Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction
Circulating microparticles from patients with myocardial infarction cause endothelial dysfunction
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DOI：
10.1161/hc4701.100516
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发表时间：
2001-11-27
期刊：
影响因子：
37.8
通讯作者：
Mallat, Z
中科院分区：
文献类型：
--
作者：
Boulanger, CM;Scoazec, A;Mallat, Z
背景-脱落膜微粒在非缺血性（NI）患者和心肌梗死（MI）患者的外周血中循环。我们调查这些微粒是否会影响内皮依赖性responses.Methods和Results-Rat主动脉环内皮细胞暴露24小时循环微粒分离出7例NI综合征和19例急性心肌梗死。内皮依赖性舒张乙酰胆碱不受高浓度的微粒NI患者（P=0.80）。然而，在暴露于低浓度和高浓度MI患者微粒的制剂中观察到显著损害，对应于0.7倍和2倍循环血浆水平（分别为P=0.05和0.001）。损伤不受双氯芬酸（P=0.47），也不受细胞渗透性超氧化物歧化酶模拟物Mn（III）四（4-苯甲酸）卟啉氯化物（P=0.33），但它被废除内皮细胞去除或N（ω）单甲基-L-精氨酸。在暴露于MI患者微粒的环中，对钙离子载体离子霉素的舒张作用降低（低浓度和高浓度分别为P=0.05和0.009），但NI患者的微粒没有影响（P=0.81）。最后，来自MI患者的高浓度微粒既不影响对硝普钠的内皮非依赖性舒张，（P=0.59）内皮型一氧化氮合酶的表达（P=0.43）.结论-来自MI患者的循环微粒选择性地损害内皮一氧化氮转导途径，因此，可能导致MI后观察到的一般血管功能障碍，即使在血管造影正常的动脉中。
Background-Shed membrane microparticles circulate in the peripheral blood of nonischemic (NI) patients and patients with myocardial infarction (MI). We investigated whether or not these microparticles would affect endothelium-dependent responses.Methods and Results-Rat aortic rings with endothelium were exposed for 24 hours to circulating microparticles isolated from 7 patients with NI syndromes and 19 patients with acute MI. Endothelium-dependent relaxations to acetylcholine were not affected by high concentrations of microparticles from NI patients (P=0.80). However, significant impairment was observed in preparations exposed to microparticles from patients with MI at low and high concentrations, corresponding to 0.7-fold and 2-fold circulating plasma levels (P=0.05 and 0.001, respectively). Impairment was not affected by diclofenac (P=0.47), nor by the cell-permeable superoxide dismutase mimetic Mn(III)tetra(4-benzoic acid) porphyrin chloride (P=0.33), but it was abolished by endothelium removal or by N(omega)monomethyl-L-arginine. Relaxations to the calcium ionophore ionomycin were decreased in rings exposed to microparticles from MI patients (P=0.05 and 0.009 for low and high concentrations, respectively), but microparticles from NI patients had no effect (P=0.81). Finally, high concentrations of microparticles from MI patients affected neither endothelium-independent relaxation to sodium nitroprusside (P=0.59) nor expression of the endothelial nitric oxide synthase (P=0.43).Conclusions-Circulating microparticles from patients with MI selectively impair the endothelial nitric oxide transduction pathway and, therefore, could contribute to the general vasomotor dysfunction observed after MI, even in angiographically normal arteries.