S Jamaly1, M G Basavaraj1, I Starikova1,2, R Olsen3, S K Braekkan1,2, J-B Hansen1,2. 1. K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway. 2. Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway. 3. Advanced Microscopy Core Facility, Institute of Medical Biology, Faculty of Health Sciences, UiT - The Arctic University of Norway, Tromsø, Norway.
Abstract
Essentials PSGL-1+ microvesicles (MVs) may be important in venous thromboembolism (VTE). We measured plasma levels and parental origin of PSGL-1+ MVs in patients with unprovoked VTE. VTE patients had higher plasma levels of PSGL-1+ MVs than healthy controls. The PSGL-1+ MVs originated mainly from monocytes and endothelial cells. SUMMARY: Background Microvesicles (MVs) express antigens from their parental cells and have a highly procoagulant surface. Animal studies suggest that P-selectin glycoprotein ligand-1-positive (PSGL-1+ ) MVs play a role in the pathogenesis of venous thromboembolism (VTE). Objective The aim of this study was to determine plasma levels, the cellular origin and the morphological characteristics of PSGL-1+ MVs in patients with unprovoked VTE. Methods We conducted a population-based case-control study in 20 patients with a history of unprovoked VTE and 20 age- and sex-matched healthy controls recruited from the general population. Plasma levels, the cellular origin and the morphological characteristics of PSGL-1+ MVs were evaluated using flow cytometry, electron microscopy and confocal microscopy. Results Plasma levels of PSGL-1+ MVs were associated with increased risk of VTE. The odds ratio per one standard deviation increase in PSGL-1+ MVs was 3.11 (95% confidence interval [CI], 1.41-6.88) after adjustment for age and sex, and 2.88 (95% CI, 1.29-6.41) after further adjustment for body mass index. The PSGL-1+ MVs originated mainly from monocytes and endothelial cells determined by double staining with markers of parental cells using flow cytometry and transmission electron microscopy. Scanning electron microscopy of PSGL-1-labeled plasma-derived MVs displayed dominantly spherical vesicles that varied between 50 and 300 nm in diameter. Conclusions Increased plasma levels of PSGL-1+ MVs are associated with the risk of unprovoked VTE. Large population-based prospective studies are required to validate our findings.
Essentials PSGL-1+ microvesicles (MVs) may be important in venous thromboembolism (VTE). We measured plasma levels and parental origin of PSGL-1+ MVs in patients with unprovoked VTE. VTEpatients had higher plasma levels of PSGL-1+ MVs than healthy controls. The PSGL-1+ MVs originated mainly from monocytes and endothelial cells. SUMMARY: Background Microvesicles (MVs) express antigens from their parental cells and have a highly procoagulant surface. Animal studies suggest that P-selectin glycoprotein ligand-1-positive (PSGL-1+ ) MVs play a role in the pathogenesis of venous thromboembolism (VTE). Objective The aim of this study was to determine plasma levels, the cellular origin and the morphological characteristics of PSGL-1+ MVs in patients with unprovoked VTE. Methods We conducted a population-based case-control study in 20 patients with a history of unprovoked VTE and 20 age- and sex-matched healthy controls recruited from the general population. Plasma levels, the cellular origin and the morphological characteristics of PSGL-1+ MVs were evaluated using flow cytometry, electron microscopy and confocal microscopy. Results Plasma levels of PSGL-1+ MVs were associated with increased risk of VTE. The odds ratio per one standard deviation increase in PSGL-1+ MVs was 3.11 (95% confidence interval [CI], 1.41-6.88) after adjustment for age and sex, and 2.88 (95% CI, 1.29-6.41) after further adjustment for body mass index. The PSGL-1+ MVs originated mainly from monocytes and endothelial cells determined by double staining with markers of parental cells using flow cytometry and transmission electron microscopy. Scanning electron microscopy of PSGL-1-labeled plasma-derived MVs displayed dominantly spherical vesicles that varied between 50 and 300 nm in diameter. Conclusions Increased plasma levels of PSGL-1+ MVs are associated with the risk of unprovoked VTE. Large population-based prospective studies are required to validate our findings.