PATHOBIOLOGICAL DETERMINANTS OF ATHEROSCLEROSIS IN YOUTH

青年动脉粥样硬化的病理学决定因素

• 批准号: 3433060
• 负责人: ABEL L ROBERTSON
• 金额: $ 15.49万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-06-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3433060
• 关键词: adolescence (12-20); atherosclerosis; autoradiography; blood lipoprotein; cardiovascular disorder epidemiology; cardiovascular infection; cell type; cooperative study; disease /disorder proneness /risk; electron microscopy; gel electrophoresis; gender difference; glycoproteins; histochemistry /cytochemistry; human subject; humoral immunity; immune complex; immunochemistry; immunofluorescence technique; immunoperoxidase; monoclonal antibody; nucleic acid probes; organ culture; pathology; postmortem; protein structure; scanning electron microscopy; serology /serodiagnosis; surface antigens; tissue /cell culture; tissue /cell preparation; virus antigen; virus classification; young adult human (21-34)

The major purpose of this investigator-initiated multicenter cooperative study is to answer, utilizing modern pathobiological approaches, some key questions concerning the pathogenesis of human atherosclerosis in the USA. Aortas and coronary arteries from 15-35 years old males and females from multiple study sites will be examined to determine detailed characteristics of arterial changes observed in late childhood which may suggest potential progression to lesions commonly found in young adults. Our proposal will address these objectives by systematically evaluating a large number of coronary arteries and aortas from young persons succumbing suddenly and unexpectedly from accidental causes. Under standardized conditions, isolated fatty streaks, transitional lesions and fibrous plaques will be examined for 1) protein composition and lesion distribution of specific lipoproteins and glycosoaminoglycans in intimal lesions as well as in isolated arterial cells utilizing two-dimensional electrophoresis combined with immunospecific staining with monoclonal antibodies and peroxidase labeled lectins; 2) identification of cells found in each lesion type will be carried out using specific surface membrane markers, by the detection of humoral immune components at lesion sites with monospecific antibodies and by evaluating the role of immune complexes on lesion development 3) detection of viral antigens at lesion sites by immunohistological methods as well as in situ nucleic acid hybridization technology will be used to evaluate the potential role of viruses and/or their genomes known to produce latent or persistent infections on the initiation and/or progression to advanced atheroma; and 4) by developing probability maps for each age group of the occurrence of specific type lesions, attempts will be made to define average topological loci in relation to lesion severity, sex or race comparing lesion-prone vascular segments with those found to have low probability to develop atheroma in each age group. It is believed that such information, combined with those of the other centers participating in the overall USA protocol should provide much needed information regarding the evolution of the early stages of human atherogenesis as well as their potential clinical significance.

该研究者发动的多中心合作社的主要目的 研究是要回答，利用现代病理学方法，一些关键 关于美国动脉粥样硬化发病机理的问题。 主动脉和冠状动脉的15-35岁男性和女性 将检查多个研究地点以确定详细的特征 儿童后期观察到的动脉变化可能表明潜力 进展到年轻人常见的病变。 我们的建议将通过系统地评估 来自年轻人的大量冠状动脉和主动脉屈服 突然出乎意料地出于意外原因而出乎意料。 在标准化之下 条件，孤立的脂肪条纹，过渡性病变和纤维 将检查斑块的蛋白质组成和病变分布 内膜病变中的特定脂蛋白和糖胺聚糖也 就像在使用二维电泳的孤立动脉细胞中一样 与单克隆抗体和 过氧化物酶标记的凝集素； 2）鉴定每个病变中发现的细胞 类型将使用特定的表面膜标记进行 在具有单特异性的病变部位检测体液免疫成分 抗体并评估免疫复合物在病变上的作用 开发3）通过通过病变位点检测病毒抗原 免疫组织学方法以及原位核酸杂交 技术将用于评估病毒和/或 他们已知会在该基因组上产生潜在或持续感染 启动和/或向晚期动脉瘤进展； 4）开发 特定类型的每个年龄段的概率图 病变，将尝试定义平均拓扑基因座 与病变的严重程度，性别或种族有关，比较容易病变的血管 发现患有障碍障碍的细分市场 每个年龄段。 据信，这些信息与这些信息相结合 参加整个美国协议的其他中心应 提供有关早期演变的急需信息 人类动脉粥样硬化及其潜在的临床意义。