HUMAN LIPOPROTEIN PATHOPHYSIOLOGY

年轻高脂血症受试者中的早产性血管疾病仍是一个 在发病机制和治疗方面尚未解决的重大健康问题。 最近的研究进展导致了用于遗传分析的新标记，新的 脂蛋白代谢与动脉粥样硬化性疾病的研究方法 级数和回归，以及诊断的参考值 高脂血症。有了这些进步，现在就有机会 进一步深入研究脂蛋白生理学和 具有遗传特征的患者的病理生理学研究 了解疾病机制，开发更好的治疗方法，以及 识别和预防早期血管疾病。这将是 通过将我们的注意力集中在分子、遗传和 遗传性脂蛋白异常血症的病理生理基础 患有过早冠状动脉疾病的患者，特别是 家族性混合性高脂血症，家族性中度高胆固醇血症， Lp(A)家族性升高与同型半胱氨酸血症携带者状态 病理生理状态表征的协调研究， 可能的分子生物学缺陷的鉴定和 用统计遗传技术对这些家系的结果进行评估 将在每一种紊乱中执行。蛋白质介导的作用 脂蛋白的血管内修饰及其氧化的作用 每种疾病中的脂蛋白将导致这些疾病的特征 遗传性脂蛋白异常。计划项目，由四个项目组成 协调项目、四个辅助核心设施和一个 多学科调查团队将结合专业知识在 生理学、分子生物学、生物化学、遗传学、免疫化学、 营养学、内分泌学、新陈代谢、流行病学和统计学 遗传学，研究脂蛋白生理学和病理生理学 基础分子生物学和细胞生物学的生物组织水平 从人体体内研究到种群研究。

Premature vascular disease in young hyperlipidemic subjects remains a major unsolved health problem in terms of pathogenesis and treatment. Recent research advances have led to new markers for genetic analysis, new methods for studying lipoprotein metabolism and atherosclerotic disease progression and regression, and reference values for diagnosing hyperlipidemia. With these advances, the opportunity now exists for further in-depth focused studies of lipoprotein physiology and pathophysiology in genetically characterized patients with the objectives of understanding disease mechanisms, developing better treatments, and identifying and preventing early vascular disease. This will be accomplished by focusing our attention on the molecular, genetic and pathophysiological basis of the inherited dyslipoproteinemias associated with premature coronary artery disease with particular reference to familial combined hyperlipidemia, familial moderate hypercholesterolemia, familial elevation of Lp(a) and the carrier state for homocysteinemia. Coordinated studies of characterization of the pathophysiological state, the identification of possible molecular biological defects and the evaluation of these results in families by statistical genetic techniques will be performed in each disorder. The role of protein mediated intravascular modification of lipoproteins and the role of oxidation of lipoproteins in each disorder will lead to characterization of these genetic lipoprotein abnormalities. The Program Project, comprised of four coordinated projects, four supporting core facilities and a multidisciplinary team of investigators will combine the expertise in physiology, molecular biology, biochemistry, genetics, immunochemistry, nutrition, endocrinology, metabolism, epidemiology, and statistical genetics, to study lipoprotein physiology and pathophysiology at several levels of biological organization from basic molecular and cell biology through in vivo studies in humans to studies in populations.