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

Lung. 2016 Oct;194(5):791-8. doi: 10.1007/s00408-016-9925-9. Epub 2016 Jul 16.

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.

Keywords: Cystic fibrosis; Platelet aggregation; Platelets; Transforming growth factor-β; Vascular endothelial growth factor.

MeSH terms

  • Adult
  • Blood Platelets / metabolism*
  • Case-Control Studies
  • Cystic Fibrosis / blood*
  • Female
  • Humans
  • Male
  • Plasma / metabolism*
  • Platelet Aggregation
  • Platelet Count
  • Serum / metabolism*
  • Transforming Growth Factor beta1 / blood*
  • Vascular Endothelial Growth Factor A / blood*

Substances

  • Transforming Growth Factor beta1
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A