The role of Endothelial microvesicles in thrombus formation

Abstract

Background: In the event of vascular injury, careful organisation of blood platelets and coagulation factor activation functions to stop blood loss. Endothelial-derived microvesicles (EMVs) are involved in coagulation, inflammation and endothelial dysfunction, all important processes in the development of cardiovascular disease (CVD). Contradicting reports suggest that EMVs have both a beneficial and a harmful role to play in these processes. Aim: Therefore the aim of this research is to understand the role of EMVs in coagulation by examining (I) the impact of EMVs on thrombus formation, (II) the lipid composition of EMVs and (III) the miRNA content of endothelial cells after EMV incubation. Methods: The effect of EMVs on thrombus formation and anticoagulant activity was determined using the Chandler Loop, immunohistochemistry, flow cytometry and an anticoagulant activated protein C activity assay. Lipidomic interrogated the behaviour of lipid headgroups and chain species, and miRNAs in EMVs were assessed using next generation sequencing in stimulated and unstimulated conditions. Results: Thrombi formed in the presence of exogenous EMVs were smaller and less solidified and possibly had enhanced anticoagulant activity. EMVs were incorporated into the thrombus. The phospholipid composition of EMVs was found to differ from the secreting cells with a possible enrichment of phosphorylated phosphatidyl inositol. miRNAs in EMVs appeared to target biological pathways involved in cell signalling and thrombus formation, and their content differed in EMVs from stimulated cells. Conclusion: EMVs are incorporated into the thrombi and may potentially reduce the extent of thrombus formation, protecting against thrombus formation. Some of the effects of EMVs may be mediated by phospholipids and miRNAs.

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Identifiers

ORCID for Giedo Elamin: orcid.org/0000-0002-9035-750X

ORCID for Nicola Englyst: orcid.org/0000-0003-0508-8323

ORCID for John Holloway: orcid.org/0000-0001-9998-0464

ORCID for Judith Holloway: orcid.org/0000-0002-2268-3071

ORCID for Philip Williamson: orcid.org/0000-0002-0231-8640

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