Platelet-derived exosomes from septic shock patients induce myocardial dysfunction.
Platelet-derived exosomes from septic shock patients induce myocardial dysfunction.
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DOI：
10.1186/cc6176
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Laurindo FR
中科院分区：
文献类型：
--
作者：
Azevedo LC;Janiszewski M;Pontieri V;Pedro Mde A;Bassi E;Tucci PJ;Laurindo FR
败血性休克中肌力衰竭的机制尚不完全清楚。我们之前在感染性休克患者的血浆中发现了外泌体的存在。这些外泌体主要通过血小板释放，产生超氧化物，并通过氧化还原依赖途径诱导血管细胞凋亡。我们假设循环血小板来源的外泌体可能导致败血症的肌力功能障碍。我们采集了55例感染性休克患者和12名健康志愿者的血液样本进行外泌体分离。研究了化脓症患者和健康人的外泌体在离体心脏和乳头肌制剂中的心肌抑制作用。脓毒症患者血浆中的外泌体显著降低离体兔心脏左心室压力的正、负衍生物或在乳头肌中产生张力及其第一个正衍生物。来自健康个体的外泌体没有显著降低这些变量。在先前暴露于内毒素的家兔心脏中，败血性外泌体降低了心室压的正、负衍生物。这种负性肌力作用在退出外泌体后是完全可逆的。用荧光法证实感染性休克患者外泌体产生一氧化氮（NO）。此外，暴露于败血性外泌体后心肌硝酸盐含量增加。来自脓毒症患者的循环血小板衍生外泌体在分离的心脏和乳头肌制剂中诱导心肌功能障碍，这一现象因先前体内暴露于脂多糖而增强。脓毒症患者的外泌体产生一氧化氮以及与脓毒症患者的外泌体孵育后心肌硝酸盐含量增加，提示一氧化氮依赖机制可能导致脓毒症的心肌功能障碍。
Mechanisms underlying inotropic failure in septic shock are incompletely understood. We previously identified the presence of exosomes in the plasma of septic shock patients. These exosomes are released mainly by platelets, produce superoxide, and induce apoptosis in vascular cells by a redox-dependent pathway. We hypothesized that circulating platelet-derived exosomes could contribute to inotropic dysfunction of sepsis. We collected blood samples from 55 patients with septic shock and 12 healthy volunteers for exosome separation. Exosomes from septic patients and healthy individuals were investigated concerning their myocardial depressant effect in isolated heart and papillary muscle preparations. Exosomes from the plasma of septic patients significantly decreased positive and negative derivatives of left ventricular pressure in isolated rabbit hearts or developed tension and its first positive derivative in papillary muscles. Exosomes from healthy individuals decreased these variables non-significantly. In hearts from rabbits previously exposed to endotoxin, septic exosomes decreased positive and negative derivatives of ventricular pressure. This negative inotropic effect was fully reversible upon withdrawal of exosomes. Nitric oxide (NO) production from exosomes derived from septic shock patients was demonstrated by fluorescence. Also, there was an increase in myocardial nitrate content after exposure to septic exosomes. Circulating platelet-derived exosomes from septic patients induced myocardial dysfunction in isolated heart and papillary muscle preparations, a phenomenon enhanced by previous in vivo exposure to lipopolysaccharide. The generation of NO by septic exosomes and the increased myocardial nitrate content after incubation with exosomes from septic patients suggest an NO-dependent mechanism that may contribute to myocardial dysfunction of sepsis.
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影响因子：
20.3
作者：
Nieuwland, R;Berckmans, RJ;Sturk, A
通讯作者：
Sturk, A
影响因子：
4.6
作者：
Paulus, Walter J;Bronzwaer, Jean G F
通讯作者：
Bronzwaer, Jean G F
DOI：
10.1152/ajpheart.1999.276.6.h1861
发表时间：
1999-06-01
影响因子：
4.8
作者：
Ferdinandy, P;Panas, D;Schulz, R
通讯作者：
Schulz, R
影响因子：
4.8
作者：
Clayton, A;Turkes, A;Hallett, MB
通讯作者：
Hallett, MB
影响因子：
8.8
作者：
Janiszewski, M;do Carmo, AO;Laurindo, FRM
通讯作者：
Laurindo, FRM