Circulating Microparticles from Patients with Septic Shock Exert Protective Role in Vascular Function
Circulating Microparticles from Patients with Septic Shock Exert Protective Role in Vascular Function
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DOI：
10.1164/rccm.200712-1835oc
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发表时间：
2008-12-01
影响因子：
24.7
通讯作者：
Andriantsitohaina, Ramaroson
中科院分区：
文献类型：
--
作者：
Mostefai, Hadj Ahmed;Meziani, Ferhat;Andriantsitohaina, Ramaroson
依据：脓毒症是一种典型疾病，炎症和凝血之间存在分子联系。这两个事件可以精心策划的循环和血管细胞之间的相互作用，激活下释放microbiots.Objectives：我们的特点是循环微粒从nonseptic科目和感染性休克患者，并评估其贡献vascular function.Methods：循环微粒和它们的细胞来源进行了测定，从36例感染性休克和18 nonseptic科目的血液中通过流式细胞术。然后将微粒静脉注射到小鼠体内，并在主动脉中评估血管反应性。参与一氧化氮（NO）和环氧合酶代谢产物的酶的表达和活性进行了analysed.Measurements和主要结果：循环水平的微粒和血小板和血小板衍生的微粒败血症患者增加。令人惊讶的是，脓毒性微粒增强了小鼠主动脉收缩对血清素的敏感性。有趣的是，脓毒性微粒增强了脂多糖处理小鼠的主动脉收缩。这种效应既不与钙离子进入增加有关，也不与Rho激酶敏感机制有关。此外，脓毒症微粒的作用不受NO合酶或环氧合酶-2抑制剂的影响，并且与NO或O（2）（-）过量产生无关。非选择性环氧合酶-2抑制剂吲哚美辛减少了用非脓毒症和脓毒症微粒处理的小鼠的主动脉收缩，而特异性血栓烷A2拮抗剂SQ-29548则消除了主动脉收缩。脓毒性微粒的作用与血栓素A（2）的产生增加有关，并且对选择性血栓素A（2）拮抗剂敏感。结论：我们提供的证据表明，增加循环微粒对脓毒性休克患者的血管低反应性具有保护作用。
Rationale: Sepsis is an archetypal condition with molecular links between inflammation and coagulation. Both events can be orchestrated by the interaction between circulating and vascular cells that under activation release microparticles.Objectives: We characterized circulating microparticles from both nonseptic subjects and patients with septic shock and evaluated their contribution to vascular function.Methods: Circulating microparticles and their cell origin were measured in blood from 36 patients with septic shock and 18 nonseptic subjects by flow cytometry. Microparticles were then injected intravenously into mice and vascular reactivity was assessed in aorta. Expression and activity of enzymes involved in nitric oxide (NO) and cyclooxygenase metabolite production were analyzed.Measurements and Main Results: Circulating levels of microparticles and platelet- and enclothelial-derived microparticles were increased in septic patients. Surprisingly, septic microparticles enhanced the sensitivity of contraction of mouse aorta in response to serotonin. Interestingly, septic microparticles enhanced the contraction of aorta from lipopolysaccharide-treated mice. This effect was linked neither to increased calcium entry nor to Rho kinase inhibitor-sensitive mechanisms. In addition, the effect of septic microparticles was not modified either by NO-synthase or cyclooxygenase-2 inhibitors, and was not associated with NO or O(2)(-) overproduction. The nonselective cyclooxygenase-2 inhibitor indomethacin reduced, and the specific thromboxane A(2) antagonist SQ-29548 abolished, aortic contraction in mice treated with nonseptic and septic microparticles. The effect of septic microparticles was associated with increased thromboxane A(2) production, and was sensitive to a selective thromboxane A(2) antagonist.Conclusions: We provide evidence that increased circulating microparticles are protective against vascular hyporeactivity accounting for hypotension in patients with septic shock.