Expansion and activation of fibroblasts following cardiac injury is important for repair but may also contribute to fibrosis, remodeling, and dysfunction. The authors discuss the dynamic alterations of fibroblasts in failing and remodeling myocardium. Emerging concepts suggest that fibroblasts are not unidimensional cells that act exclusively by secreting extracellular matrix proteins, thus promoting fibrosis and diastolic dysfunction. In addition to their involvement in extracellular matrix expansion, activated fibroblasts may also exert protective actions, preserving the cardiac extracellular matrix, transducing survival signals to cardiomyocytes, and regulating inflammation and angiogenesis. The functional diversity of cardiac fibroblasts may reflect their phenotypic heterogeneity.
Keywords: AT1, angiotensin type 1; ECM, extracellular matrix; FAK, focal adhesion kinase; FGF, fibroblast growth factor; IL, interleukin; MAPK, mitogen-activated protein kinase; MRTF, myocardin-related transcription factor; PDGF, platelet-derived growth factor; RNA, ribonucleic acid; ROCK, Rho-associated coiled-coil containing kinase; ROS, reactive oxygen species; SMA, smooth muscle actin; TGF, transforming growth factor; TRP, transient receptor potential; cytokines; extracellular matrix; fibroblast; infarction; lncRNA, long noncoding ribonucleic acid; miRNA, micro–ribonucleic acid; remodeling.