infarction (AMI), several preclinical studies have focused on influencing the inflammatory processes in the healing response post-AMI. The initial purpose of this healing response is to clear cell debris of the injured cardiac tissue and to eventually resolve inflammation and support scar tissue formation. This is a well-balanced reaction. However, excess inflammation can lead to infarct expansion, adverse ventricular remodeling and thereby propagate heart failure development. Different macrophage subtypes are centrally involved in both the promotion and resolution phase of inflammation. Modulation of macrophage subset polarization has been described to greatly affect the quality and outcome of healing after AMI. Therefore, it is of great interest to reveal the process of macrophage polarization to support the development of therapeutic targets. The current review summarizes (pre)clinical studies that demonstrate essential molecules involved in macrophage polarization that can be modulated and influence cardiac healing after AMI.

IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2 macrophage polarization and fibroblast activation

“…Within several hours post-MI, the inflammatory response is activated with production of proinflammatory cytokines, also called as M1 cytokines [7, 26]. Following MI, M1 classically polarized macrophages dominate in the LV during the early proinflammatory stage, while during the later anti-inflammatory stage there is a transition to M2 alternatively polarized macrophages [21, 28, 51]. Promoting a timely transition from M1 proinflammation to M2 anti-inflammation may improve MI outcomes.…”

Extracellular vesicles from regenerative human cardiac cells act as potent immune modulators by priming monocytes

“…IL-1RA antagonises IL-1β signalling and thereby suppresses immune responses, which is a known mechanism used by M2-type macrophages [57] or even by murine bone marrow-derived MSCs to induce M2 polarization [58]. In general, the polarization of M2-type macrophages would be beneficial for a potential CardAP-EV product, since the induced macrophages release anti-inflammatory cytokines, chemokines and growth factors [59], which may enhance myocardial repair [60,61]. The detected increase of the M2-type marker CD206, however, might imply either beneficial effects, like an inflammationresolving function [62], or detrimental effects by inducing fibrosis [63].…”

Unified nexus of macrophages and maresins in cardiac reparative mechanisms

“…Macrophages play a vibrant and multitasking role in the innate immune response to injury, and, with the integral role of phagocytosis, macrophages also regulate several wound-healing pathways, including dismantling and removing cell debris, development of mature infarct scar, and angiogenesis (9,19). In vitro, macrophage phenotypes are the classically activated M1 macrophages (proinflammatory type) and the alternatively activated M2 macrophages (anti-inflammatory type or reparative) (20)(21)(22)(23)(24). In a petri dish, macrophage exposure to IFN-g and LPS leads to M1 (inflammatory) polarization, with cytotoxic and antitumoral properties, whereas M2 (reparative or resolving) macrophages display immunoregulatory effects.…”