Renewal of mural thrombus releases plasma markers and is involved in aortic abdominal aneurysm evolution
Renewal of mural thrombus releases plasma markers and is involved in aortic abdominal aneurysm evolution
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DOI：
10.2353/ajpath.2006.050868
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发表时间：
2006-03-01
影响因子：
6
通讯作者：
Michel, JB
中科院分区：
文献类型：
--
作者：
Touat, Z;Ollivier, V;Michel, JB
人腹主动脉瘤（AAA）扩张与附壁血栓的存在有关。在这里，我们探讨了这种血栓的持续管腔更新的机制及其释放血浆中可能检测到的生物标记物的能力。我们还在实验模型中探索了血小板抑制剂安抚血栓和限制动脉瘤进展的能力。收集20例ANA患者的血液样本和附壁血栓。平行地，将十二烷基硫酸钠脱细胞化的豚鼠主动脉段异种移植到30只大鼠的腹主动脉上以诱导动脉瘤。15只大鼠接受阿昔单抗治疗，15只接受不相关的免疫球蛋白。与其他层相比，来自管腔血栓层的洗脱液中的促凝血活性和血小板活化标志物（微粒、sP-选择素、sGPV、sCD 40 L）增加了3倍至5倍。与对照组相比，患者血浆中所有这些标志物均增加2倍至5倍（P < 0.005）。在大鼠模型中，阿昔单抗可减少血栓面积和动脉瘤增大（P < 0.05）。血小板聚集可能是ANA血栓更新的原因。管腔血栓释放了血小板活化的标志物，这些标志物可以在血浆中容易地检测到。在大鼠模型中，血小板抑制限制了主动脉瘤扩张，为预防AAA扩大提供了新的治疗前景。
Human abdominal aortic aneurysm (AAA) expansion has been linked to the presence of a mural thrombus. Here we explored the mechanism of the continual luminal renewal of this thrombus and its ability to release biological markers potentially detectable in plasma. We also explored the ability of platelet inhibition to pacify the thrombus and to limit aneurysm progression in an experimental model. Blood samples and mural thrombi were collected in 20 ANA patients. in parallel, segments of sodium dodecyl sulfate-decellularized guinea pig aorta were xenografted onto the abdominal aorta of 30 rats to induce aneurysms. Fifteen rats received abciximab treatment and fifteen received irrelevant immunoglobulins. Procoagulant activity and platelet activation markers (microparticles, sP-selectin, sGPV, sCD40L) were increased threefold to fivefold in eluates from the luminal thrombus layer compared to other layers. All these markers were increased twofold to fivefold in patients' plasma compared to matched controls (P < 0.005). In the rat model, abciximab reduced both thrombus area and aneurysmal enlargement (P < 0.05). Platelet aggregation is probably responsible for the renewal of the thrombus in ANA. The luminal thrombus released markers of platelet activation that could easily be detected in plasma. Platelet inhibition limited aortic aneurysm expansion in a rat model, providing new therapeutic perspectives in the prevention of AAA enlargement.