Disturbed blood flow acutely induces activation and apoptosis of the human vascular endothelium.
Disturbed blood flow acutely induces activation and apoptosis of the human vascular endothelium.
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DOI：
10.1161/hypertensionaha.111.00561
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发表时间：
2013-03
期刊：
影响因子：
--
通讯作者：
Fadel PJ
中科院分区：
文献类型：
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作者：
Jenkins NT;Padilla J;Boyle LJ;Credeur DP;Laughlin MH;Fadel PJ
有来自体外研究的强有力和一致的证据表明，血流紊乱会产生促动脉粥样硬化血管内皮表型。然而，缺乏人体研究的数据。为了解决这个问题，在10名年轻健康男性的前臂远端放置一个220毫米汞柱的闭塞袖带，以诱导近端脉管系统局部血流紊乱20分钟。我们假设血流紊乱会诱导内皮细胞活化和凋亡，这可以通过局部CD62E+和CD31+/CD42b−内皮微粒浓度的增加来证明。远端袖带闭塞导致平均血流量、平均剪切和顺行剪切减少，以及逆行血流、逆行剪切和振荡剪切应力增加，证实我们的方案在实验臂中产生了紊乱的血流刺激。与基线（0 min）相比，实验组CD62E+内皮微粒在10 min和20 min分别增加了~3倍和~4倍（P < 0.05）。CD31+/CD42b−内皮微粒在20 min时升高约9倍（P < 0.05）。在整个实验过程中，暴露于正常静息血流（无袖带）的对侧手臂中内皮微粒群的浓度均未发生变化。这些发现表明，受干扰的血流急性诱导内皮细胞活化和凋亡，这反映在活化的（CD62E+）和凋亡的（CD31+/CD42b−）内皮细胞释放的微粒上。这些数据为血流紊乱引起的人类内皮损伤提供了第一个体内实验证据。
There is strong and consistent evidence from in vitro studies that disturbed blood flow produces a pro-atherogenic vascular endothelial phenotype. However, data from human studies are lacking. To address this, a 220 mmHg occlusion cuff was placed on the distal forearm of 10 young, healthy men to induce a localized region of disturbed blood flow in the proximal vasculature for 20 min. We hypothesized that disturbed blood flow would induce endothelial activation and apoptosis as indicated by increases in local concentrations of CD62E+ and CD31+/CD42b− endothelial microparticles, respectively. Distal cuff occlusion induced reductions in mean blood flow, mean shear and antegrade shear, and increases in retrograde flow, retrograde shear and oscillatory shear stress, confirming that our protocol produced a disturbed blood flow stimulus in the experimental arm. Relative to baseline (0 min), CD62E+ endothelial microparticles increased by ~3 fold at 10 min and ~4 fold at 20 min in the experimental arm (P < 0.05). CD31+/CD42b− endothelial microparticles were elevated by ~9 fold at the 20 min time point (P < 0.05). There were no changes in the concentrations of either endothelial microparticle population throughout the experiment in the contralateral arm, exposed to normal resting blood flow (no cuffs). These findings indicate that disturbed blood flow acutely induces endothelial activation and apoptosis in humans, as reflected by release of microparticles from activated (CD62E+) and apoptotic (CD31+/CD42b−) endothelial cells. These data provide the first in vivo experimental evidence of disturbed blood flow-induced endothelial injury in humans.