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: 3433063
• 负责人: FREDERICK J CORNHILL
• 金额: $ 13.47万
• 依托单位: OHIO STATE UNIVERSITY
• 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/3433063
• 关键词: adolescence (12-20); atherosclerosis; biomedical facility; cardiovascular disorder epidemiology; cooperative study; disease /disorder proneness /risk; human subject; image processing; microscopy; morphology; pathology; postmortem; tissue /cell preparation; young adult human (21-34)

This is a 4-phase, investigator initiated, multicenter study. Its major purpose is to study important unanswered questions concerning the pathogenesis of human atherosclerosis using modern pathobiological approaches. To accomplish this, autopsies on persons (15-35 yr) killed by trauma will be done under rigorously controlled protocols to supply specified tissue samples for standardized biochemical and morphologic studies. The morphometric and biochemical analysis will be performed at designated Central Laboratories; these are: histotechnique (Univ of Chicago), morphometry (Ohio State Univ), and lipid biochemistry (Louisiana State Univ, New Orleans). The study design and all of the statistical aspects of the common protocol sections of the study, including the analysis of a major portion of the data, will be accomplished in the Central Statistical and Data Analysis Laboratory in San Antonio. The Central Laboratory at LSU will organize the data on risk factors from each case and will do most of the analyses on the post-mortem samples of blood. In this application the role of the Ohio State Univ in specimen collection and the activity of the Morphometry Central Laboratory (MCL) are presented. The Ohio State Univ will contribute 125 sets of specimens per year to the multicenter study. The MCL will analyze over 100,000 microscopic and macroscopic images generated in the study. The MCL will produce tabular data (e.g., lesion thickness) and spatial data (e.g., probability-of-occurrence maps). Among the major questions being addressed using data from the morphometry center are: 1) Do some fatty streaks progress to fibrous plaques and, if so, can the morphological characteristics of a transitional lesion be defined? 2) What is the evolutionary patter of different lesion types with increasing age? 3) What are the morphometric changes associated with progression? 4) What are the incidence and morphologic features of insudative (gelatinous) lesions and does the probability-of-occurrence map for these correlate with that of subsequent proliferative disease? 5) What structural features of lesions can be correlated with specific risk factors? 6) Are there morphometric differences in lesion structure between sexes that can account for the well-known differences in clinical course? 7) Do atherosclerotic structural features or risk factors data for young people provide any insight into the decline of coronary heart disease in the United States?

这是一项由研究者发起的四阶段多中心研究。 其主要 目的是研究有关重要的未解答的问题 现代病理生物学研究人类动脉粥样硬化的发病机制 接近。 为了实现这一目标，对被杀害的人（15-35 岁）进行尸检 创伤将在严格控制的协议下进行 用于标准化生化和形态学的指定组织样本 研究。 形态测定和生化分析将在 指定的中心实验室；这些是： 组织技术（Univ of 芝加哥）、形态测量学（俄亥俄州立大学）和脂质生物化学（路易斯安那州） 新奥尔良州立大学）。 研究设计和所有统计数据 研究的共同方案部分的各个方面，包括 大部分数据的分析将在 圣安东尼奥中央统计和数据分析实验室。 这 路易斯安那州立大学中心实验室将整理各个领域的风险因素数据 并将对尸检血液样本进行大部分分析。 在此应用中，俄亥俄州立大学在标本采集中的作用 形态测量中心实验室（MCL）的活动是 提出。 俄亥俄州立大学将每年贡献 125 套标本 多中心研究的一年。 MCL 将分析超过 100,000 研究中生成的微观和宏观图像。 MCL 将 生成表格数据（例如病变厚度）和空间数据（例如 发生概率图）。 正在解决的主要问题之一 使用来自形态测量中心的数据是：1）做一些脂肪条纹 进展为纤维斑块，如果是这样，形态学可以 过渡性病变的特征如何定义？ 2）什么是 随着年龄的增长，不同病变类型的进化模式？ 3）什么 形态变化与进展相关吗？ 4）有哪些 渗出性（凝胶状）病变的发生率和形态特征以及 这些的发生概率图与 随后的增殖性疾病？ 5）病变有哪些结构特点 可以与特定的风险因素相关吗？ 6）是否有形态测量 性别之间病变结构的差异可以解释 临床过程中众所周知的差异？ 7）做动脉粥样硬化 年轻人的结构特征或危险因素数据提供了任何 洞察美国冠心病发病率下降情况？