Targeting Macrophage Subsets for Infarct Repair

Abstract

Macrophages are involved in every cardiovascular disease and are an attractive therapeutic target. Macrophage activation is complex and can be either beneficial or deleterious, depending upon its mode of action, its timing, and its duration. An important macrophage characteristic is its plasticity, which enables it to switch from one subset to another. Macrophages, which regulate healing and repair after myocardial infarction, have become a major target for both treatment and diagnosis (theranostic). The aim of the present review is to describe the recent discoveries related to targeting and modulating of macrophage function to improve infarct repair. We will briefly review macrophage polarization, plasticity, heterogeneity, their role in infarct repair, regeneration, and cross talk with mesenchymal cells. Particularly, we will focus on the potential of macrophage targeting in situ by liposomes. The ability to modulate macrophage function could delineate pathways to reactivate the endogenous programs of myocardial regeneration. This will eventually lead to development of small molecules or biologics to enhance the endogenous programs of regeneration and repair.

Functionalized superparamagnetic iron oxide nanoparticles provide highly efficient iron-labeling in macrophages for magnetic resonance–based detection in vivo

“…We observed that ferumoxytol labeling caused a twofold reduction in phagocytosis whereas DEAE-Dex 1:4 labeling had no effect despite providing 10 times more iron uptake. Macrophages display a high degree of plasticity, which has led to the adoption of a simplified classification nomenclature; classical-activation (M1-like) and alternative-activation (M2-like) [26]. Because it may be important for macrophages to retain their phenotypic plasticity to exert their therapeutic effect, we investigated the effect of DEAE-Dex 1:4 labeling on BMDM phenotype via quantification of cell surface markers and gene expression analysis.…”

Mesenchymal stem cells promote macrophage polarization toward M2b-like cells

“…So far, the majority of studies have used adherent cells from peritoneal exudates or spleen isolates [30,31]. Using the standard method for M isolation from the mouse peritoneum based on plastic adherence [22], these cultures contain at least 5-10% of non-M cells [25,32] [13,17,35]. This model has been used to answer two major questions: 1) how MSCs may modify the effect of an inductive environment; 2) whether the shift from one to another MΦ polarization state induced by the instantaneous microenvironment represents an irreversible or a reversible process.…”

Beneficial effects of exosomes secreted by cardiac-derived progenitor cells and other cell types in myocardial ischemia

“…The balance of M1 vs. M2 polarized macrophages has been shown to influence cardiac repair (56)(57)(58). Using rat and pig IR injury models, de Couto et al (59) showed that intracoronary infusion of CDC exosomes, but not inert fibroblast exosomes, reduced the number of CD68 + macrophages within infarcted tissue and modified the polarization state of macrophages.…”