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.

RhoA: a dubious molecule in cardiac pathophysiology

“…A link between immune responses and cardiomyopathies, including cardiac hypertrophy, was discovered in 1990, when Levin et al observed elevated cytokine levels in patients with heart failure [ 95 ]. Over the years, the involvement of the immune system in cardiac diseases has become an increasingly comprehensive field of research (Reviews: [ 42 , 44 , 69 , 142 ].…”

“…The majority of macrophages in damaged (cardiac) tissue originate from precursor cells circulating in the blood stream and present M1-characteristics [ 69 ]. However, also resident cardiac macrophages (rcMACs) have been described, which reside in healthy myocardium, get activated directly by signals of surrounding cells and present a predominantly M2-phenotype [ 69 , 142 ]. A number of studies have demonstrated a correlation between the number of activated macrophages in the myocardium and the progression of cardiac hypertrophy to fibrosis and heart failure [ 37 , 42 , 51 , 101 , 123 ] (Fig.…”

RhoA Signaling in Immune Cell Response and Cardiac Disease

“…Most macrophages found in damaged (cardiac) tissue originate from myeloid naïve monocytes, which circulate in the blood stream, migrate into affected tissue, and differentiate after activation, which belong to the M1 class [ 36 ]. In addition, one subclass of macrophages, called resident macrophages (rcMACs), resides in specific tissues including myocardium under physiological circumstances [ 36 , 37 ]. These residential cardiac macrophages can get activated directly by signals of surrounding (cardiac) cells and they belong to the M2 class [ 36 , 37 ].…”

RhoA Signaling in Immune Cell Response and Cardiac Disease

“…Most macrophages found in damaged (cardiac) tissue originate from myeloid naïve monocytes, which circulate in the blood stream, migrate into affected tissue, and differentiate after activation, which belong to the M1 class [28]. In addition, one subclass of macrophages, called resident macrophages (rcMACs), resides in specific tissues including myocardium under physiological circumstances [28,29]. These residential cardiac macrophages can get activated directly by signals of surrounding (cardiac) cells and belong to the M2 class [28,29].…”

“…In addition, one subclass of macrophages, called resident macrophages (rcMACs), resides in specific tissues including myocardium under physiological circumstances [28,29]. These residential cardiac macrophages can get activated directly by signals of surrounding (cardiac) cells and belong to the M2 class [28,29]. In this context RhoA-signaling has been linked to macrophage polarization via its main effector ROCK1 in mice cells [30].…”