The ICAM-1 expression level determines the susceptibility of human endothelial cells to simulated microgravity
The ICAM-1 expression level determines the susceptibility of human endothelial cells to simulated microgravity
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DOI：
10.1002/jcb.26465
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发表时间：
2018-03-01
影响因子：
4
通讯作者：
Grigoriev, Anatoly I.
中科院分区：
文献类型：
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作者：
Buravkova, Ludmila B.;Rudimov, Eugene G.;Grigoriev, Anatoly I.
在太空飞行中，微重力是阻碍人类心血管调节的主要危险因素。内皮功能障碍与单层完整性和均匀性受损相关，是血管损伤的潜在触发因素。我们对暴露于模拟微重力（SMG）环境24小时后脐带内皮细胞（ECs）中粘附分子（ICAM-1、VCAM-1、e -选择素、VE-cadherin）、促炎细胞因子tnf - α以及两者结合的多步级联表达谱进行了表征。随机定位机（RPM）介导的SMG模拟微重力效应。SMG刺激e -选择素的表达，已知e -选择素参与减缓白细胞滚动。原代上皮细胞在icam -1阳性细胞比例方面表现出异质性。将ECs分为两组：预激活ECs， ICAM-1(+)-细胞比例高（大于50%）和未激活ECs， ICAM-1(+)-细胞比例低（小于25%）。只有未激活的ECs-2通过提高基因转录和增加ICAM-1和VE-cadherin表达来响应SMG。这种效应在累积的smg - tnf - α暴露后增强。炎症激活后，ECs-1显示出e -选择素和icam -1阳性ECs数量的意外减少，VCAM1明显上调，而SMG部分消除了这一作用。因此，未激活的ec -2对微重力的影响具有很强的抵抗力，甚至表现出VE-cadherin基因和蛋白表达的升高，从而提高了内皮单层的完整性。用炎症刺激预激活EC可能会扰乱EC的粘附谱，减弱其屏障功能。这些改变可能是真实微重力条件下心血管失调的机制之一。
Microgravity is a principal risk factor hampering human cardiovascular regulation during space flights. Endothelial dysfunction associated with the impaired integrity and uniformity of the monolayer represents a potential trigger for vascular damage. We characterized the expression profile of the multi-step cascade of adhesion molecules (ICAM-1, VCAM-1, E-selectin, VE-cadherin) in umbilical cord endothelial cells (ECs) after 24h of exposure to simulated microgravity (SMG), pro-inflammatory cytokine TNF-alpha, and the combination of the two. Random Positioning Machine (RPM)-mediated SMG was used to mimic microgravity effects. SMG stimulated the expression of E-selectin, which is known to be involved in slowing leukocyte rolling. Primary ECs displayed heterogeneity with respect to the proportion of ICAM-1-positive cells. ECs were divided into two groups: pre-activated ECs displaying high proportion of ICAM-1(+)-cells (ECs-1) (greater than 50%) and non-activated ECs with low proportion of ICAM-1(+)-cells (ECs-2) (less than 25%). Only non-activated ECs-2 responded to SMG by elevating gene transcription and increasing ICAM-1 and VE-cadherin expression. This effect was enhanced after cumulative SMG-TNF-alpha exposure. ECs-1 displayed an unexpected decrease in number of E-selectin- and ICAM-1-positive ECs and pronounced up-regulation of VCAM1 upon activation of inflammation, which was partially abolished by SMG. Thus, non-activated ECs-2 are quite resistant to the impacts of microgravity and even exhibited an elevation of the VE-cadherin gene and protein expression, thus improving the integrity of the endothelial monolayer. Pre-activation of ECs with inflammatory stimuli may disturb the EC adhesion profile, attenuating its barrier function. These alterations may be among the mechanisms underlying cardiovascular dysregulation in real microgravity conditions.