Cardiac Fibrosis: The Fibroblast Awakens

Cardiac Fibrosis: The Fibroblast Awakens

Joshua G. Travers, Fadia A. Kamal, Jeffrey Robbins, Katherine E. Yutzey, Burns C. Blaxall

Proposed sources of cardiac myofibroblasts. The source(s) of activated cardiac fibroblasts that accumulate in response to various pathological insults remains under active investigation. Mounting evidence suggests that activated myofibroblasts in the fibrotic heart derive from the proliferation and activation of resident fibroblasts, as these cells are remarkably sensitive to pathological insult and represent a feasible source of matrix-producing cells during cardiac fibrosis. Numerous additional precursors to the fibroblast population in the injured heart have been proposed; these include endothelial and epicardial cells, through epithelial–mesenchymal transition and endothelial–mesenchymal transition, respectively, hematopoietic bone marrow–derived cells, perivascular cells, and fibrocytes. Although supporting evidence exists for cellular sources of activated fibroblasts denoted by question marks, controversy remains about the functional contribution of these cell types to the cardiac myofibroblast population. Biomarkers with greater specificity will be required to fully characterize the pathophysiological relevance of these cell types in the cardiac fibrotic response, which will enable potential targeting for antifibrotic therapies. [Powerpoint File]

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