HUMAN LIPOPROTEIN PATHOPHYSIOLOGY

人类脂蛋白病理生理学

• 批准号: 3098162
• 负责人: JOHN J ALBERS
• 金额: $ 181.65万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-05-01 至 1988-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3098162
• 关键词: apolipoproteins; atherosclerosis; blood lipoprotein metabolism; blood lipoprotein transport; cholesterol esters; coronary disorder; dietary lipid; familial hyperlipoproteinemia type I; familial hyperlipoproteinemia type II; high density lipoproteins; hypertriglyceridemia; lecithin cholesterol acyltransferase deficiency; lipid metabolism; low density lipoprotein

Premature vascular disease in young hyperlipidemic subjects remains a major unsolved health problem in terms of pethogenesis and treatment. Recent research has made available reference values for diagnosing hyperlipidemia, markers for genetic analysis, and methods for studying lipoprotein metabolism and arteriosclerotic disease progression. With these advances, the opportunity now exists for in depth, focused studies of lipoprotein pathophysiology in genetically characterized patients toward the objective of understanding disease mechanisms and developing better treatments. This program in "Human Lipoprotein Pathophysiology" siezes this opportunity with 8 coordinated projects and 4 supporting core laboratories led by experienced investigators, experts in physiology, genetics, biochemistry, immunochemistry, metabolism nutrition, and cardiology. Subjects will be characterized in terms of the heritability of lipoprotein abnormalities, the metabolism of lipoproteins, including carefully characterized subpopulations of HDL isolated by immunoabsorption. The role of LCVAT and lipid transfer proteins in the genetic hyperlipidemics will be studied and related to the kinetic abnormalities of lipoprotein metabolism in vivo. The fate of lipoproteins will be studies in human cultured macrophages and placental trophoblast cells and will further the understanding the role of macrophages and steroid hormone secreting cells in lipoprotein homeostasis and atherosclerosis. The effects of diet and drug interventions will also be studied including the effects of omega-3 fatty acid feeding on lipoprotein lipid metabolism and effects of diet and drug lowering of lipoprotein on arteriosclerosis. This work will be supported by excellent Core facilities in lipoprotein measurement, apoprotein immunoassay, and biomathematical analysis and offers promise of rapid progress in understanding mechanisms and providing treatrment for the premature vascular diseade associated with genetic hyperlipidemia.

年轻高血压患者的早发性血管疾病仍然是一个主要的 在发病和治疗方面尚未解决的健康问题。 最近 研究已经提供了诊断高脂血症的参考值， 用于遗传分析的标记和研究脂蛋白的方法 代谢和动脉炎疾病进展。 有了这些进步， 现在有机会对脂蛋白进行深入、集中的研究， 遗传特征患者的病理生理学 了解疾病机制和开发更好的治疗方法。 这 “人类脂蛋白病理生理学”项目抓住了这个机会， 牵头的8个协调项目和4个支持核心实验室 经验丰富的研究人员，生理学，遗传学，生物化学专家， 免疫化学、代谢营养学和心脏病学。 受试者将 其特征在于脂蛋白异常的遗传性， 脂蛋白的代谢，包括仔细表征 通过免疫吸收分离的HDL亚群。 LCVAT的作用和 将研究遗传性高脂血症中的脂质转移蛋白， 与体内脂蛋白代谢的动力学异常有关。 脂蛋白的命运将在人类培养的巨噬细胞中进行研究， 胎盘滋养层细胞，并将进一步了解的作用， 巨噬细胞和类固醇激素分泌细胞在脂蛋白稳态中的作用 和动脉粥样硬化。 饮食和药物干预的效果也将 研究包括ω-3脂肪酸喂养对 脂蛋白脂质代谢及饮食和药物降低血脂的作用 脂蛋白对动脉硬化的影响 这项工作将得到优秀的支持。 脂蛋白测定、载脂蛋白免疫测定和 生物数学分析，并提供了快速进展的承诺， 了解机制并为早产儿提供治疗 与遗传性高脂血症有关的血管疾病。