Fluid flow inhibits endothelial adhesiveness - Nitric oxide and transcriptional regulation of VCAM-1
Fluid flow inhibits endothelial adhesiveness - Nitric oxide and transcriptional regulation of VCAM-1
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DOI：
10.1161/01.cir.94.7.1682
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发表时间：
1996-10-01
期刊：
影响因子：
37.8
通讯作者：
Cooke, JP
中科院分区：
文献类型：
--
作者：
Tsao, PS;Buitrago, R;Cooke, JP
背景在动脉树中，暴露于降低的剪切应力（低和/或扰动的流动）的区域易发生动脉粥样硬化。流体流动是内皮源性一氧化氮（NO）释放的有力刺激。由于NO抑制单核细胞-内皮细胞的相互作用，我们推测，弓抑制动脉粥样硬化形成的影响可能介导的部分NO。方法和结果汇合单层人主动脉内皮细胞暴露于静态或流体弓条件下4小时。更换培养基，然后将细胞与天然LDL（50 μ g/mL）、氧化LDL（30 μ g/mL）或脂多糖（LPS）（10 ng/mL）+肿瘤坏死因子-α（TNF-α）（10 U/mL）再孵育4小时。不降低然后进行使用THP-1单核细胞的结合测定。通过光泽精化学发光监测人主动脉内皮细胞的超氧化物产生，并通过流式细胞术定量粘附分子血管细胞粘附分子-1（VCAM-1）和细胞间粘附分子-1的表达。而天然LDL几乎没有影响，与氧化LDL或LPS/TNF-α孵育显着增加超氧化物的产生，核因子-κ B活性，VCAM-1的表达，和内皮细胞的单核细胞。先前暴露于流体流动抑制这些后遗症暴露于细胞因子或氧化脂蛋白。流体流动的影响似乎是由于部分剪切诱导的NO释放，因为与硝基-L-精氨酸共孵育完全废除这些影响的流量。此外，NO供体PAPA-NONO-ate和8-Br-cGMP（但不是8-Br-cAMP）模仿flow.Conclusions以前暴露于流体弓减少细胞因子或脂蛋白刺激的内皮细胞超氧化物的产生，VCAM-1的表达，和单核细胞结合的影响，弓似乎是由于NO。流量介导的NO依赖性调节的氧化反应性转录可能会影响病变部位。
Background In the arterial tree, regions exposed to reduced shear stress (low and/or disturbed flow) are predisposed to atherogenesis. Fluid flow is a potent stimulus for the release of endothelium-derived nitric oxide (NO). Because NO inhibits monocyte-endothelial cell interaction, we speculated that the effects of Bow in inhibiting atherogenesis might be mediated in part by NO.Methods and Results Confluent monolayers of human aortic endothelial cells were exposed to static or fluid Bow conditions for 4 hours. The medium was replaced, and cells were then incubated with native LDL (50 mu g/mL), oxidized LDL (30 mu g/mL), or lipopolysaccharide (LPS) (10 ng/mL) + tumor necrosis factor-alpha (TNF-alpha) (10 U/mL) for an additional 4 hours. Functional. binding assays using THP-1 monocytes were then performed. Superoxide production by human aortic endothelial cells was monitored by lucigenin chemiluminescence, and expression of the adhesion molecules vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 were quantified by flow cytometry. Whereas native LDL had little effect, incubation with either oxidized LDL or LPS/TNF-alpha significantly increased superoxide production, nuclear factor-kappa B activity, VCAM-1 expression, and endothelial adhesiveness for monocytes. Previous exposure to fluid flow inhibited these sequelae of exposure to cytokines or oxidized lipoprotein. The effect of fluid flow appears to be due in part to shear-induced release of NO, because coincubation with nitro-L-arginine completely abolished these effects of flow. Furthermore, the NO donor PAPA-NONO-ate and 8-Br-cGMP (but not 8-Br-cAMP) mimicked the effects of flow.Conclusions Previous exposure to fluid Bow decreased cytokine- or lipoprotein-stimulated endothelial cell superoxide production, VCAM-1 expression, and monocyte binding; the effects of Bow appear to be due to NO. Flow-mediated NO-dependent regulation of oxidant-responsive transcription may influence the site of a lesion.