PATHOBIOLOGICAL DETERMINANTS OF ATHEROSCLEROSIS IN YOUTH

总的目标是通过数字荧光来确定 3-脂质包涵体、巨噬细胞和平滑 人体左前肌解剖学上定义的节段中的肌细胞 冠状动脉降支 数量的变化，相对 这些血管壁成分的比例和空间分布， 动脉粥样硬化的年龄依赖性退行性变化的功能是 没有充分记录。 要想推断出其分布，需要图像分析的客观性。 脂质包涵体和原位特异性细胞。 计算机分析表明， 特定荧光强度值的比率，在不损失 通过光漂白发信号将允许在逐像素基础上进行比较 并且用于连续的图像平面。 细胞之间的关系， 细胞外成分及其参与的表观进展 脂肪条纹与纤维动脉粥样硬化斑块的关系可通过计算机进行分析 以前没有的方法。 这些研究将试图 回答具体问题。 (1)动脉内膜损伤是晚期 儿童期（脂肪条纹）进展为病变，在成年期， 与动脉闭塞和缺血性疾病（纤维性 斑块）？ 在什么年龄、什么条件下出现"过渡性"病变 (that具有脂肪条纹和 纤维斑块）发生？ (2)如果（1）中假设的进展确实发生， 最早可检测到的脂肪条纹的变化，表明这一点 进展？ 更具体地说，脂质中是否存在脂质体， 脂蛋白组成和位置，内皮覆盖，纤维蛋白和 血小板定位，单核细胞/巨噬细胞/泡沫细胞群，平滑 肌细胞数量或结构、微量元素和电解质组成， 或脂肪条纹的结缔组织成分， 发展成纤维斑块，相比之下， 有可能取得进展吗？

The overall goal is to determine, by digitial fluorescence, the 3-dimensional distribution of lipid inclusions, macrophages and smooth muscle cells in the in anatomically defined segments of human left anterior descending coronary artery. Changes in the number, the relative proportions and the spatial distribution of these vessel wall components as a function of the age-dependent degenerative changes of atherosclerosis are not adequately documented. The objectivity of image analysis is needed to deduce the distribution of lipid inclusions and specific cells in situ. A computer analysis of the ratio of specific fluorescence intensity values, acquired without loss of signal by photobleaching, will allow comparisons on a pixel by pixel basis and for successive image planes. The relationships between cells and extracellular components and their involvement in the apparent progression of fatty streaks to fibroatheromatous plaques can be analyzed by computer based methods not previously available. These studies will attempt to answer the specific questions. (1) Do the arterial intimal lesions that are characteristic of later childhood (fatty streaks) progress into the lesions that, in adulthood, are closely associated with arterial occlusion and ischemic disease (fibrous plaques)? At what age and under what conditions to "transitional" lesions (that is, lesions that have characteristics of both fatty streaks and fibrous plaques) occur? (2) If the progression hypothesized in (1) does take place, what are the earliest detectable changes in the fatty streak that indicate this progression? More specifically, are there differeces in the lipid or lipoprotein composition and location, endothelial covering, fibrin and platelet localization, monocyte/macrophage/foam cell population, smooth muscle cell number or structure, trace element and electrolyte composition, or connective tissue composition of the fatty streaks which are most likely to progress to fibrous plaques, as compared to fatty streaks which are not likely to progress?