التفاصيل البيبلوغرافية
| العنوان: |
A new assay to evaluate microvesicle plasmin generation capacity: validation in disease with fibrinolysis imbalance. |
| المؤلفون: |
Cointe, Sylvie, Harti Souab, Karim, Bouriche, Tarik, Vallier, Loris, Bonifay, Amandine, Judicone, Coralie, Robert, Stéphane, Armand, Romain, Poncelet, Philippe, Albanese, Jacques, Dignat-George, Françoise, Lacroix, Romaric |
| المصدر: |
Journal of Extracellular Vesicles; Dec2018, Vol. 7 Issue 1, p1-1, 1p |
| مصطلحات موضوعية: |
FIBRINOLYSIS, SEPTIC shock, VESICLES (Cytology) |
| مستخلص: |
Among extracellular vesicles, leukocyte-derived microvesicles (LMVs) have emerged as complex vesicular structures. Primarily identified as procoagulant entities, they were more recently ascribed to plasmin generation capacity (MV-PGC). The objectives of this work were (1) to develop a new hybrid bio-assay combining the specific isolation of LMVs and measurement of their PGC, and compare its performance to the original method based on centrifugation, (2) to validate MV-PGC in septic shock, combining increased levels of LMVs and fibrinolytic imbalance. Using plasma sample spiked with LMVs featuring different levels of PGC, we demonstrated that CD15-beads specifically extracted LMVs. The MV dependency of the test was demonstrated using electron microscopy, high speed centrifugation, nanofiltration and detergent-mediated solubilization and the MV-PGC specificity using plasmin-specific inhibitors, or antibodies blocking elastase or uPA. Thanks to a reaction booster (ε-ACA), we showed that the assay was more sensitive and reproducible than the original method. Moreover, it exhibited a good repeatability, inter-operator and inter-experiment reproducibility. The new immunomagnetic bio-assay was further validated in patients with septic shock. As a result, we showed that MV-PGC values were significantly lower in septic shock patients who died compared to patients who survived, both at inclusion and 24 h later (1.4 [0.8-3.0] vs 3.1 [1.7-18] A405 × 10−3/min, p = 0.02; 1.4 [1-1.6] vs 5.2 [2.2-16] A405 × 10−3/min, p = 0.004). Interestingly, combining both MV-PGC and PAI-1 in a ratio significantly improved the predictive value of PAI-1. This strategy, a hybrid capture bioassay to specifically measure LMV-PGC using for the first time, opens new perspectives for measuring subcellular fibrinolytic potential in clinical settings with fibrinolytic imbalance. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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