BIOENGINEERING-BIOLOGICAL STUDY OF ARTERIAL DISEASE

提出了一项多学科研究项目，以调查 血流动力学在动脉疾病发展中的作用。具体地说，各种 生物工程、生物化学、外科、细胞等领域的学科 生物学和兽医病理学将结合在一起的综合方法 来研究这个复杂的问题。我们研究工作的一个新特点是 脉冲复制器(PDA)用于体外模拟 逼真的血管血流动力学。掌上电脑的设计使得 个体血流动力学变量的相对重要性，如平均值 压力、脉压、脉率、流率和跨壁压力 动脉壁对脂蛋白分子的摄取和分布 可以被描绘出来。 脂蛋白壁转运的实验结果将被解释并 与伴随测量和详细计算相关联 细胞骨架的脂质生物化学、组织学、荧光显微镜 内膜肌动蛋白和肌球蛋白阵列，生理流体力学，以及 胆固醇摄取的数学模型。细胞生物学的数据是 对我们的长期目标很重要，那就是加深对 血流动力学和动脉疾病，因为细胞骨架阵列 收缩蛋白似乎对维持内膜很重要 活体内的完整性。 总之，申请者打算进行灌流实验，实验室 一个为期三年的项目的测量和生物工程分析。我们的 建议得到上述各项初步数据的支持 纪律。希望拟议项目的结果将是 提供有关各种血液动力学影响的新信息 哺乳动物血管中胆固醇沉积的模式有助于 致动脉粥样硬化斑块。

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.