TY - JOUR
T1 - The extracellular matrix modulates fibroblast phenotype and function in the infarcted myocardium
AU - Dobaczewski, Marcin
AU - De Haan, Judith J.
AU - Frangogiannis, Nikolaos G.
N1 - Funding Information:
Acknowledgments Dr. Frangogiannis’ laboratory is supported by NIH grants R01 HL-76246 and HL-85440, the Wilf Family Cardiovascular Research Institute, and the Edmond J Safra/Republic National Bank of New York Chair in Cardiovascular Medicine.
PY - 2012/12
Y1 - 2012/12
N2 - Cardiac fibroblasts are key cellular effectors of cardiac repair; their phenotype and function are modulated by interactions with extracellular matrix proteins. This review manuscript discusses the effects of the extracellular matrix on the inflammatory and reparative properties of fibroblasts in the infarcted myocardium. Early generation of matrix fragments in the infarct induces a pro-inflammatory and matrix-degrading fibroblast phenotype. Formation of a fibrin/fibronectin-rich provisional matrix serves as a conduit for migration of fibroblasts into the infarcted area. Induction of ED-A fibronectin and nonfibrillar collagens may contribute to myofibroblast transdifferentiation. Upregulation of matricellular proteins promotes transduction of growth factor and cytokine-mediated signals. As the scar matures, matrix cross-linking, clearance of matricellular proteins, and reduced growth factor signaling cause deactivation and apoptosis of reparative infarct fibroblasts. Understanding the effects of matrix components on infarct fibroblasts may guide the design of peptides that reproduce, or inhibit, specific matricellular functions, attenuating adverse remodeling.
AB - Cardiac fibroblasts are key cellular effectors of cardiac repair; their phenotype and function are modulated by interactions with extracellular matrix proteins. This review manuscript discusses the effects of the extracellular matrix on the inflammatory and reparative properties of fibroblasts in the infarcted myocardium. Early generation of matrix fragments in the infarct induces a pro-inflammatory and matrix-degrading fibroblast phenotype. Formation of a fibrin/fibronectin-rich provisional matrix serves as a conduit for migration of fibroblasts into the infarcted area. Induction of ED-A fibronectin and nonfibrillar collagens may contribute to myofibroblast transdifferentiation. Upregulation of matricellular proteins promotes transduction of growth factor and cytokine-mediated signals. As the scar matures, matrix cross-linking, clearance of matricellular proteins, and reduced growth factor signaling cause deactivation and apoptosis of reparative infarct fibroblasts. Understanding the effects of matrix components on infarct fibroblasts may guide the design of peptides that reproduce, or inhibit, specific matricellular functions, attenuating adverse remodeling.
KW - Cardiac remodeling
KW - Extracellular matrix
KW - Fibroblast
KW - Matricellular proteins
KW - Myocardial infarction
KW - Myofibroblast
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U2 - 10.1007/s12265-012-9406-3
DO - 10.1007/s12265-012-9406-3
M3 - Article
C2 - 22956156
AN - SCOPUS:84878183269
SN - 1937-5387
VL - 5
SP - 837
EP - 847
JO - Journal of Cardiovascular Translational Research
JF - Journal of Cardiovascular Translational Research
IS - 6
ER -