CLINICAL STUDIES IN NUTRITION AND METABOLISM

营养和代谢的临床研究

• 批准号: 6660340
• 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/6660340
• 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中都是至关重要的，饮食中的抗氧化剂可能是有益的。自1988年以来，候选人的小组对该地区进行了重大观察，尤其是与患者的研究有关。在这项逻辑扩展的建议中，将进行以下研究：1）补充高剂量α-生育酚（AT）对LDL氧化，单核细胞促动脉粥样硬化活性和颈动脉粥样硬化对冠状动脉疾病患者的影响； 2）单独和与AT的氧化应激测量值结合的效果； 3）N-3 PUFA与炎症和LDL氧化之间的相互作用； 4）HMG-COA还原酶抑制剂对残留脂蛋白水平水平的影响； 5）非洲裔美国人和高加索人的心血管危险因素不断发展； 6）对AT炎症作用的剂量反应研究。氧化应激的度量包括通过测定蛋白羰基，LDL氧化敏感性和尿液F2.异前坦的定量来进行血浆氧化。 将研究的炎症标记包括。可溶性粘附分子S-ICAM，S-VCAM，SE-选择蛋白和SP-选择蛋白以及C反应蛋白的血浆水平。将在活化的单核细胞中测定的功能是超氧化阴离子，IL-1Beta，TNF-Alpha，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措施外，我们还将确定同型半胱氨酸和衣原体肺炎在EBCT预测动脉粥样硬化中的作用。在VI项目中，将通过研究PKC，5-LO和NFKAPPA-B活性来获得洞察力。 这些研究结合了UT西南部的教学课程和临床暴露，为以患者为导向的研究提供了良好的训练场。该提案中概述的研究显然增强了PI的长期目标，因为他的主要兴趣是营养因素对脂蛋白和关键细胞在动脉粥样硬化中的作用。这些总体研究肯定会有助于我们对动脉粥样硬化的理解。