Shear stress affects the intracellular distribution of eNOS: direct demonstration by a novel in vivo technique
Shear stress affects the intracellular distribution of eNOS: direct demonstration by a novel in vivo technique
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DOI：
10.1182/blood-2005-06-2326
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发表时间：
2005-12-01
期刊：
影响因子：
20.3
通讯作者：
Krams, R
中科院分区：
文献类型：
--
作者：
Cheng, C;van Haperen, R;Krams, R
动脉粥样硬化在血管树中的病灶位置与切应力的局部变化相关。我们开发了一种方法，以诱导确定的变化，在小鼠的直血管段的剪切应力。为此，在颈动脉周围放置具有锥形内腔的圆柱体，诱导高剪切应力场。同时，在装置的上游和下游分别产生低剪切应力和振荡剪切应力区域。该装置用于eNOS 3GFP融合基因转基因小鼠。我们观察到与其他区域相比，在高切应力区域，内皮型一氧化氮合酶-绿色荧光蛋白（eNOS-GFP）mRNA的表达被强烈诱导（P <0.05）。eNOS-GFP荧光定量或高尔基复合体或血小板内皮细胞粘附分子1（PECAM-1）的免疫反应性显示，与未处理的颈动脉相比，高切应力区增加（P <0.05）。eNOS-GFP与高尔基体复合体或PECAM-1的共定位也对剪切应力的改变作出反应。总之，我们表明，在体内的mRNA和蛋白质表达的直接响应诱导的剪切应力的变化。该模型为研究剪切应力改变、基因表达和动脉粥样硬化之间的关系提供了机会。
The focal location of atherosclerosis in the vascular tree is correlated with local variations in shear stress. We developed a method to induce defined variations in shear stress in a straight vessel segment of a mouse. To this end, a cylinder with a tapered lumen was placed around the carotid artery, inducing a high shear stress field. Concomitantly, regions of low shear stress and oscillatory shear stress were created upstream and downstream of the device, respectively. This device was used in mice transgenic for an eNOS3GFP fusion gene. We observed a strong induction of endothelial nitric oxide synthase-green fluorescent protein (eNOS-GFP) mRNA expression in the high shear stress region compared with the other regions (P < .05). Quantification of eNOS-GFP fluorescence or of immunoreactivity to the Golgi complex or to platelet endothelial cell adhesion molecule 1 (PECAM-1) showed an increase in the high shear stress region (P < .05) compared with nontreated carotid arteries. Colocalization of eNOS-GFP with either the Golgi complex or PECAM-1 also responded to alterations of shear stress. In conclusion, we showed a direct response of mRNA and protein expression in vivo to induced variations of shear stress. This model provides the opportunity to study the relationship between shear stress alterations, gene expression, and atherosclerosis.