SPECIALIZED CENTER OF RESEARCH IN ARTERIOSCLEROSIS

这是一个紧密结合的计划，深入研究 脂蛋白相互作用和与各种细胞， 以及脂蛋白是如何产生和获得的 进入并积聚在动脉壁，影响细胞 新陈代谢. 个体恒河猴是我们许多研究的焦点， 问题研究 将在几个层次上处理这些核心问题， 单个脂蛋白和脂蛋白的结构和相互作用 亚类;其组分脱辅基蛋白的异质性;体内 以及脱辅基蛋白和脂蛋白的体外形成和代谢， 肝脏、肠和血浆隔室内;控制 新生极低密度脂蛋白的组装和细胞内转运的因子， 血浆低密度脂蛋白的前体; 脂蛋白谱在体内强调的差异反应 个体动物进行高脂肪挑战，特别注意 这些的分子基础;相互作用的特异性决定因素 脂蛋白和脂蛋白亚类与动脉壁细胞 和肝脏;脂蛋白和脂蛋白亚类对 平滑肌细胞和巨噬细胞在组织培养;的影响， 血液动力学因素在调节脂蛋白对动脉粥样硬化的影响中的作用 动脉壁和培养细胞上;脂蛋白大小的决定因素 在正常和高脂血症动物中。 主要强调的是 脂蛋白和脱辅基蛋白的主要类别内的异质性， 无论这些是由遗传、营养和生物合成控制的， 其他代谢决定因素。

This is a closely integrated program which intensively investigates lipoprotein interactions with one another and with various cells and tissues of the body, as well as how lipoproteins are produced and gain access to and accumulate in the artery wall, there to affect the cell metabolism. The individual Rhesus monkey is the focus of many of our studies. These central concerns will be approached at several levels--the structure and the interactions of individual lipoproteins and lipoprotein subclasses; the heterogeneity of their component apoproteins; the in vivo and in vitro formation and metabolism of apoproteins and lipoproteins by the liver, the intestine and within the plasma compartment; the controlling factors in the assembly and intracellular transport of nascent VLDL, the precursor of plasma LDL; the familial and nutritional determinants of lipoprotein profiles in vivo emphasizing the differential response of individual animals to high fat challenge with particular attention to the molecular basis of these; the specificity determinants of the interaction of lipoproteins and lipoprotein subclasses with cells of the artery wall and liver; the effects of lipoproteins and lipoprotein subclasses on the smooth muscle cells and macrophages in tissue culture; the effects of hemodynamic factors in modulating the influence of lipoproteins on the artery wall and on cells in culture; the determinants of lipoprotein size in normal and hyperlipidemic animals. Major emphasis is given to the heterogeneity within the major classes of lipoproteins and apoproteins, whether these are controlled by genetic, nutritional, and biosynthetic or other metabolic determinants.