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Origin of Developmental Precursors Dictates the Pathophysiologic Role of Cardiac Fibroblasts

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Abstract

Fibroblasts in the heart play a critical function in the secretion and modulation of extracellular matrix critical for optimal cellular architecture and mechanical stability required for its mechanical function. Fibroblasts are also intimately involved in both adaptive and nonadaptive responses to cardiac injury. Fibroblasts provide the elaboration of extracellular matrix and, as myofibroblasts, are responsible for cross-linking this matrix to form a mechanically stable scar after myocardial infarction. By contrast, during heart failure, fibroblasts secrete extracellular matrix, which manifests itself as excessive interstitial fibrosis that may mechanically limit cardiac function and distort cardiac architecture (adverse remodeling). This review examines the hypothesis that fibroblasts mediating scar formation and fibroblasts mediating interstitial fibrosis arise from different cellular precursors and in response to different autocoidal signaling cascades. We demonstrate that fibroblasts which generate scars arise from endogenous mesenchymal stem cells, whereas those mediating adverse remodeling are of myeloid origin and represent immunoinflammatory dysregulation.

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Acknowledgments

This work is supported by National Institutes of Health RO1 HL-089792 (MLE), the American Heart Association 10SDG4280031 (SBH), the Hankamer Foundation, and the Medallion Foundation. The authors wish to thank Ms. Sharon Malinowski for her editorial assistance with the manuscript.

Ethical Considerations

The Guide for the Care and Use of Animals was followed when performing the experiments described in this paper. The experiments performed comply with the current laws of the country in which they were performed.

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Authors and Affiliations

  1. Baylor College of Medicine, One Baylor Plaza, M.S. BCM620, Houston, TX, 77030, USA

    Jeffrey R. Crawford, Sandra B. Haudek, Katarzyna A. Cieslik, JoAnn Trial & Mark L. Entman

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  1. Jeffrey R. Crawford
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  2. Sandra B. Haudek
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  3. Katarzyna A. Cieslik
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Correspondence to Mark L. Entman.

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Crawford, J.R., Haudek, S.B., Cieslik, K.A. et al. Origin of Developmental Precursors Dictates the Pathophysiologic Role of Cardiac Fibroblasts. J. of Cardiovasc. Trans. Res. 5, 749–759 (2012). https://doi.org/10.1007/s12265-012-9402-7

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