Macrophages are essential components of the immune system and play a role in the normal functioning of the cardiovascular system. Depending on their origin and phenotype, cardiac macrophages perform various functions. In a steady-state, these cells play a beneficial role in maintaining cardiac homeostasis by defending the body from pathogens and eliminating apoptotic cells, participating in electrical conduction, vessel patrolling, and arterial tone regulation. However, macrophages also take part in adverse cardiac remodeling that could lead to the development and progression of heart failure (HF) in such HF comorbidities as hypertension, obesity, diabetes, and myocardial infarction. Nevertheless, studies on detailed mechanisms of cardiac macrophage function are still in progress, and could enable potential therapeutic applications of these cells. This review aims to present the latest reports on the origin, heterogeneity, and functions of cardiac macrophages in the healthy heart and in cardiovascular diseases leading to HF. The potential therapeutic use of macrophages is also briefly discussed.

The role of cardiac tissue macrophages (cTMs) during pre- and postnatal developmental stages remains in many aspects unknown. We aimed to characterize cTM populations and their potential functions based on surface markers. Our in situ studies of immunostained cardiac tissue specimens of murine fetuses (from E11to E17) revealed that a significant number of embryonic cTMs (phenotyped by CD45, CD68, CD64, F4/80, CD11b, CD206, Lyve-1) resided mostly in the subepicardial space, not in the entire myocardial wall, as observed in adult individuals. cTMs accompanied newly developed blood and lymphatic vessels adhering to vessel walls by cellular processes. A subpopulation of CD68-positive cells was found to form accumulations in areas of massive apoptosis during the outflow tract remodeling and shortening. Flow cytometry analysis at E14 and E17 stages revealed newly defined three subpopulations:CD64^low, CD64^highCD206-and CD64^highCD206+. The levels of mRNA expression for genes related to regulation of angiogenesis (VEGFa, VEGFb, VEGFc, bFGF), lymphangiogenesis (VEGFc) and extracellular matrix (ECM) remodeling (MMP13, Arg1, Ym1/Chil3, Retlna/FIZZ1) differed among the selected populations and/or embryonic stages. Our results demonstrate a diversity of embryonic cTMs and their tissue-specific locations, suggesting their various potential roles in regulating angiogenesis, lymphangiogenesis and ECM remodeling.

Non-coding RNAs (ncRNAs) are a family of RNA molecules that, unlike messenger RNAs, are not templates for protein synthesis but have an essential or regulatory role in this process

Vasculogenesis and hematopoiesis are co-localized in the embryonic body, but precise phenotypes of the cells contributing to these processes are not defined. The aim of this study was to characterize phenotypic profiles and location of putative vasculogenic and hematopoietic cellular progenitors in the embryonic mouse heart. Confocal microscopy, as well as ultrastructural and stereomicroscopic analyses, was performed on immunohistochemical whole-mount-stained or sectioned hearts at stages 11.5–14 dpc. A FASC analysis was conducted to quantify putative vasculogenic and hematopoietic cells. We found subepicardial blood islands in the form of foci of accumulation of cells belonging to erythroblastic and megakaryocytic lineages at various stages of maturation, exhibiting phenotypes: GATA2⁺/CD41⁺, GATA2⁻/CD41⁺, GATA2⁺/CD71⁻, GATA2⁻/CD71⁺, Fli1⁺/CD71⁺, Fli1⁻/CD71⁺, with a majority of cells expressing the Ter119 antigen, but none of them expressing Flk1. The subepicardium and the outflow tract endothelium were recognized to be the areas where progenitor cells were scattered or adjoining the endothelial cells. These progenitor cells were characterized as possessing the following antigens: CD45⁺/Fli1⁺, CD41⁺/Flk1⁺, Flk1⁺/Fli1⁺. A FACS analysis demonstrated that the CD41/Flk1 double-positive population of cells constituted 2.68 % of total cell population isolated from 12.5 dpc hearts. Vessels and tubules were positive for CD31, Flk1, Fli1, Tie2, including blood islands endothelia. The endocardial wall endothelia were found to function as an anchoring apparatus for megakaryocytes releasing platelets into the cardiac cavities. Phenotypic characteristics of vasculogenic (Flk1⁺/Fli1⁺) and hematopoietic (GATA2⁺/CD71⁺, CD41⁺/GATA2⁺) progenitors, as well as the putative hemogenic endothelium (Flk1⁺/CD41⁺) in embryonic mouse hearts, have been presented. Cardiac blood islands, the subepicardium and endothelium of the outflow tract cushions have been defined as areas where these progenitor cells can be found.