DYSLIPOPROTEINEMIA IN SILENT MYOCARDIAL ISCHEMIA

在获得生物物理学博士学位期间准备的基础科学培训 生物医学研究领域的候选人。临床培训 老年病学补充了这一基础，产生了一位感兴趣的科学家 在应用基本生化技术研究衰老对人的影响方面 冠心病(CAD)的代谢危险因素。研究作为一种 研究员认为，20个衰老过程(疾病、缺乏运动和 饮食)和遗传因素比衰老本身更重要 计算机辅助设计的发展。在一组没有明显风险的老年男性中 冠心病的因素，无症状性心肌缺血(SI)被归因于“老年” 年龄“；然而，候选人在High中发现了微妙的异常 密度脂蛋白(HDL)代谢。这表明衰老本身就是 并不是导致这些男性动脉粥样硬化的唯一原因。接受这一奖项 将申请者的研究培训扩展到对 老年人血脂异常的病理生理及分子遗传学研究 患有SI的男性。专门的研究时间将允许应聘者发展 临床、生物医学研究和分子方面的附加技能 成为一名独立的临床研究员所需的生物学 老龄化研究。这些技能将在丰富的研究中传授 约翰霍普金斯大学、美国国家老龄研究所、美国国立卫生研究院和 大学。这项研究的主要假设是 否则，患有SI的健康老年男性既有遗传上的和/或后天的 肝酶对高密度脂蛋白代谢调节的异常 脂肪酶和脂蛋白脂肪酶可降低HDL6和载脂蛋白A-I水平 增加餐后血脂和低密度脂蛋白的载脂蛋白B含量。这一假设 将通过以下方面进行测试：(1)对患有SL和IN的老年男性的代谢研究 匹配的正常对照组，以检测高密度脂蛋白代谢的调节 空腹和餐后状态；(2)检测大鼠的代谢反应 SI患者以低脂肪/低胆固醇饮食或减肥；以及(3) 家族性研究评估遗传性脂蛋白异常的存在 一些患有SI的人。高密度脂蛋白与富含甘油三酯的关系分析 脂蛋白和调节酶可能阐明相关的机制 对于异常的高密度脂蛋白代谢。家庭研究将确定是否存在 一种遗传性脂蛋白异常症，并可能提高患者在 对CAD来说风险很高。对血脂异常发病机制的认识 在男性SI中，对营养干预的反应可能提供 对可能延缓或逆转 CAD的进展。

Basic science training during a receipt of a Ph.D. in biophysics prepared the candidate for a career in biomedical research. Clinical training in geriatrics complemented this foundation, producing a scientist interested in applying basic biochemical skills to study the effects of aging on metabolic risk factors for coronary artery disease (CAD). Research as a fellow suggested that 20 aging processes (disease, physical inactivity and diet) and genetic factors were more important than aging itself in the development of CAD. In a subgroup of older men without apparent risk factors for CAD, silent myocardial ischemia (SI) was attributed to "old age"; however, the candidate discovered subtle abnormalities in high density lipoprotein (HDL) metabolism. This suggested that aging itself was not the only cause of atherosclerosis in these men. Receipt of this award will extend the research training of the applicant to the investigation of the pathophysiology and molecular genetics of dyslipoproteinemia in older men with SI. Dedicated research time will permit the candidate to develop the additional skills in clinical and biomedical research and molecular biology necessary for independent stature as a clinical investigator in aging research. These skills will be taught in the enriched research environment at Johns Hopkins, the National Institutes of Aging, NIH and the Univ. of California.The major hypothesis of this research is that other-wise healthy older men with SI have both genetic and/or acquired abnormalities in the regulation of HDL metabolism by the enzymes hepatic lipase and lipoprotein lipase that reduce HDL6 and Apo A-I levels and increase postprandial lipemia and Apo B enrichment of LDL. This hypothesis will be tested by: (1) Metabolic studies in older men with Sl and in matched normal controls to examine the regulation of HDL metabolism in the fasted and postprandial state; (2) Examining the metabolic responses of patients with SI to low fat/low cholesterol diets or weight loss; and (3) Family studies to evaluate the presence of a genetic dyslipoproteinemia in some men with SI. Analysis of the relationship of HDL to TG-rich lipoprotein and regulatory enzymes may elucidate the mechanisms responsible for the abnormal HDL metabolism. Family studies will determine the presence of a genetic dyslipoproteinemia and may improve the detection of patient at high risk for CAD. Knowledge of the pathogenesis of the lipid abnormalities in men with SI and the responses to nutritional interventions may provide insights into interventions which could potentially retard or reverse the progression of CAD.