ADRENAL HORMONES AND ATHEROSCLEROSIS

肾上腺激素和动脉粥样硬化

• 批准号: 3345326
• 负责人: DON H NELSON
• 金额: $ 10.6万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1987-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3345326
• 关键词: adrenal glands; adrenocorticotropic hormone; angiography; atherosclerosis; coronary disorder; corticosteroids; human subject; lymphocyte; membrane lipids; monocyte; neutrophil; phosphatidylcholines; sphingomyelins; thin layer chromatography

The long-term objectives of this research project are to understand the relation of the adrenal cortex to the production of coronary artery disease and to determine whether changes in the phospholipid content of leukocyte membranes found to occur in patients with coronary artery disease (CAD) are the result of increased adrenal secretion. An increase in the phosphatidylcholine to sphingomyelin ratio (PC/Sph) has been found in membranes isolated from human polymorphonuclear leukocytes obtained from patients receiving corticosteroids, patients with Cushing's syndrome, and patients who have proven coronary artery disease. Studies are to be carried out in a larger group of patients to confirm the observed changes in PC/Sph in patients with CAD and determine if these lipid changes occur in lymphocytes and monocytes. Polymorphonuclear leukocytes are isolated from 20 ml blood samples drawn at 8 a.m. from fasting subjects. Viability of the cells is assured by using only those which attach to glass Petri dishes following the initial isolation on Ficoll-Hypaque. These cells are scraped from the plates, lipids are extracted by the procedure of Bligh and Dyer, applied to silica coated chromarods, separated by thin layer chromatography, and quantified by flame ionization in a latroscan. Patients used in this study initially will be those undergoing coronary angiography to determine the presence of coronary artery disease. Those found to have greater than 70% occlusion of one or more arteries are considered to have CAD while those with less than 25% occlusion make up the control group. Determination of adrenal secretion and responsivity to ACTH in a control group and a group of patients with proven CAD will also be performed. Previous studies have demonstrated increased responsivity of the adrenal gland and higher than normal ACTH levels in patients with CAD. Estimation of leukocyte membrane PC/Sph and adrenal studies will be carried out to determine if there is a correlation between these two findings in patients with CAD. In addition, plasma corticoids will be increased by administration of cortisol or ACTH for a few hours each day to determine whether this is sufficient to produce the changes in membrane lipids noted in patients receiving more prolonged corticoids or in those with proven CAD. If this is found to be true, it will be consistent with patients who are found to have therapeutic effects from corticosteroids given intermittently as in alternate day therapy.

本研究项目的长期目标是了解 肾上腺皮质与冠状动脉疾病发生的关系 并确定白细胞磷脂含量的变化是否 冠状动脉疾病（CAD）患者中发现的膜是 肾上腺分泌增加的结果。 的增加 磷脂酰胆碱与鞘磷脂的比例（PC/Sph）已被发现， 分离自人多形核白细胞的膜， 接受皮质类固醇的患者，患有库欣综合征的患者，以及 已确诊冠心病的患者。 研究将是 在更大的患者组中进行，以确认观察到的变化 在CAD患者的PC/Sph中，并确定这些脂质变化是否发生 在淋巴细胞和单核细胞中。 分离多态性白细胞 从空腹受试者在上午8点抽取的20 ml血液样品中。 活力 通过只使用那些附着在玻璃培养皿上的细胞， 在Ficoll-Hypaque上初始分离后的培养皿中。 这些细胞 从平板上刮下，通过Bligh的方法提取脂质， 染料，适用于涂有二氧化硅的镀铬棒，由薄层隔开 通过柱色谱法纯化，并在latroscan中通过火焰离子化定量。 本研究最初使用的患者将接受冠状动脉造影术 冠状动脉造影以确定冠状动脉疾病的存在。 那些 发现一个或多个动脉闭塞超过70%的患者， 被认为患有CAD，而小于25%闭塞的患者构成了 对照组 肾上腺分泌和对ACTH反应性的测定 在对照组和一组确诊CAD的患者中， 执行。 以前的研究表明， CAD患者肾上腺皮质和ACTH水平高于正常人。 进行白细胞膜PC/Sph和肾上腺研究 为了确定这两个发现之间是否存在相关性， CAD患者 此外，血浆皮质激素将增加， 每天给予皮质醇或ACTH几个小时，以确定 这是否足以引起膜脂的变化 在接受更长时间皮质激素治疗的患者中， CAD. 如果这是真的，这将是一致的病人， 被发现有治疗效果，从皮质类固醇给予 像隔日治疗一样间歇性地进行。