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

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.