Morel Olivier, Hugel Bénédicte, Jesel Laurence, Lanza François, Douchet Marie-Pierre, Zupan Michel, Chauvin Michel, Cazenave Jean-Pierre, Freyssinet Jean-Marie, Toti Florence
Féderation de Cardiologie des Hôspitaux Universitaires de Strasbourg, Strasbourg, France.
Thromb Haemost. 2004 Feb;91(2):345-53. doi: 10.1160/TH03-05-0294.
During myocardial infarction (MI), platelet activation and endothelial apoptosis are responsible for the release of procoagulant membrane-derived microparticles (MP) in the blood flow. MP prothrombotic and proinflammatory properties may be crucial for coronary prognosis. Elevated amounts of circulating procoagulant MP were described in diabetes mellitus (DM), and could be of particular significance in a MI context. We evaluated the prothrombotic status of DM and non-DM (NDM) patients at days 1 and 6 after MI, by measurement of circulating procoagulant MP and soluble GPV (sGPV), the platelet glycoprotein V major fragment released upon thrombin cleavage. Variations were compared to values measured in healthy volunteers (HV). Procoagulant MP were captured onto insolubilized annexin V and quantified by prothrombinase assay. Their cellular origin was assessed. With respect to HV, the levels of procoagulant MP detected at D1 and D6 were elevated in DM and NDM, MP being significantly higher in DM vs. NDM. The high amounts of platelet-derived MP and the correlation between procoagulant MP and sGPV, testify to the central role of thrombin-activated platelets during MI in both DM and NDM subsets. The release of platelet and endothelial cell-derived MP persisted at D6 and was more important in DM, the associated prothrombotic risk being also reflected by higher levels of sGPV. The endothelial damage revealed by endothelial-derived MP was twice that observed in NDM patients. In DM patients presenting cardio-vascular events at 6 month follow-up, MP levels were significantly higher at D1 after MI than in those without complication (24.9 +/- 4.8 vs. 12.3 +/- 2.7 nM PhtdSer, p = 0.02), suggesting a prognostic potential for MP.
在心肌梗死(MI)期间,血小板活化和内皮细胞凋亡导致血流中促凝血性膜衍生微粒(MP)的释放。MP的促血栓形成和促炎特性可能对冠状动脉预后至关重要。糖尿病(DM)患者循环促凝血性MP水平升高,在MI背景下可能具有特殊意义。我们通过测量循环促凝血性MP和可溶性糖蛋白V(sGPV,凝血酶裂解后释放的血小板糖蛋白V主要片段),评估了MI后第1天和第6天DM和非DM(NDM)患者的促血栓形成状态。将这些变化与健康志愿者(HV)测量的值进行比较。促凝血性MP被捕获到固定化的膜联蛋白V上,并通过凝血酶原酶测定进行定量。评估了它们的细胞来源。与HV相比,DM和NDM患者在第1天和第6天检测到的促凝血性MP水平升高,DM患者的MP明显高于NDM患者。大量血小板衍生的MP以及促凝血性MP与sGPV之间的相关性,证明了凝血酶激活的血小板在DM和NDM亚组的MI过程中起核心作用。血小板和内皮细胞衍生的MP在第6天仍持续释放,且在DM中更明显,sGPV水平升高也反映了相关的促血栓形成风险。内皮细胞衍生的MP所揭示的内皮损伤是NDM患者的两倍。在6个月随访中出现心血管事件的DM患者中,MI后第1天的MP水平显著高于无并发症患者(24.9±4.8对12.3±2.7 nM磷脂酰丝氨酸,p = 0.02),提示MP具有预后潜力。