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

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the origin of macrophages. The traditional model states that blood monocytes give


rise to all tissue macrophages. The second hypothesis assumes a prenatal coloniza-


tion of tissues by resident macrophages derived from embryonic yolk sac progeni-


tors. These macrophages persist throughout adulthood and self-renew without input


from circulating monocytes [ 93 – 95 ].


Macrophages secrete a variety of cytokines, pro-inflammatory molecules, and

trophic mediators. Some of these have been suggested to inhibit apoptosis in


hypoxic cardiomyocytes or promote neonatal heart regeneration [ 96 ]. In various


cardiac diseases, such as ischemic heart disease and idiopathic dilated cardiomy-


opathy, the expansion of macrophage populations occurs [ 97 ]. Cardiac macrophages


may contribute to tissue remodeling during chronic pressure-overload heart failure


or heart fibrosis through the activation of myofibroblasts [ 98 , 99 ]. The role of mac-


rophages in inflammation after a myocardial infarct indicates that these cells are


absolutely necessary for adequate wound healing and scar formation [ 100 ].


There is only one scientific article that describes the link between cardiac macro-

phages and physical exercise. In a study by Botta et al. [ 101 ], the infiltration of the


hearts of diabetic mice by F4/80+ macrophages was attenuated by exercise, which


consisted of animals running on a motorized exercise wheel system.


7 Cardiac Endothelial Cells and Pericytes


Endothelial cells resemble simple squamous epithelial cells. They have their own


basal lamina and line blood vessels. The internationally accepted Terminologia


Histologica describes them as an epithelial tissue [ 38 ]. On the other hand, they are


of mesodermal origin and can produce collagen type IV. Therefore, endothelial cells


are also considered to be connective tissue cells. Inside the heart, there are two dif-


ferent populations of cardiac endothelial cells:



  • vascular endothelium (lining the luminal surface of the coronary vessels; Fig. 8.8)

  • endocardial endothelium (a continuous monolayer of cells that line the cavities


of the heart; Fig. 8.9).

The differences between these types of endothelial cells are apparent only on the

ultrastructural level. For example, endocardial endothelial cells have Weibel-Palade


bodies in their cytoplasm, which contain von Willebrand factor [ 102 ]. Additionally,


endocardial endothelium has a different cell shape, cytoskeletal organization, and


permeability than vascular endothelium [ 103 ]. From an embryological point of


view, vascular endothelium originates from the epicardium, and endocardial endo-


thelium originates from the cardiogenic plate [ 104 ].


Both vascular and endocardial endothelial cells play a role in controlling the

contractility of cardiomyocytes by releasing various biologically active autocrine


and paracrine agents. Cardiac endothelial cells produce nitric oxide, endothelin-1,


prostaglandin I (2), angiotensin II, and other factors [ 104 , 105 ]. All of these sub-


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

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