PATHOBIOLOGICAL DETERMINANTS OF ATHEROSCLEROSIS IN YOUTH

总体目标是通过数字荧光来确定 脂质包裹体、巨噬细胞和光滑细胞的三维分布 人体左前叶解剖定位节段内的肌细胞 冠状动脉下行。数字的变化，相对的 这些血管壁组分的比例和空间分布 与年龄相关的动脉粥样硬化退行性改变的一个功能是 没有充分的记录。 需要图像分析的客观性来推断图像的分布 原位可见脂质包涵体和特定细胞。一种计算机分析的方法 在没有损失的情况下获得的特定荧光强值的比率 通过光漂白的信号，将允许逐个像素的比较 并且对于连续的图像平面。细胞与细胞之间的关系 细胞外成分及其在表观进展中的作用 从脂肪条纹到纤维动脉粥样斑块都可以用计算机进行分析 基于以前不可用的方法。这些研究将试图 回答具体问题。 (1)动脉内膜病变是晚期的特征吗？ 儿童期(脂肪条纹)进展为病变，成年后 与动脉闭塞和缺血性疾病(纤维性)密切相关 斑块)？在什么年龄和什么条件下进行“过渡性”损伤 (即，同时具有脂肪条纹和 纤维斑块)？ (2)如果(1)中假设的进展确实发生了，那是什么？ 脂肪条纹中最早可检测到的变化表明这一点 进展？更具体地说，在血脂或 脂蛋白组成和位置，内皮细胞覆盖物，纤维蛋白和 血小板定位，单核/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最有可能 进展为纤维斑块，而不是脂肪条纹 有可能进步吗？

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?