Coronary arterial dynamics and atherogenesis

描述（由申请人提供）：尽管动脉粥样硬化（AS）的风险因素本质上是全身性的，但某些动脉（例如冠状动脉）比其他动脉更易患AS。由于冠状动脉与跳动的心脏相连，冠状动脉会经历周期性弯曲、拉伸和扭曲的附加机械力，这表明剪切应力和壁应力都是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）通过实验确定早期标记的范围和空间分布在暴露于生理学上真实的离体灌注条件（包括循环弯曲、拉伸和扭曲）的完整动脉段中动脉粥样硬化形成（即内皮损伤、脂质积聚和炎症活化）;（二）使用计算流体动力学估计每个实验灌注动脉段的剪切应力和壁应力分布（3）确定计算估计的剪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.