Resident cardiac macrophages: crucial modulators of cardiac (patho)physiology

Abstract

Resident cardiac macrophages (rcMacs) are integral components of the myocardium where they have key roles for tissue homeostasis and in response to inflammation, tissue injury and remodelling. In this review, we summarize the current knowledge and limitations associated with the rcMacs studies. We describe their specific role and contribution in various processes such as electrical conduction, efferocytosis, inflammation, tissue development, remodelling and regeneration in both the healthy and the disease state. We also outline research challenges and technical complications associated with rcMac research. Recent technological developments and contemporary immunological techniques are now offering new opportunities to investigate the separate contribution of rcMac in respect to recruited monocytes and other cardiac cells. Finally, we discuss new therapeutic strategies, such as drugs or non-coding RNAs, which can influence rcMac phenotype and their response to inflammation. These novel approaches will allow for a deeper understanding of this cardiac endogenous cell type and might lead to the development of more specific and effective therapeutic strategies to boost the heart's intrinsic reparative capacity.

Keywords: Inflammation; Macrophages; Phagocytes; Resident cells.

Fig. 1

Summary of the most commonly used markers for phenotypic characterization of resident and bone-marrow-derived immune cells. The markers’ abbreviations refer to Table 1

Fig. 2

Roles of cardiac macrophages following injury. Cardiac macrophages are involved in cardiac conduction, efferocytosis MerTK-mediated, suppression of maladaptive remodelling, coronary development and maturation and neonatal cardiomyocyte proliferation (SAN sinoatrial node, AVN atrioventricular node)

Fig. 3

Therapeutic approaches to target cardiac macrophages. The most used macrophage-mediated therapeutic strategies are cell therapy, application of nanotechnologies, cytokines/chemokines modulation and non-coding RNAs (MNCs bone marrow mononuclear cells, CDCs cardiosphere-derived cells, MSCs mesenchymal stromal cells, NPs nanoparticles, ncRNA non-coding RNAs, lncRNAs long non-coding RNAs, miRNAs microRNAs)