The Non-cardiomyocyte Cells of the Heart. Their Possible Roles in Exercise-Induced Cardiac Regeneration and Remodeling

Abstract

The non-cardiomyocyte cellular microenvironment of the heart includes diverse types of cells of mesenchymal origin. During development, the majority of these cells derive from the epicardium, while a subset derives from the endothelium/endocardium and neural crest derived mesenchyme. This subset includes cardiac fibroblasts and telocytes, the latter of which are a controversial type of "connecting cell" that support resident cardiac progenitors in the postnatal heart. Smooth muscle cells, pericytes, and endothelial cells are also present, in addition to adipocytes, which accumulate as epicardial adipose connective tissue. Furthermore, the heart harbors many cells of hematopoietic origin, such as mast cells, macrophages, and other immune cell populations. Most of these control immune reactions and inflammation. All of the above-mentioned non-cardiomyocyte cells of the heart contribute to this organ's well-orchestrated physiology. These cells also contribute to regeneration as a result of injury or age, in addition to tissue remodeling triggered by chronic disease or increased physical activity (exercise-induced cardiac growth). These processes in the heart, the most important vital organ in the human body, are not only fascinating from a scientific standpoint, but they are also clinically important. It is well-known that regular exercise can help prevent many cardiovascular diseases. However, the precise mechanisms underpinning myocardial remodeling triggered by physical activity are still unknown. Surprisingly, exercise-induced adaptation mechanisms are often identical or very similar to tissue remodeling caused by pathological conditions, such as hypertension, cardiac hypertrophy, and cardiac fibrosis. This review provides a summary of our current knowledge regarding the cardiac cellular microenvironment, focusing on the clinical applications this information to the study of heart remodeling during regular physical exercise.

Myocardial Telocyte-Like Cells: A Review Including New Evidence

“…Suciu et al [2010] studied telopode dynamics using time-lapse video microscopy, although they did not use any markers to achieve a positive distinction. Therefore, cardiac TCs were considered to be "a controversial DOI: 10.1159/000497194 type of connecting cell" [Varga et al, 2017b]. During different studies concerning TCs, care was taken to distinguish them from fibroblasts [Ibba-Manneschi et al, 2016] but not from other cell types, such as endothelial, vascular, and lymphatic cells, or from pericytes.…”

The Roles of Noncardiomyocytes in Cardiac Remodeling

“…The data showed that 55 fetal genes were expressed in LAD-ligated hearts; the downregulated genes included Nbl1, Myoz2, Lbh, Gfra1, Gpx3 and Efemp , while the upregulated genes were Tnc, Anp32b, Thy1, Lpar4 and Car3 132 . ECs participate in controlling CM contraction function as well as wound healing after pathological stress by secreting various biologically active substances, such as adhesion molecules (ICAM-1 and tenascin-C), pro-fibrotic cytokines (endothelin-1, Ang II, TGFβ1, periostin, and connective tissue growth factor), pro-inflammatory mediators (IL-6 and IL-1β), pro-angiogenetic factors (VEGF, PLGF, PDGF, bFGF, EGF, and HGF), cardioprotective mediators (follistatin-like 1, IGF-1, dickkopf-3, apelin, and LIF), some CXC chemokines, and other effectors 133 - 135 .…”

Follistatin‐like 1: A dual regulator that promotes cardiomyocyte proliferation and fibrosis

“…However, recent studies show that moderate exercise is an effective measure to prevent and treat cardiovascular diseases (Achttien et al, 2015). It is clear that exercise can upregulate FSTL1 levels to promote cardiomyocyte proliferation, and the mechanism by which exercise promotes cardiovascular health may be related to exercise‐induced cardiomyocyte proliferation (Bei et al, 2017; Varga, Kyselovic, Galfiova, & Danisovic, 2017). This may be the protective effect of exercise on heart and the mechanism of stress repair (Shen et al, 2017).…”