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

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Another major function of cardiac fibroblasts is to express different growth fac-

tors, cytokines, and other bioactive molecules. These factors exert autocrine and

paracrine effects on the cardiac cells and, thus, promote their proliferation, contrac-

tion, and apoptosis [ 24 ].

Recent studies demonstrated that cardiac fibroblasts play critical roles in electri-

cal signaling because they possess a high membrane resistance, which makes them

excellent conductors. It was shown that fibroblasts are physically coupled to other

cells of the myocardium, including myocytes. The cell junctions forming these con-

nections are composed mainly of connexins CX40, CX43, and CX45 [ 25 , 26 ].

Some studies indicate that cardiac fibroblasts act as bridges connecting myocytes

that are normally electrically isolated by connective tissues [ 27 ].

Lastly, cardiac fibroblasts have an important role in angiogenesis. They affect

this process by releasing several growth factors, such as fibroblast growth factor,

vascular endothelial growth factor, and pigment epithelium-derived growth factor

[ 28 , 29 ].

3 Cardiac Telocytes

A telocyte is a type of connecting cell found in various organs in the human body.

This includes the heart, which contains telocytes in all cardiac tissue layers.

Telocytes create a cellular meshwork throughout the epicardium, endocardium, and

myocardium. They can even be found in cardiac stem cell niches [ 30 , 31 ]. They tend

to have a small, rounded appearance, and can sometimes have a spindle-shaped cell

body. Most display extremely long cytoplasmic protrusions called telopodes. Each

telocyte sprouts 2–5 telopodes, and each of the prolongations can range from doz-

ens to hundreds of micrometers in length with an average thickness of 0.2 μm. Many

telopodes form secondary and tertiary branching patterns, and this is what creates

the three-dimensional network characteristic of cardiac telocytes. These networks

envelop capillaries and connect neighboring telocytes with other tissue types in the

heart [ 32 ]. Because telopodes are very thin cellular structures, telocytes and their

networks must be visualized by transmission electron microscopy (Fig. 8.1) [ 33 , 34 ]

or immunohistochemical staining (Fig. 8.2). Several different antigens are expressed

in telocytes, including CD34, CD117 (c-kit), vimentin, and PDGF receptor-alpha

and receptor-beta. Unfortunately, all these antigens are also enriched in other non-

telocyte cell types. For example, mast cells also express CD117. Therefore, research-

ers typically use a double-immunolabeling approach to distinguish telocytes from

other interstitial cells. Telocytes are often defined as CD34+/vimentin+, CD34+/

PDGFR-beta+, or CD34+/CD117+ cells, effectively differentiating them from car-

diac fibroblasts [ 35 , 36 ]. Unfortunately, telocytes cannot currently be distinguished

during embryonic development because the maturing progenitors are negative for

both CD117 and CD34 [ 37 ].

Telocytes are not typically recognized as a distinct cell population. Although the

term “telocytes” yields over 240 references in PubMed, there are no official entries

I. Varga et al.