The origin of fibroblasts and mechanism of cardiac fibrosis

Abstract

Fibroblasts are at the heart of cardiac function and are the principal determinants of cardiac fibrosis. Nevertheless, cardiac fibroblasts remain poorly characterized in molecular terms. Evidence is evolving that the cardiac fibroblast is a highly heterogenic cell population, and that such heterogeneity is caused by the distinct origins of fibroblasts in the heart. Cardiac fibroblasts can derive either from resident fibroblasts, from endothelial cells via an endothelial-mesenchynmal transition or from bone marrow-derived circulating progenitor cells, monocytes and fibrocytes. Here, we review the function and origin of fibroblasts in cardiac fibrosis.NB. The information given is correct.

Fig. 1

Sources of cardiac fibroblasts. In the developing embryo, cardiac fibroblast originate from the epithelial cells of the proepicardium through a process termed epithelial–mesenchymal transition (EMT). Valvular fibroblast arise through endothelial–mesenchymal transition (EndMT) of the endocardium. The development of fibroblast during cardiopathy involves considerably more cell plasticity, with the pro-fibrotic cells being derived from the endothelium and epithelium through mesenchymal transition (EMT and EndMT). Also fibroblast may be derived from perivascular cells, circulating monocytes and bone marrow-derived progenitor cells and circulating fibrocytes.

Fig. 2

Pleiotropic functions of cardiac fibroblasts. Cardiac fibroblasts are at the heart of cardiac development and function. Cardiac fibroblasts are involved in the production and degradation of the cardiac extracellular matrix through the production of amongst others collagens, proteoglycans, matrix metalloproteinases and TIMPs. Additionally, cardiac fibroblasts secrete various bioactive mediators (e.g., VEGFa, FGFs, TGFβ, PDGF) which influence cardiac angiogenesis and myocyte proliferation. Furthermore, cardiac fibroblasts influence cardiac electrophysiology by insulating myocyte bundles, transmitting electrical signals, and converting mechanical stimuli into electronic signals.