ROLE OF THE ARTERIAL WALL IN ATHEROSCLEROSIS

动脉壁在动脉粥样硬化中的作用

• 批准号: 3097477
• 负责人: WILLIAM HOLLANDER
• 金额: $ 162.85万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-09-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3097477
• 关键词: atherosclerosis; hypertension; vascular smooth muscle

The object of the program project is to enhance the understanding of the pathogenesis of hypertensive and atherosclerotic vascular disease particularly of the coronary and cerebral vessels. In achieving the objective, studies are being conducted in nonhuman primate models (cynomolgus monkey) with experimental atherosclerosis and/or hypertension and in tissue culture models using smooth muscle cells and macrophages. Atherosclerosis in the monkey is produced by surgically coarcting the thoracic aorta. The specific aims of the program are to determine (1) the effects of hypercholesterolemic atherogenic diet and/or hypertension on the levels of circulating immune complexes in the cynomolgus monkey; (2) the participation of immunological factors in atherosclerosis and its aggravation by hypertension by correlating the immunological findings in the blood vessels and circulation with the extent and severity of the experimentally induced vascular disease; (3) whether the lipid-protein complexes contained in human atherosclerotic plaques are autoimmune complexes consisting of apolipoproteins and anti-apolipoprotein antibodies; (4) effects of atherosclerosis and hypertension on collagen gene expression in the cynomolgus monkey aortic tissue; (5) the production of Type I and II collagen protein and the processing elastin synthesis, secretion and accumulation in vascular smooth muscle cells; (6) the nature of the mechanisms of control of the biosynthetic pathway in which lysyl oxidase is synthesized in cultured aortic smooth muscle cells (SMC); (7) the steroid specificity of the control levels of lysyl oxidase activity in cultured SMC; (8) the biosynthesis of the connective tissue components during the course of matrix development in response to matrix injury; (9) the effect of proteolytic or mechanical injury to SMC culture with respect to the regulation of Type I and Type III collagen genes and cell proliferation; (10) secretory and phagocytic function of the smooth muscle cell derived foam cell. The use of non-human primate models as well as tissue culture models is believed to represent an important and effective approach to the study of vascular disease at the tissue, cellular and molecular level.

该项目的目的是加强对 高血压和动脉粥样硬化血管的发病机制 特别是冠状动脉和脑血管的疾病。 在 为了实现这一目标，目前正在非人类 实验性灵长类动物模型（食蟹猴） 动脉粥样硬化和/或高血压以及组织培养模型 使用平滑肌细胞和巨噬细胞。 动脉粥样硬化 猴子是通过外科手术缩窄胸主动脉而产生的。 该计划的具体目标是确定（1）影响 高胆固醇血症致动脉粥样硬化饮食和/或高血压 食蟹猴中循环免疫复合物的水平 猴;（2）免疫因子参与 动脉粥样硬化及其由高血压引起的加重 血管和循环中的免疫学发现 与实验诱导的 血管疾病;（3）脂质-蛋白质复合物是否 动脉粥样硬化斑块中含有自身免疫性 由载脂蛋白和抗载脂蛋白组成的复合物 抗体;（4）动脉粥样硬化和高血压对 食蟹猴主动脉组织中胶原基因的表达; (5)I型和II型胶原蛋白的产生， 处理弹性蛋白的合成、分泌和积累， 血管平滑肌细胞;（6）的机制的性质， 赖氨酰氧化酶的生物合成途径的控制 在培养的主动脉平滑肌细胞（SMC）中合成;（7） 赖氨酰氧化酶活性对照水平的类固醇特异性 （8）结缔组织的生物合成 在矩阵开发过程中， （9）蛋白水解或机械损伤的影响 关于I型和II型的调节， III型胶原基因与细胞增殖;（10）分泌型和 平滑肌细胞衍生的泡沫细胞的吞噬功能。 使用非人灵长类动物模型以及组织培养 模型被认为是一种重要而有效的 从组织、细胞和免疫学角度研究血管疾病 分子水平。