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

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fibrosis. This review provides a summary of our current knowledge regarding the

cardiac cellular microenvironment, focusing on the clinical applications this infor-

mation to the study of heart remodeling during regular physical exercise.

Keywords Non-cardiomyocyte Cells • Exercise • Regeneration • Remodeling

1 Introduction

Regeneration of tissues damaged by wear and tear or injury, in addition to tissue

remodeling as a result of chronic disease or increased physical activity, modify tis-

sue architecture through coordinated cell proliferation, differentiation, dedifferen-

tiation, and apoptosis [ 1 ]. These processes in the heart, the most important vital

organ in the human body, are not only a fascinating scientific problem, but they are

also clinically important. Surprisingly, cardiomyocytes account for only 25–35% of

all the cells in the heart. In fact, in the heart, morphologically and functionally dis-

tinct cardiac non-myocyte cells (all cells of the heart excluding cardiomyocytes)

constitute the majority of cells in this organ [ 2 ]. Non-cardiomyocytes are a diverse

group of cells and include fibroblasts, telocytes, mast cells, endothelial cells, white

blood cells, and other immunologically active cells, such as smooth muscle cells,

adipocytes, and pericytes. Exercise is a well-established intervention for the preven-

tion and treatment of cardiovascular diseases. The increase in the size of cardiomyo-

cytes is likely a central mechanism for exercise-induced cardiac growth, but other

cardiac cell types also respond to exercise. Therefore, exercise-induced cardiac

growth is a complex process that depends upon cross-talk between cardiomyocytes

and non-cardiomyocyte cells of the heart [ 3 ].

This review summarizes our current understanding of the cardiac cellular micro-

environment. It also discusses how this research might be applied to help develop

clinical treatments that promote heart regeneration and tissue remodeling. Expanding

our knowledge of the diverse non-myocyte cell populations present in the heart is

essential for understanding cardiac homeostasis during normal and pathological

conditions. Here, we focus on exercise-induced cardiac remodeling.

2 Cardiac Fibroblasts and Myofibroblasts

Fibroblasts are the most abundant cells in connective tissue. They produce all com-

ponents of the extracellular matrix, including protein fibers and amorphous ground

substance. They are also essential during wound healing.

Cardiac fibroblasts have been found in all compartments of the heart. They are

mainly responsible for the production of major components of the extracellular

matrix, including collagen (type I, III, V, and VI), periostin, vimentin, and fibronec-

tin. Thus, fibroblasts create a basic microenvironment for other cell types in the

I. Varga et al.