Cardiomyocyte stress signaling and metabolic dysregulation act as upstream drivers of cardiac fibrosis through coordinated interactions with fibroblasts, immune cells, and endothelial cells.
Cardiac fibrosis is a central pathological feature of heart failure and contributes to myocardial stiffening, impaired electrical conduction, and progressive ventricular dysfunction. Traditionally, fibrotic remodeling has been viewed as a fibroblast-driven process in which activated fibroblasts deposit excessive extracellular matrix following cardiac injury. However, emerging evidence indicates that fibrosis arises from coordinated interactions among multiple cardiac cell populations, including cardiomyocytes, endothelial cells, immune cells, pericytes, and fibroblasts. In this review, we discuss the role of cardiomyocytes and their interactions with other cell types in the heart in facilitating cardiac fibrosis. We discuss how interactions among cardiomyocytes, immune cells, endothelial cells, pericytes, and fibroblasts contribute to fibrotic remodeling in both ischemic and non-ischemic heart disease. Our signaling emphasis is on transforming growth factor-β (TGF-β)-mediated cardiac fibrosis in the context of cellular interplay. We posit that a better understanding of these integrated signaling networks may reveal new opportunities to prevent or reverse pathological cardiac fibrosis.
Karthikeyan et al. (Thu,) conducted a review in Cardiac fibrosis. Cardiomyocyte stress signaling and metabolic dysregulation act as upstream drivers of cardiac fibrosis through coordinated interactions with fibroblasts, immune cells, and endothelial cells.