Exercise for Cardiovascular Disease Prevention and Treatment From Molecular to Clinical, Part 1

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Telocytes are known to be present in or near stem cell niches in various human

organs. This includes the subepicardial cardiac layer [ 48 – 50 ]. In this tissue layer,

cardiac stem cell niches harboring cardiomyocyte progenitors are found surround-

ing the coronary arteries [ 51 ]. Each niche contains cardiac progenitors in various

stages of differentiation, in addition to loose connective tissue that harbors mast

cells, adipocytes, macrophages, fibroblasts, a rich capillary bed, telocytes, and nerve

fibers [ 48 ]. Recent in vitro studies suggest that the telopodes of telocytes form com-

plex scaffolds that are required to organize the myocardium during tissue regenera-

tion [ 49 ]. Furthermore, telocytes are often referred to as “nurse cells” for cardiac

stem cells because they aid the differentiation and integration of stem cell progeni-

tors into the developing or regenerating heart [ 50 ].

A few studies have investigated the contribution of telocytes to the etiology of

cardiac diseases. Richter and Kostin [ 52 ] demonstrated that there is a reduction in the

abundance of cardiac telocytes in patients suffering from end-stage heart failure fol-

lowing transplantation. The loss of telocytes also occurred in rats following myocar-

dial infarction [ 53 ]. In subsequent weeks of observation of these rats, cardiac telocytes

also failed to migrate into the damaged heart tissue from nearby healthy myocar-

dium, which likely inhibited regeneration of the affected myocardium. Thus, telo-

cytes may contribute to neoangiogenesis following a myocardial infarction [ 54 ].

Interestingly, when cardiac telocytes were transplanted into sites of myocardial

infarction in rats a reduction in the size of damaged tissue was observed. The animals

also experienced significant improvements in heart function. It is therefore possible

that the transplantation of healthy cardiac telocytes might increase overall vessel den-

sity and decrease myocardial fibrosis in hearts following an infarction [ 53 ]. Future

cell-based therapeutic approaches of this nature might enhance cardiac regeneration,

repair, and protection in patients suffering from various heart diseases [ 55 , 56 ].

We are aware of only one report linking cardiac telocyte activity to physical exercise.

Xiao et al. [ 57 ] used a ramp swimming exercise to study the connection between cardiac

telocytes function and exercise-induced cardiac growth in mice. It was shown that the

number of telocytes increased significantly in the heart following exercise, suggesting

that this cell population might modulate the physiology of cardiac stem cells, cardiomyo-

cytes, and/or other endothelial cells. This lends further support to the idea that cardiac

telocytes likely enhance cardiac regeneration following an injury or aging processes.

4 Cardiac Adipocytes and Epicardial Adipose Tissue

Adipose cells (fat cells, adipocytes) are specialized cells of the connective tissue

that synthesize and store lipids as an energy reserve. Currently, white adipose tissue

is considered to not only be an energy-storing organ, but it also acts as:

• an active endocrine organ with an intricate role in systemic homeostasis [ 58 ],


• a reservoir for a high number of adipose-tissue derived mesenchymal stem cells [ 59 ],


• a regulator of immune responses (e.g., obesity, which is associated with low- grade,

sustained, and systemic inflammation, termed obesity-related inflammation) [ 60 ].

8 The Non-cardiomyocyte Cells of the Heart. Their Possible Roles...