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

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many other types of cells and, thus, are not mast cell-specific [ 80 ]. For example,

CD117 is frequently used to identify not only mast cells, but also cardiac muscle

progenitor cells [ 81 ] and telocytes [ 82 ].

Cardiac mast cells are frequently localized in close proximity to blood vessels.

This suggests that circulating antigens or drugs used during disease treatment or

diagnostic procedures can easily reach these cardiac mast cells [ 79 ]. Mast cells store

and release a variety of biologically and pharmacologically active mediators. Some

of these, such as histamine, heparin, and serine proteases (tryptase and chymase),

are stored in cytoplasmic granules. Other vasoactive and cell signaling mediators,

such as leukotriens, interleukins, and prostaglandin D2, are released from the cell

membrane during mast cell activation [ 83 ]. Furthermore, cardiac mast cells contain

and release renin, which initiates local angiotensin formation. This may result in

coronary vasoconstriction, arrhythmias, and fibrosis [ 84 ].

In general, cardiac mast cells are responsible for immune reactions and inflam-

mation. Mast cells manufacture a wide variety of proteases, cytokines, growth fac-

tors, and vasoactive substances that may influence myocardial remodeling [ 85 ].

Mast cell proteases are capable of activating collagenase, and other mediators, such

as tryptase and chymase, have the ability to activate metalloproteinases [ 86 ]. In

recent years, numerous interesting studies have been published that focused on the

role of cardiac mast cells during the pathogenesis of cardiac diseases (mostly in

animal models). For example, Levick et al. [ 87 ] demonstrated a causal relationship

between cardiac mast cells and the development of left ventricular fibrosis in

response to hypertension. A significant increase in cardiac mast cell density was

also observed to correlate with cardiac hypertrophy and heart failure. For these rea-

sons, mast cells may contribute to the development of cardiac hypertrophy and heart

failure [ 88 ]. Finally, mast cells may play a role in the etiology of eosinophilic coro-

nary periarteritis, a rare eosinophil-induced inflammation associated with spontane-

ous coronary artery dissection and sudden cardiac death [ 89 ].

The activity of mast cells can be modulated be exercise. In a rat model, for exam-

ple, Phungphong et al. [ 90 ] found that regular exercise had a protective effect on the

heart by inhibiting the degranulation of mast cells.

6 Cardiac Mononuclear Phagocytic Cells

In general, cardiac immune cells are gaining interest for the roles they play in patho-

logical remodeling in a number of cardiac diseases [ 91 ]. These immune cells include

T-lymphocytes and macrophages. B-lymphocytes are less numerous in the human

myocardium [ 92 ].

Macrophages belong to the mononuclear phagocytic system and are part of the

innate immune system. They play a role in the maintenance of normal tissues by

ingesting dead cells and cellular debris and breaking them down with lysosomal

enzymes. Macrophages participate in the immunological response. They are the first

line of defense against infection. There are two predominant hypotheses regarding

I. Varga et al.