Platelet extracellular vesicles induce a pro‐inflammatory smooth muscle cell phenotype. Issue 1 (1st December 2017)

• Record Type: Journal Article
• Authors: Vajen, Tanja; Benedikter, Birke J.; Heinzmann, Alexandra C. A.; Vasina, Elena M.; Henskens, Yvonne; Parsons, Martin; Maguire, Patricia B.; Stassen, Frank R.; Heemskerk, Johan W. M.; Schurgers, Leon J.; Koenen, Rory R.
• Is Part Of: Journal of extracellular vesicles. Volume 6:Issue 1(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-12-01
• Subjects: Platelet factor 4 -- cytokine -- synthetic phenotype -- vascular remodeling -- pathway analysis -- proteomics -- CX3CR1; Cells -- Mechanical properties -- Periodicals; Transport Vesicles; Cells -- Mechanical properties; Periodicals; Fulltext; Internet Resources; Periodicals; Electronic journals; Periodicals; 571.63
• DOI: 10.1080/20013078.2017.1322454
• Languages: English
• ISSNs: 2001-3078

Abstract

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 αIIb β3, 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 αIIb β3 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.