Blocking endothelial protein C receptor (EPCR) accelerates thrombus development in vivo
Blocking endothelial protein C receptor (EPCR) accelerates thrombus development in vivo
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DOI：
10.1160/th09-11-0750
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发表时间：
2010-06-01
影响因子：
6.7
通讯作者：
Hermida, Jose
中科院分区：
文献类型：
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作者：
Centelles, Miguel N.;Puy, Cristina;Hermida, Jose
内皮蛋白C受体（EPCR）通过提高蛋白C的活化而发挥抗凝作用。虽然低水平的活化蛋白C（APC）构成血栓形成的危险因素，调节EPCR功能和血栓形成之间的关系尚未得到解决。制备了抗鼠EPCR的单克隆抗体（mAb），并测试了其阻断蛋白C/APC结合的能力。采用小鼠颈动脉氯化铁损伤模型，观察抗EPCR单克隆抗体对血栓形成的影响。在三组中分析了至血管完全闭塞的时间，给予同种型对照mAb（IC）、阻断（RCR-16）或非阻断（RCR-20）抗EPCR mAb。表面等离子体共振和流式细胞仪检测显示，RCR-16可阻断Protein C/APC与EPCR的相互作用，抑制内皮细胞上Protein C的活化。IC和RCR-20不能诱导这种作用。在体内，相对于IC，RCR-16缩短了血管完全闭塞的时间[分别为13.4 +/- 1.0（平均值+/- SD）和17.8 +/- 3.2分钟，p
The endothelial protein C receptor (EPCR) plays an anticoagulant role by improving protein C activation. Although low levels of activated protein C (APC) constitute a thrombosis risk factor, the relationship between modulating EPCR function and thrombosis has not been addressed so far. Monoclonal antibodies (mAb) against murine EPCR were raised, and their ability to block protein C/APC binding was tested. The ferric chloride carotid artery injury model in mice was chosen to test the effect of anti-EPCR mAb on thrombus formation. The time to total occlusion of the vessel was analysed in three groups, given an isotype control mAb (IC), a blocking (RCR-16) or a non-blocking (RCR-20) anti-EPCR mAb. RCR-16 prevented the interaction between protein C/APC and EPCR as demonstrated by surface plasmon resonance and flow cytometry, and inhibited the activation of protein C on the endothelium. IC and RCR-20 were unable to induce such effects. In vivo, RCR-16 shortened the time to total vessel occlusion with respect to IC [13.4 +/- 1.0 (mean +/- SD) and 17.8 +/- 3.2 minutes, respectively, p