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Fibroblast Activation in the Infarcted Myocardium

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Cardiac Fibrosis and Heart Failure: Cause or Effect?

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 13))

Abstract

The adult mammalian heart contains abundant fibroblasts. Cardiac fibroblasts are versatile and dynamic cells that not only produce extracellular matrix proteins, but may also serve important functions in myocardial inflammation, angiogenesis and repair. Following injury, cardiac fibroblasts may maintain the integrity of the extracellular matrix network preserving cardiac geometry and function. Myocardial infarction induces dynamic alterations in fibroblast phenotype. During the early stages of infarct healing, cardiac fibroblasts may serve as sentinel cells that sense signals released by dying cardiomyocytes and activate the inflammasome, secreting cytokines and chemokines. During the inflammatory phase, fibroblasts exhibit a matrix-degrading phenotype; myofibroblast conversion may be delayed by activation of Interleukin-1 (IL-1) signaling. Suppression of pro-inflammatory signals and termination of IL-1-driven cascades during the proliferative phase of infarct healing may allow unopposed actions of Transforming Growth Factor (TGF)-β on cardiac fibroblasts, mediating myofibroblast transdifferentiation, matrix synthesis and scar contraction. Angiotensin II, the mast cell proteases chymase and tryptase, growth factors and specialized matrix proteins may co-operate to promote a synthetic and proliferative myofibroblast phenotype. The maturation phase follows, as infarct myofibroblasts cross-link the surrounding matrix, become quiescent and may undergo apoptosis. However, in the non-infarcted remodeling myocardium, fibroblasts may remain activated in response to volume and pressure overload promoting interstitial fibrosis. This chapter discusses the role of cardiac fibroblasts in infarct healing and the mechanisms of their activation, suggesting potential therapeutic targets aimed at attenuating adverse post-infarction remodeling.

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Acknowledgments

Dr Frangogiannis’ laboratory is supported by NIH grants R01 HL76246 and R01 HL85440.

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Authors and Affiliations

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

    Amit Saxena & Nikolaos G. Frangogiannis MD

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  1. Amit Saxena
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  2. Nikolaos G. Frangogiannis MD
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Correspondence to Nikolaos G. Frangogiannis MD .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface Hospital Research Centre Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada

    Ian M.C. Dixon

  2. Institute of Cardiovascular Sciences St. Boniface Hospital Research Centre Department of Biochemistry and Medical Genetics, University of Manitoba, Winnipeg, Canada

    Jeffrey T. Wigle

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© 2015 Springer International Publishing Switzerland

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Saxena, A., Frangogiannis, N. (2015). Fibroblast Activation in the Infarcted Myocardium. In: Dixon, I., Wigle, J. (eds) Cardiac Fibrosis and Heart Failure: Cause or Effect?. Advances in Biochemistry in Health and Disease, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-17437-2_2

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