| Title: |
Platelets: Old Players Revisited |
| Authors: |
Vajen, T; Vasina, EM; Heemskerk, JWM; Schurgers, LJ; Weber, C; Hackeng, TM; Koenen, RR; Rami, M; Ring, L; Horckmans, M; Duchene, J; Megens, R; Soehnlein, O; Steffens, S; Zhao, Z; Karshovska, E; Schmitt, M; Von Hundelshausen, P; Koeppel, TA; Koenen, R |
| Publisher Information: |
Oxford University Press |
| Publication Year: |
2016 |
| Collection: |
HighWire Press (Stanford University) |
| Subject Terms: |
Saturday 9 July 2016 |
| Description: |
Background: Microvesicles are gathering increasing attention as mediators of cell communication and as integral effectors of disease. Platelets present a major source of microvesicles and release these microvesicles either spontaneously or upon activation. Platelet microvesicles (PMVs) retain many features of their parent cells and have been shown to exert modulatory effects on vascular and immune cells. Purpose: We hypothesize that PMVs interact with vascular smooth muscle cells (SMCs) and modulate their function in the context of vascular remodeling. Methods: PMVs were isolated from aging human platelet concentrates by serial centrifugation steps. PMVs were quantified and characterized by flow cytometry using annexin A5/phosphatidylserine and antibodies against CD41a/GPIIb. Size calibrated micro beads were used to quantify the absolute amount of PMVs/mL. Cell migration experiments were performed using a boyden chemotaxis chamber. Platelet receptors implicated in PMV-SMC interaction were identified by blocking antibodies. Proliferation of SMCs was measured by the BrdU-cell proliferation kit. Adhesion of monocytic cells to SMCs was determined by a flow adhesion assay. Relative quantification of gene expression was determined by real time and quantitative PCR. Results: In the presence of PMVs, SMCs show increased migration. Under resting conditions, the PMV binding to SMCs was specifically abrogated by the integrin αIIbβ3 inhibitor (integrilin) indicating an integrin-dependent mechanism of interaction. A proliferative effect on SMCs was measured after 48 hours after incubation with PMVs and this proliferation relied on interactions via integrin αMβ2, CD40 and P-selectin. The firm adhesion of monocytic cells to PMVs stimulated SMCs under flow conditions was significantly increased compared to untreated, resting SMCs. The adhesion mainly depended on the integrin αIIbβ3 and P-selectin but also CD40 and fractalkine. PMVs decreased gene expression of contractile proteins, i.e. αSMA and calponin. Conclusion: Isolated ... |
| Document Type: |
text |
| File Description: |
text/html |
| Language: |
English |
| Relation: |
http://cardiovascres.oxfordjournals.org/cgi/content/short/111/suppl_1/S55; http://dx.doi.org/10.1093/cvr/cvw148 |
| DOI: |
10.1093/cvr/cvw148 |
| Availability: |
http://cardiovascres.oxfordjournals.org/cgi/content/short/111/suppl_1/S55; https://doi.org/10.1093/cvr/cvw148 |
| Rights: |
Copyright (C) 2016, European Society of Cardiology |
| Accession Number: |
edsbas.140964E6 |
| Database: |
BASE |