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Cardiac fibroblasts support cardiac inflammation in heart failure

Basic Research in Cardiology volume 109, Article number: 428 (2014) Cite this article

Abstract

Cardiac remodeling and inflammation are hallmarks of cardiac failure and correlate with outcome in patients. However, the basis for the development of both remains unclear. We have previously reported that cardiac inflammation triggers transdifferentiation of fibroblasts to myofibroblasts and therefore increase accumulation of cardiac collagen, one key pathology in cardiac remodeling. Hence, identifying key pathways for inflammation would be beneficial for patients suffering from heart failure also. Besides their well-characterized function in matrix regulation, we here investigate the role of fibroblasts in the inflammatory process. We address for the first time the role of fibroblasts as inflammatory supporter cells in heart failure. Using endomyocardial biopsies from patients with heart failure and dilated cardiomyopathy, we created a primary human cardiac fibroblast cell culture system. We found that mechanical stretch mimicking cardiac dilation in heart failure induces activation of fibroblasts and not only stimulates production of extracellular matrix but more interestingly up-regulates chemokine production and triggers typical inflammatory pathways in vitro. Moreover, the cell culture supernatant of stretched fibroblasts activates inflammatory cells and induces further recruitment of monocytes by allowing transendothelial migration into the cardiac tissue. Our findings reveal that cardiac fibroblasts provide pro-inflammatory mediators and may act as sentinel cells activated by mechanical stress. Those cells are able to recruit inflammatory cells into the cardiac tissue, a process known to aggravate outcome of patients. This might be important in different forms of heart failure and therefore may be one general mechanism specific for fibroblasts.

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Acknowledgments

The present study was supported by the Deutsche Forschungsgemeinschaft (DFG, SFB-TR-19, TP A2) and by the Ernst und Berta Grimmke Stiftung. We thank Mareile Schröder, Nadine Orrin, Frauke Gotzhein, Katrin Hinz, Kerstin Puhl, and Georg Zingler for technical assistance.

Conflict of interest

None.

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Authors and Affiliations

  1. Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Martinistr. 52, 20246, Hamburg, Germany

    Diana Lindner, Nina Fluschnik, Svenja Hinrichs, Stefan Blankenberg & Dirk Westermann

  2. Department of Cardiology and Pneumology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin (CBF), Berlin, Germany

    Christin Zietsch, Juliane Tank, Wolfgang Poller, Heinz-Peter Schultheiss & Carsten Tschöpe

  3. Department of Cardiology and Pneumology/Herzzentrum, Georg-August-Universität Göttingen, Göttingen, Germany

    Samuel Sossalla

  4. DZHK (German Centre for Cardiovascular Research), Hamburg/Kiel/Luebeck, Germany

    Diana Lindner, Stefan Blankenberg & Dirk Westermann

  5. DZHK (German Centre for Cardiovascular Research), Berlin, Germany

    Heinz-Peter Schultheiss & Carsten Tschöpe

  6. DZHK (German Centre for Cardiovascular Research), Göttingen, Germany

    Samuel Sossalla

  7. Department of Internal Medicine II, University of Regensburg, Regensburg, Germany

    Lars Maier

Authors
  1. Diana Lindner
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  2. Christin Zietsch
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  3. Juliane Tank
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Correspondence to Diana Lindner or Dirk Westermann.

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Lindner, D., Zietsch, C., Tank, J. et al. Cardiac fibroblasts support cardiac inflammation in heart failure. Basic Res Cardiol 109, 428 (2014). https://doi.org/10.1007/s00395-014-0428-7

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  • DOI: https://doi.org/10.1007/s00395-014-0428-7

Keywords

  • Fibrosis
  • Fibroblast
  • Remodeling
  • Inflammation
  • Heart failure