Coronary arterial dynamics and atherogenesis

描述(申请人提供)：虽然动脉粥样硬化(AS)的危险因素本质上是系统性的，但某些动脉(例如冠状动脉)比其他动脉更容易患AS。冠状动脉由于与跳动的心脏相连而经历循环弯曲、伸展和扭转的附加机械力，这表明剪应力和壁应力都是AS的贡献者。假设：与动脉节段动态运动相关的剪切应力和壁应力的局部变化影响动脉粥样硬化形成的早期标志物的分布。具体目标：(1)通过实验确定暴露于周期性弯曲、拉伸和扭转等生理现实体外灌流条件下的完整动脉段动脉粥样硬化形成的早期标志物(即内皮细胞损伤、脂质堆积和炎症激活)的范围和空间分布；(2)利用计算流体力学和计算固体应力分析分别估计每个实验灌流动脉段的切应力和壁应力分布；(3)确定通过计算估计的切应力和壁应力分布与实验确定的致动脉粥样硬化终点的空间变化之间的相关关系。

DESCRIPTION (provided by applicant): Although risk factors for atherosclerosis (AS) are systemic in nature, certain arteries (e.g. coronary arteries) are more susceptible to AS than others. The coronary arteries experience the added mechanical forces of cyclic flexing, stretching and twisting due to their tethering to a beating heart suggesting that both shear and mural stress are contributors to AS. Hypothesis: Local variations in shear and mural stress associated with dynamic motion of arterial segments influence the distribution of early markers of atherogenesis. Specific Aims: (1) Determine experimentally the extent and spatial distribution of early markers (i.e. endothelial injury, lipid accumulation, and inflammatory activation) of atherogenesis in intact arterial segments exposed to physiologically realistic ex vivo perfusion conditions including cyclic flexure, stretch and twist; (2) Estimate the shear and mural stress distributions specifically for each experimentally perfused arterial segment using computational fluid dynamics and computational solid stress analyses, respectively; (3) Determine the correlative relationships between the shear and mural stress distributions estimated computationally and the spatial variation of atherogenic endpoints determined experimentally.