Jamaly S, Basavaraj M G, Starikova I, Olsen R, Braekkan S K, Hansen J-B
K.G. Jebsen Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway.
Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
J Thromb Haemost. 2018 May 31. doi: 10.1111/jth.14162.
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.
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.
重要的是，P选择素糖蛋白配体-1微泡（MVs）可能在静脉血栓栓塞症（VTE）中起重要作用。我们测量了不明原因VTE患者血浆中PSGL-1 MVs的水平及其亲本来源。VTE患者血浆中PSGL-1 MVs的水平高于健康对照。PSGL-1 MVs主要来源于单核细胞和内皮细胞。
背景 微泡（MVs）表达其亲本细胞的抗原，并且具有高度促凝的表面。动物研究表明，P选择素糖蛋白配体-1阳性（PSGL-1）MVs在静脉血栓栓塞症（VTE）的发病机制中起作用。目的 本研究的目的是确定不明原因VTE患者血浆中PSGL-1 MVs的水平、细胞来源和形态特征。方法 我们进行了一项基于人群的病例对照研究，纳入了20例有不明原因VTE病史的患者和20例从普通人群中招募的年龄和性别匹配的健康对照。使用流式细胞术、电子显微镜和共聚焦显微镜评估PSGL-1 MVs的血浆水平、细胞来源和形态特征。结果 PSGL-1 MVs的血浆水平与VTE风险增加相关。在调整年龄和性别后，PSGL-1 MVs每增加一个标准差，优势比为3.11（95%置信区间[CI]，1.41-6.88），在进一步调整体重指数后为2.88（95%CI，1.29-6.41）。通过使用流式细胞术和透射电子显微镜对亲本细胞标记物进行双重染色确定，PSGL-1 MVs主要来源于单核细胞和内皮细胞。对PSGL-1标记的血浆来源的MVs进行扫描电子显微镜检查，显示主要为直径在50至300 nm之间的球形囊泡。结论 PSGL-1 MVs血浆水平升高与不明原因VTE风险相关。需要进行大规模基于人群的前瞻性研究来验证我们的发现。
