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The Extracellular Matrix Modulates Fibroblast Phenotype and Function in the Infarcted Myocardium

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Abstract

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.

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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.

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Authors and Affiliations

  1. Department of Medicine (Cardiology), The Wilf Family Cardiovascular Research Institute, Albert Einstein College of Medicine, 1300 Morris Park Avenue Forchheimer G46B, Bronx, NY, 10461, USA

    Marcin Dobaczewski, Judith J. de Haan & Nikolaos G. Frangogiannis

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  1. Marcin Dobaczewski
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  2. Judith J. de Haan
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  3. Nikolaos G. Frangogiannis
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Correspondence to Nikolaos G. Frangogiannis.

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Dobaczewski, M., de Haan, J.J. & Frangogiannis, N.G. The Extracellular Matrix Modulates Fibroblast Phenotype and Function in the Infarcted Myocardium. J. of Cardiovasc. Trans. Res. 5, 837–847 (2012). https://doi.org/10.1007/s12265-012-9406-3

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  • DOI: https://doi.org/10.1007/s12265-012-9406-3

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