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.

Thrombin Binding Predicts the Effects of Sequence Changes in a Human Monoclonal Antiphospholipid Antibody on Its In Vivo Biologic Actions

“…Dignat-George et al (22) found circulating EMP to be elevated in patients with APS (with vascular thromboses but no pregnancy morbidity) and systemic lupus erythematosus patients with aPL but not in systemic lupus erythematosus patients without aPL or in non-aPL-related venous thrombosis (22). Although Jy et al (40) found EMP to be elevated in all patients with (thrombotic and nonthrombotic) APS.…”

“…Recently, VCAM-1 has been shown to be expressed en face in ex vivo arterial endothelium from mice pretreated with human aPL (20,21). Furthermore, aPL have been shown to promote endothelial microparticle (EMP) production (22,23). EMPs are released from EC during activation or apoptosis and are known to be procoagulant in vitro, via a tissue factor-dependent pathway (23).…”

Leukocyte- and endothelial-derived microparticles: a circulating source for fibrinolysis

“…Nevertheless, we have revealed the existence of a microparticle-dependent profibrinolytic compensatory mechanism that may counterbalance the procoagulant phenotype and reduce the thrombotic risk in these patients. 24,[27][28][29] These interesting features lay the basis for a potential new biomarker.…”

“…30 Interestingly, we found various levels of fibrinolytic microparticles in differents pathological situations (atherosclerosis, systemic lupus erythematosus, TTP) that have been reported to be associated with increased levels of leukocyte and endothelial microparticles. 13,19,27,28,[31][32][33][34] This fibrinolytic activity may reflect pathophysiological leuko-endothelial activation associated with inflammation, which could help to identify patients with a higher individual vascular risk in these clinical situations. Of note, leukocyte and endothelial Differential fibrinolytic effects of microparticles haematologica | 2012; 97 (12) 1869 Non-activated platelets microparticles are among the circulating subsets least accessible by current methodologies, such as flow cytometry, because of their low proportion, size distribution and limited specific markers.…”

Comparative proteomic analysis of PAI‐1 and TNF‐alpha‐derived endothelial microparticles

“…Elevated concentrations of EMPs have been linked to many inflammatory and vascular diseases including diabetes [22], renal failure [23], acute myocardial infarction [24], cancer [25], vasculitis [26], and sickle cell disease [27]. In addition, the EMPs of patients with systemic lupus erythematosus and antiphospholipid syndrome have a significant increase in quantity as well as procoagulant activity as compared to the EMPs of healthy individuals [28]. This suggests that EMP function may be different in diseased patients as compared to healthy controls.…”