BIOENGINEERING-BIOLOGICAL STUDY OF ARTERIAL DISEASE

动脉疾病的生物工程生物学研究

• 批准号: 3348003
• 负责人: HARVEY S. BOROVETZ
• 金额: $ 14.75万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1988-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3348003
• 关键词: artery occlusion; atherosclerosis; blood lipoprotein transport; carotid artery; catalase; cholesterol; cholesterol esters; fluorescence microscopy; hemodynamics; lysophospholipase; mathematical model; model design /development; perfusion; radiotracer; scanning electron microscopy; tissue /cell culture

A multidisciplinary research project is proposed to investigate the role of hemodynamics in the development of arterial disease. Specifically, various disciplines in the areas of bioengineering, biochemistry, surgery, cell biology and veterinary pathology will be joined in an integrated approach to study this complex problem. A novel feature of our research effort is the use of a pulse duplicator apparatus (PDA) for simulation in vitro of realistic vascular hemodynamics. The PDA has been so designed that the relative importance of individual hemodynamic variables such as mean pressure, pulse pressure, pulse rate, flow rate, and transmural pressure to the uptake and distribution of lipoprotein molecules by the arterial wall can be delineated. Experimental results of lipoprotein wall transport will be interpreted and correlated along with companion measurements and detailed calculations of lipid biochemistry, histology, fluorescence microscopy of the cytoskeletal array of intimal actin and myosin, physiological fluid mechanics, and mathematical models of cholesterol uptake. The data of cell biology are important to our long-term objective of furthering current understanding of hemodynamics and arterial disease, since the cytoskeletal array of contractile proteins appears to be important for maintenance of intimal integrity in vivo. In all, the applicants intend to conduct perfusion experiments, laboratory measurements, and bioengineering analyses for a three-year project. Our proposal is supported by preliminary data in the various aforementioned disciplines. It is hoped that the results of the proposed project will provide new information regarding the effects of various hemodynamic patterns on cholesterol deposition in mammalian vessels contributing to atherogenic plaque.

一个多学科的研究项目，提出了调查的作用， 血液动力学在动脉疾病发展中的作用 具体而言，各种 生物工程、生物化学、外科学、细胞学等学科 生物学和兽医病理学将结合在一个综合的方法 来研究这个复杂的问题。 我们研究工作的一个新特点是 使用脉冲复制器装置（PDA）体外模拟 真实的血管血流动力学。 PDA的设计使得 个体血流动力学变量的相对重要性，例如平均值 压力、脉压、脉率、流速和跨壁压， 动脉壁对脂蛋白分子的摄取和分布 可以被描绘出来。 将解释脂蛋白壁转运的实验结果， 相关的沿着与同伴的测量和详细的计算 脂质生化、组织学、细胞骨架荧光显微镜检查 内膜肌动蛋白和肌球蛋白阵列，生理流体力学， 胆固醇摄取的数学模型。 细胞生物学的数据是 这对我们促进目前对 血液动力学和动脉疾病，因为细胞骨架阵列 收缩蛋白似乎对维持内膜的 体内的完整性。 总之，申请人打算进行灌注实验、实验室研究、生物学实验和生物化学实验。 测量和生物工程分析，为期三年的项目。 我们 该建议得到了上述各种初步数据的支持 学科 希望拟议项目的结果将 提供了关于各种血流动力学影响的新信息， 哺乳动物血管中的胆固醇沉积模式 致动脉粥样硬化斑块