CLINICAL STUDIES IN NUTRITION AND METABOLISM

营养和代谢的临床研究

• 批准号: 6783274
• 负责人: Ishwarlal Jialal
• 金额: $ 11.78万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6783274
• 关键词: alternative medicine; antihypercholesterolemic agent; antioxidants; atherosclerosis; blood lipoprotein metabolism; cell adhesion molecules; clinical research; dietary lipid; dietary supplements; disease /disorder proneness /risk; flavonoids; human subject; inflammation; leukocyte activation /transformation; lipoxygenase; low density lipoprotein; nuclear factor kappa beta; nutrition related tag; oxidative stress; plant extracts; postgraduate education; protein kinase C; racial /ethnic difference; tocopherols; unsaturated fatty acids

Cardiovascular disease is the leading cause of morbidity and mortality in the United States. Current evidence suggests that both inflammation and oxidative stress are crucial in atherogenesis and that dietary antioxidants may be beneficial. Since 1988 the candidate's group has made significant observations in the area, especially as it relates to patient oriented research. In this proposal, which is a logical extension, the following studies will be undertaken: 1) The effect of high dose alpha-tocopherol (AT) supplementation on LDL oxidation, monocyte pro-atherogenic activity and carotid atherosclerosis in patients with coronary artery disease; 2) The effect of pycnogenol alone and in combination with AT on measures of oxidative stress; 3) Interaction between N-3 PUFA and AT on inflammation and LDL oxidation; 4) The effect of HMG-CoA reductase inhibitors on plasma levels of remnant lipoproteins; 5) Evolving cardiovascular risk factors in African Americans and Caucasians; and 6) A dose response study on the effect of AT on inflammation. The measures of oxidative stress include plasma oxidation by assaying protein carbonyls, LDL oxidative susceptibility and the quantitation of urinary F2.isoprostanes. Inflammatory markers that will be studied include. plasma levels of soluble adhesion molecules s-ICAM, s-VCAM, sE-selectin and sP-selectin and C-reactive protein. The functions that will be assayed in activated monocytes are superoxide anion, IL-1beta, TNF-alpha, tissue factor, and monocyte endothelial adhesion. In Project V, in addition to studying measures of oxidative stress and inflammation, we will determine the role of homocysteine and Chlamydia pneumoniae in predicting atherosclerosis by EBCT. In Project VI mechanistic insights will be gained by studying PKC, 5-LO and NFkappa-b activity. These studies coupled with didactic courses and clinical exposure at UT Southwestern provide an excellent training ground for mentorees in patient oriented research. The studies outlined in this proposal clearly enhance the long-term objectives of the PI, since his major interest is in the role of nutritional factors on lipoproteins and critical cells in atherogenesis. These studies in aggregate will definitely contribute to our understanding of atherosclerosis.

心血管疾病是美国发病率和死亡率的主要原因。 目前的证据表明，炎症和氧化应激在动脉粥样硬化形成中都至关重要，饮食中的抗氧化剂可能是有益的。自 1988 年以来，该候选人的团队在该领域做出了重大观察，特别是在以患者为导向的研究方面。在这一逻辑延伸的提案中，将进行以下研究： 1）补充高剂量α-生育酚（AT）对冠状动脉疾病患者的 LDL 氧化、单核细胞促动脉粥样硬化活性和颈动脉粥样硬化的影响； 2) 碧容健单独使用以及与 AT 联合使用对氧化应激指标的影响； 3) N-3 PUFA 和 AT 对炎症和 LDL 氧化的相互作用； 4) HMG-CoA还原酶抑制剂对血浆残余脂蛋白水平的影响； 5) 非裔美国人和白种人不断变化的心血管危险因素； 6) AT 对炎症影响的剂量反应研究。氧化应激的测量包括通过测定蛋白质羰基来测定血浆氧化、LDL氧化敏感性和尿F2.异前列腺素的定量。 将研究的炎症标志物包括。可溶性粘附分子 s-ICAM、s-VCAM、sE-选择素和 sP-选择素以及 C 反应蛋白的血浆水平。将在活化的单核细胞中检测的功能是超氧阴离子、IL-1β、TNF-α、组织因子和单核细胞内皮粘附。在项目 V 中，除了研究氧化应激和炎症的测量之外，我们还将通过 EBCT 确定同型半胱氨酸和肺炎衣原体在预测动脉粥样硬化中的作用。在项目 VI 中，将通过研究 PKC、5-LO 和 NFkappa-b 活动来获得机制见解。 这些研究与德克萨斯大学西南医学中心的教学课程和临床接触相结合，为以患者为导向的研究的导师提供了极好的训练场地。该提案中概述的研究明显增强了 PI 的长期目标，因为他的主要兴趣是营养因素对脂蛋白和动脉粥样硬化形成中关键细胞的作用。这些研究总的来说肯定有助于我们对动脉粥样硬化的理解。