Core C: Computational and Experimental Biomechanical Assessment (CEBA)

计算和实验生物力学评估(CEBA) 核心C--项目摘要 这一科学核心将在体内和体内提供一致和全面的生物力学评估 本计划项目中使用的不同小鼠模型的体外实验。首先，小鼠特有的主动脉几何结构将 将使用MicroCT来确定，而相关的进出口流量和入口压力将被测量 在活体内分别使用超声波和米勒压力导管。第二，圆柱形试件将 从升主动脉、降主动脉、肾上段和肾下段切除，并接受 新的，一致的，体外生物力学表型。具体地说，我们将评估内皮依赖和 独立的血管扩张能力，诱导的双轴平滑肌细胞收缩能力的受损水平，以及 被动双轴力学性能，我们将跨区域和组使用 适当的参数和非参数统计。第三，双轴材料特性将被用于 计算区域材质和结构刚度、储能和特定于层的墙应力，其中 结合显微CT和其他活体数据，将形成独特的流固相互作用计算 可以评估改变的几何形状和壁属性对微观机械的影响的模拟 每种主要细胞类型所处的环境(例如，内皮剪应力和光滑 肌肉和成纤维细胞壁内应力)。这些结果将依次提供给四个项目中的每一个 在整个计划项目中，实现机械刺激与来自无数结果的关联 在每个项目中使用的生物检测。这样，我们将第一次能够集体评估， 细胞机械感觉和细胞外基质的机械调节的关键作用 胸主动脉的顺应性和强度，当受损时，会导致结构完整性的丧失 这表现为一种潜在的致命的胸主动脉瘤。

COMPUTATIONAL AND EXPERIMENTAL BIOMECHANICAL ASSESSMENT (CEBA) CORE C - PROJECT SUMMARY This Scientific Core will provide consistent and comprehensive biomechanical evaluation, both in vivo and in vitro, of the different mouse models used in this Program Project. First, mouse-specific aortic geometries will be determined using microCT whereas associated inlet and outlet flows and inlet pressures will be measured in vivo using ultrasound and Millar pressure catheters, respectively. Second, cylindrical specimens will be excised from the ascending, descending, suprarenal, and infrarenal segments of the aorta and subjected to novel, consistent, in vitro biomechanical phenotyping. Specifically, we will assess endothelial-dependent and independent vasodilatory capacity, compromised levels of induced biaxial smooth muscle cell contractility, and passive biaxial mechanical properties, and we will compare results across regions and groups using appropriate parametric and non-parametric statistics. Third, the biaxial material properties will be used to compute regional material and structural stiffnesses, energy storage, and layer-specific wall stresses, which in conjunction with the microCT and other in vivo data will inform unique fluid-solid-interaction computational simulations that can assess effects of altered geometry and wall properties on the micro-mechanical environment to which each of the primary cell types is exposed (e.g., endothelial shear stresses and smooth muscle and fibroblast intramural stress). These results, in turn, will be provided to each of the four Projects within the overall Program Project to enable correlations of mechanical stimuli with results from the myriad biological assays used in each project. In this way, collectively we will be able to evaluate, for the first time, critical roles of cellular mechanosensing and mechanoregulation of the extracellular matrix that endows the thoracic aorta with its compliance and strength and when compromised results in the loss of structural integrity that manifests as a potentially lethal thoracic aortic aneurysm.