Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease

Myocardium is comprised of a number of cell types, cardiomyocytes, cardiofibroblasts, endothelial cells and smooth muscle cells. Cardiac fibroblasts (CFBs) have the highest cell population in the myocardium, accounting for about two-thirds of the cells, while cardiomyocytes constitute about two-thirds of the myocardial tissue volume [1], although this ratio may vary in different species [2]. A number of excellent reviews have discussed the contribution of the contractile proteins and the molecules involved in intracellular calcium handing in cardiomyocytes in cardiac pathologies [3-5]. In this review, we will provide an overview of the literature on the role of CFBs in the context of extracellular matrix (ECM) remodeling and its contribution to development and progression of heart disease. Fibroblasts (FBs) are cells of mesenchymal origin and are present in every tissue in the body [2,6]. Morphologically, FBs are flat and spindle-shaped with multiple projecting processes. In the myocardium, CFBs are unique among other cell types in that they lack a basement membrane. Although historically FBs were considered a homogeneous cell population, it has become increasingly clear that FBs from different tissues have different properties and functions [2,7]. In this review we will focus our discussion on CFBs, although some of the discussed properties and functions could also apply to FBs from other tissue sources.A number of cell surface markers have been identified for FBs and CFBs, but over time their specificity to these cells has been challenged. Vimentin, a protein that is present in the intermediate filaments of FBs, has been the most widely used FB marker – and although it is also expressed in other cell types such as endothelial cells [8] and myoepithelial cells [9], due to morphological differences among these cell types, vimentin remains a reliable marker for identifying FBs [10]. Discoidin domain receptor (DDR) 2 was discovered as a specific marker for CFBs [1,2,1