Coronary arterial dynamics and atherogenesis

冠状动脉动力学和动脉粥样硬化形成

• 批准号: 6998169
• 负责人: J SCOTT VANEPPS
• 金额: $ 3.4万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6998169
• 关键词: apoptosis; atherosclerosis; biomarker; biomechanics; cell proliferation; computational biology; coronary artery; fluid flow; histology; inflammation; lipids; luminescence; mechanical stress; organ culture; perfusion; predoctoral investigator; shear stress; swine; western blottings

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.

描述（由申请人提供）：虽然动脉粥样硬化（AS）的危险因素本质上是全身性的，但某些动脉（如冠状动脉）比其他动脉更容易患AS。冠状动脉由于被拴在跳动的心脏上而经历了循环弯曲、拉伸和扭曲的额外机械力，这表明剪切和壁应力都是导致AS的原因。假设：与动脉段动态运动相关的局部剪切和壁应力变化影响动脉粥样硬化早期标志物的分布。具体目的：(1)通过实验确定完整动脉段在生理真实的体外灌注条件下（包括循环屈曲、拉伸和扭曲）动脉粥样硬化早期标志物（即内皮损伤、脂质积累和炎症激活）的程度和空间分布；(2)分别利用计算流体力学和计算固体应力分析估算实验灌注动脉段的切应力和壁应力分布；(3)确定计算估计的剪切和壁应力分布与实验确定的动脉粥样硬化终点的空间变化之间的相关关系。