Molecular alterations associated with aneurysmal remodeling are localized in the high hemodynamic stress region of a created carotid bifurcation.
Molecular alterations associated with aneurysmal remodeling are localized in the high hemodynamic stress region of a created carotid bifurcation.
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DOI：
10.1227/01.neu.0000343541.85713.01
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发表时间：
2009-07
期刊：
影响因子：
4.8
通讯作者：
Meng H
中科院分区：
文献类型：
--
作者：
Wang Z;Kolega J;Hoi Y;Gao L;Swartz DD;Levy EI;Mocco J;Meng H
尽管推测血流动力学升高在颅内动脉瘤（IA）的发生中起关键作用，但对触发颅内血管退化的特定血流动力学微环境知之甚少。我们先前证明了IA启动的适应不良重塑特征发生在实验创建的颈动脉分叉尖端附近的高壁切应力（WSS）和高WSS梯度相结合的血流动力学区域。本研究探讨了这种重塑是否重现了IA中发现的分子变化，以及分子变化是否也对应于特定的血流动力学环境。在6只犬的每一只中，使用两个自体颈总动脉手术创建从头分叉。手术后2周或2个月通过高分辨率三维血管造影术对分叉进行成像，通过计算流体动力学模拟获得流场。随后，对采集的组织进行白细胞介素-1 β、内皮细胞和诱导型一氧化氮合酶、硝基酪氨酸和基质金属蛋白酶-2和-9免疫染色，显示心尖附近的早期囊性变化。将分子的空间分布与计算流体力学结果进行了比较。与周围节段、供血动脉和天然对照相比，动脉瘤壁显示内皮型一氧化氮合酶表达降低，而所有其他标志物均升高。抗-CD 68染色表明在囊壁中不存在炎性细胞。比较分子标记物分布与流场揭示了这些分子变化在高WSS和高正WSS梯度的血流动力学区域内的局限性。高WSS和高正WSS梯度联合诱导的动脉瘤起始重塑与IA相关的分子变化相关。
Although elevated hemodynamics has been speculated to play a key role in intracranial aneurysm (IA) initiation, little is known about the specific hemodynamic microenvironment that triggers aneurysmal vascular degradation. We previously demonstrated maladaptive remodeling characteristic of IA initiation occurring in hemodynamic regions of combined high wall shear stress (WSS) and high WSS gradient near the apex of an experimentally created carotid bifurcation. This study examines whether this remodeling recapitulates the molecular changes found in IAs and whether molecular changes also correspond to specific hemodynamic environments. De novo bifurcations were surgically created using both native common carotid arteries in each of 6 dogs. Bifurcations were imaged 2 weeks or 2 months after surgery by high-resolution 3-dimensional angiography, from which flow fields were obtained by computational fluid dynamics simulations. Subsequently, harvested tissues, demonstrating early aneurysmal changes near the apex, were immunostained for interleukin-1β, endothelial and inducible nitric oxide synthases, nitrotyrosine, and matrix metalloproteinase-2 and -9. Spatial distributions of these molecules were comapped with computational fluid dynamics results. The aneurysmal wall showed decreased endothelial nitric oxide synthase expression compared with surrounding segments, the feeding artery, and native controls, whereas all other markers increased. Anti-CD68 staining indicated the absence of inflammatory cells in the aneurysmal wall. Comapping molecular marker distributions with flow fields revealed confinement of these molecular changes within the hemodynamic region of high WSS and high, positive WSS gradient. Aneurysm-initiating remodeling induced by combined high WSS and high, positive WSS gradient is associated with molecular changes implicated in IAs.