Platelet extracellular vesicles induce a pro-inflammatory smooth muscle cell phenotype

Tanja Vajen*, Birke J. Benedikter, Alexandra C. A. Heinzmann, Elena M. Vasina, Yvonne Henskens, Martin Parsons, Patricia B. Maguire, Frank R. Stassen, Johan W. M. Heemskerk, Leon J. Schurgers, Rory R. Koenen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

60 Citations (Web of Science)

Abstract

Extracellular vesicles (EVs) are mediators of cell communication during health and disease, and abundantly released by platelets upon activation or during ageing. Platelet EVs exert modulatory effects on immune and vascular cells. Platelet EVs may modulate the function of vascular smooth muscle cells (SMC). Platelet EVs were isolated from platelet-rich plasma and incubated with SMC in order to assess binding, proliferation, migration and pro-inflammatory phenotype of the cells. Platelet EVs firmly bound to resting SMC through the platelet integrin a(11b)beta(3), while binding also occurred in a CX3CL1-CX3CR1-dependent manner after cytokine stimulation. Platelet EVs increased SMC migration comparable to platelet derived growth factor or platelet factor 4 and induced SMC proliferation, which relied on CD40-and P-selectin interactions. Flow-resistant monocyte adhesion to platelet EV-treated SMC was increased compared with resting SMC. Again, this adhesion depended on integrin a(11b)beta(3) and P-selectin, and to a lesser extent on CD40 and CX3CR1. Treatment of SMC with platelet EVs induced interleukin 6 secretion. Finally, platelet EVs induced a synthetic SMC morphology and decreased calponin expression. Collectively, these data indicate that platelet EVs exert a strong immunomodulatory activity on SMC. In particular, platelet EVs induce a switch towards a pro-inflammatory phenotype, stimulating vascular remodelling.

Original languageEnglish
Article number1322454
Number of pages14
JournalJournal of Extracellular Vesicles
Volume6
Issue number1
DOIs
Publication statusPublished - 16 May 2017

Keywords

  • Platelet factor 4
  • cytokine
  • synthetic phenotype
  • vascular remodeling
  • pathway analysis
  • proteomics
  • CX(3)CR1
  • NEOINTIMA FORMATION
  • ENDOTHELIAL-CELLS
  • CORONARY-ARTERY
  • ATHEROSCLEROTIC PLAQUES
  • MYOCARDIAL-INFARCTION
  • ACTIVATED PLATELETS
  • DEPENDENT MECHANISM
  • BETA(3) INTEGRIN
  • OUTGROWTH CELLS
  • VASCULAR INJURY

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