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Decreased TGF-β1 and VEGF Release in Cystic Fibrosis Platelets: Further Evidence for Platelet Defects in Cystic Fibrosis

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Abstract

Purpose

Cystic fibrosis (CF) patients suffer from chronic lung inflammation. This inflammation may activate platelets. There are limited data on the role of platelet-secreted cytokines in CF. Platelet cytokines with inflammatory effects include vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1). As levels of these cytokines are tenfold greater in serum than plasma due to platelet release, serum levels may be one index of platelet content, but a more specific index is release during the aggregation of isolated platelets. We postulated that altered release of these platelet cytokines occurs in CF.

Methods

We obtained sera and plasma from CF outpatients (n = 21) and from healthy controls (n = 20), measured VEGF and TGF-β1, assessed for correlations with platelet number, analyzed cytokine release during platelet aggregation to collagen, and analyzed differences in maximal platelet aggregation.

Results

Platelet number and maximal aggregation levels were higher in CF. Plasma and serum levels of TGF-β1 and VEGF were higher in CF, but these levels were similar after adjusting for platelet number (serum cytokines correlated with platelet count). The release of VEGF and TGF-β1 during aggregation was decreased in CF platelets (by 52 and 29 %, respectively).

Conclusion

Platelet release is not a source of the elevated blood proinflammatory cytokines TGF-β1 and VEGF in CF, as platelets from CF patients actually release less of these cytokines. These data provide further evidence for platelet defects in CF.

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Abbreviations

CF:

Cystic fibrosis

CFTR:

Cystic fibrosis transmembrane conductance regulator

NSAID:

Nonsteroidal anti-inflammatory drug

PRP:

Platelet-rich plasma

PPP:

Platelet-poor plasma

TGF-β1 :

Transforming growth factor-beta 1

VEGF:

Vascular endothelial growth factor

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Acknowledgments

We thank the cystic fibrosis patients and healthy subjects who volunteered for this study. This work was supported by Grant K08 HL035454 from the United States National Institutes of Health, National Heart Lung, and Blood Institute (JM).

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Authors and Affiliations

  1. Divisions of Pulmonary and Critical Care Medicine, University of Colorado, Denver, 12700 East 19th Avenue, C-272, Aurora, Denver, CO, 80045, USA

    James P. Maloney

  2. Apollo Hospitals, Chennai, India

    Jayashree Narasimhan

  3. The Medical College of Wisconsin, Milwaukee, WI, USA

    Julie Biller

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  1. James P. Maloney
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  2. Jayashree Narasimhan
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  3. Julie Biller
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Correspondence to James P. Maloney.

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Maloney, J.P., Narasimhan, J. & Biller, J. Decreased TGF-β1 and VEGF Release in Cystic Fibrosis Platelets: Further Evidence for Platelet Defects in Cystic Fibrosis. Lung 194, 791–798 (2016). https://doi.org/10.1007/s00408-016-9925-9

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  • DOI: https://doi.org/10.1007/s00408-016-9925-9

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