ABSTRACT
The diversity of cell types in the myocardium offers a complex context for the intricate and highly coordinated cell-cell and cell-environment interactions that are necessary for regenerative processes. The population of cells in the myocardium includes cardiac myocytes, endothelial cells, smooth muscle cells and cardiac fibroblasts. Cardiac fibroblasts play a central and multifaceted role in cardiac regeneration that is characterized by their trophic and protective effects on the one hand and their phenotypic plasticity on the other. The environmental factors necessary for muscle and vascular regeneration include extracellular matrix and an array of soluble factors consisting of matrix metalloproteases, cytokines and diverse growth factors necessary for cell growth and differentiation. Because cardiac fibroblasts constitute the majority of nonmyocyte cells in the heart1,2 theyare the principalsource of the extracellular matrix and soluble factors1-7 (Figure6.1). Most importantly, the demonstrated resilience of cardiac fibroblasts under environmental stress, including hypoxia and hypothermia, enhances their potential to influence muscle and vascular regeneration in response to pathophysiologic stimuli during development, normal growth, aging, ventricular hypertrophy and heart failure after myocardial infarction. As the result of their proven phenotypic plasticity and their predisposition to transform into cells with features characteristic of myocytes, cardiac fibroblasts can directly enter into myogenic pathways and contribute to the regeneration of cardiac muscle. This chapter is aimed at providing insights into the mechanisms by which cardiac fibroblasts may regulate various aspects of muscle and vascular regeneration in the heart. Specifically, the role of the extracellular matrix and soluble factors and the effects brought about as the result of the phenotypic plasticity of cardiac fibroblasts will be discussed (Figure 6.2).
