Factor VIIa releases phosphatidylserine-enriched extracellular vesicles from endothelial cells by activating acid sphingomyelinase.

ABSTRACT:

Background

Our recent studies showed that activated factor (F) VII (FVIIa) releases extracellular vesicles (EVs) from the endothelium. FVIIa-released EVs were found to be enriched with phosphatidylserine (PS) and contribute to the hemostatic effect of FVIIa in thrombocytopenia and hemophilia.

Objective

To investigate mechanisms by which FVIIa induces EV biogenesis and enriches EVs with PS.

Methods

FVIIa activation of acid sphingomyelinase (aSMase) was evaluated by its translocation to the cell surface. The role of aSMase in the biogenesis of FVIIa-induced EVs and their enrichment with PS was investigated using specific siRNAs and inhibitors of aSMase and its downstream metabolites. Wild-type and aSMase^-/- mice were injected with a control vehicle or FVIIa.

SUBMITTER: Das K 

PROVIDER: S-EPMC11770839 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature