title: Endothelial microparticles: a potential contribution to the thrombotic complications of the antiphospholipid syndrome.
abstract: The antiphospholipid syndrome (APS) refers to persistent anti-phospholipid antibodies (aPL) associated with thrombotic and/or obstetrical complications. The endothelial cell is a target of aPL which can induce a procoagulant and proinflammatory endothelial phenotype, as reported both in vivo and in vitro. Microparticle production is a hallmark of cell activation. In the present study, the presence of endothelial microparticles (EMP) in the plasma of APS patients was investigated. To determine if there is a correlation with certain biological and clinical features, EMP levels were measured in thrombosis-free patients with systemic lupus erythematosus (SLE) patients, with and without aPL, in patients with non aPL-related thrombosis, as well as in healthy controls. Compared to healthy subjects, elevated plasma levels of EMP were found in patients with APS and in SLE patients with aPL, but not in SLE patients without aPL or in non aPL-related thrombosis. EMP levels were also associated with Lupus Anticoagulant (LA) detected by a positive Dilute Russell's Viper Venom time (DRVVT). In parallel, we analyzed the capacity of these plasma to induce vesiculation of cultured endothelial cells. We demonstrated an increase of EMP generated in response to plasma from patients with auto-immune diseases. Interestingly, only APS plasma induced the release of EMP with procoagulant activity. These ex vivo and in vitro observations indicate that generation of EMP in APS and SLE patients results from an autoimmune process involving aPL. Production of procoagulant microparticles in APS patients may represent a new pathogenic mechanism for the thrombotic complications of this disease.
authors.affiliation: INSERM EMI 0019: Physiopathology of the endothelium, UFR de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France. dignat@pharmacie.univ-mrs.fr
authors.forename: Françoise
authors.initials: F
authors.lastname: Dignat-George
authors.forename: Laurence
authors.initials: L
authors.lastname: Camoin-Jau
authors.forename: Florence
authors.initials: F
authors.lastname: Sabatier
authors.forename: Dominique
authors.initials: D
authors.lastname: Arnoux
authors.forename: Francine
authors.initials: F
authors.lastname: Anfosso
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bardin
authors.forename: Véronique
authors.initials: V
authors.lastname: Veit
authors.forename: Valéry
authors.initials: V
authors.lastname: Combes
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Gentile
authors.forename: Valérie
authors.initials: V
authors.lastname: Moal
authors.forename: Marielle
authors.initials: M
authors.lastname: Sanmarco
authors.forename: José
authors.initials: J
authors.lastname: Sampol
mesh_terms: D000328:Adult; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000473:pathology*; D001780:Blood Coagulation Tests; D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000473:pathology / Q000648:ultrastructure*; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D013927:Thrombosis / Q000209:etiology* / Q000473:pathology