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  • Review Article
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Fibroblasts orchestrate cellular crosstalk in the heart through the ECM

Nature Cardiovascular Research volume 1, pages 312–321 (2022)Cite this article

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Abstract

Cell communication is needed for organ function and stress responses, especially in the heart. Cardiac fibroblasts, cardiomyocytes, immune cells and endothelial cells comprise the major cell types in the ventricular myocardium that together coordinate all functional processes. Critical to this cellular network is the non-cellular extracellular matrix (ECM) that provides structure and harbors growth factors and other signaling proteins that affect cell behavior. The ECM not only is produced and modified by cells within the myocardium, largely cardiac fibroblasts, but also acts as an avenue for communication among all myocardial cells. In this Review, we discuss how the development of therapeutics to combat cardiac diseases, specifically fibrosis, relies on a deeper understanding of how the cardiac ECM is intertwined with signaling processes that underlie cellular activation and behavior.

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Fig. 1: The ECM facilitates communication among fibroblasts, cardiomyocytes and macrophages in the heart.
Fig. 2: Cardiomyocytes and fibroblasts sense each other through the dynamic ECM environment.
Fig. 3: Promising therapeutic targets for mediating CF activation and fibrosis.

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Acknowledgements

We acknowledge the researchers and studies that have contributed to our knowledge of cardiac development and fibrosis but were not discussed here due to space and reference limitations. This work was supported by grants from the NIH (R01HL105924 and R01HL142217) to J.D.M. and a Career Development award from the American Heart Association (20CDA35310504) to Q.M.

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  1. These authors contributed equally: Stephanie L. K. Bowers, Qinghang Meng.

Authors and Affiliations

  1. Division of Molecular Cardiovascular Biology, Cincinnati Children’s Hospital, Cincinnati, OH, USA

    Stephanie L. K. Bowers, Qinghang Meng & Jeffery D. Molkentin

  2. Department of Pediatrics, University of Cincinnati, Cincinnati, OH, USA

    Stephanie L. K. Bowers, Qinghang Meng & Jeffery D. Molkentin

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S.L.K.B., Q.M. and J.D.M wrote or edited the manuscript.

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Bowers, S.L.K., Meng, Q. & Molkentin, J.D. Fibroblasts orchestrate cellular crosstalk in the heart through the ECM. Nat Cardiovasc Res 1, 312–321 (2022). https://doi.org/10.1038/s44161-022-00043-7

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