Anti-inflammatory properties of high-density lipoprotein

高密度脂蛋白的抗炎特性

• 批准号: 7532353
• 负责人: Baohai Shao
• 金额: $ 9万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7532353
• 关键词: 3-chlorotyrosine; ATP-Binding Cassette Transporters; Academic Medical Centers; Address; Affect; Age; Animal Disease Models; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Apolipoproteins; Apolipoproteins A; Arteries; Atherosclerosis; Award; Basic Science; Biological Models; Biology; Blood Vessels; Blood specimen; Cardiovascular Diseases; Carotid Stenosis; Cell membrane; Cells; Cholesterol; Collaborations; Complement; Computational Biology; Condition; Coronary Arteriosclerosis; Coronary Occlusions; Development Plans; Disease; Endothelial Cells; Enzymes; Equilibrium; Event; Excision; Exhibits; Exposure to; Funding; Goals; Granulocyte-Macrophage Colony-Stimulating Factor; High Density Lipoproteins; Human; Hypochlorous Acid; Hypochlorous Acids; Immune system; Incubated; Inflammation; Inflammatory; Knockout Mice; Lead; Lipids; Lipoproteins; Low Density Lipoprotein Receptor; Mass Spectrum Analysis; Mediating; Membrane Transport Proteins; Mentors; Methionine; Modeling; Molecular; Mus; Mutate; Pathogenesis; Pathway interactions; Patients; Peroxidase; Phenotype; Phospholipids; Plasma; Positioning Attribute; Principal Investigator; Process; Production; Property; Proteins; Proteomics; Race; Reaction; Relative (related person); Research; Research Personnel; Role; Shotguns; Site; Structure; Syndrome; Testing; Therapeutic; Training; Tyrosine; Ultrasonography; atherogenesis; atheroprotective; career; cerebrovascular; chlorination; hypercholesterolemia; in vivo; inhibitor/antagonist; insight; low density lipoprotein inhibitor; macrophage; men; monocyte; mouse model; novel diagnostics; oxidation; oxidized lipid; particle; prevent; programs; protective effect; reverse cholesterol transport; sex; tissue culture; translational study

DESCRIPTION (provided by applicant): It is widely believed that high-density lipoprotein (HDL) protects against atherosclerosis by removing excess cholesterol from arterial cells. In addition to HDL's role in cholesterol transport and removal, increasing evidences support its functions as an important inhibitor of cellular inflammation and lipid oxidation in vivo. Moreover, inflammation has been proposed to convert HDL to a dysfunctional form that loses these cardio protective effects and may even be pro-inflammatory. The underlying factors that render HDL pro-inflammatory remain poorly understood. Two important pathways may involve oxidative damage and changes in the relative balance of pro- and antioxidant proteins in HDL. This proposal outlines a highly structured career development plan that will promote the transition of the applicant to a fully independent investigator. The major component of the proposal is intense exposure to basic science studies that will test the hypothesis that oxidation and changes in the protein cargo impair the anti inflammatory and cardio protective effects of HDL. The applicant will be mentored during the first two years of the award. This period of training will build upon his strong background in mass spectrometry and extend his expertise to model system studies, computational biology, and animal models of hypercholesterolemia. The applicant will also initiate translational studies that will use a proteomics approach to define the protein cargo of HDL. In the last three years of the award, the applicant will develop an independent research program centered on understanding the role of HDL in vascular wall biology, with an emphasis on murine models of inflammation and atherosclerosis. The long term goal is to establish the applicant as a fully independent biomedical investigator in an NIH-funded tenure-track position at an academic medical center.

描述（由申请人提供）： 人们普遍认为，高密度脂蛋白（HDL）通过从动脉细胞中清除多余的胆固醇来防止动脉粥样硬化。除了HDL在胆固醇转运和清除中的作用外，越来越多的证据支持其作为体内细胞炎症和脂质氧化的重要抑制剂的功能。此外，炎症已被提出将HDL转化为功能失调的形式，失去这些心脏保护作用，甚至可能是促炎性的。使HDL促炎的潜在因素仍然知之甚少。两个重要的途径可能涉及氧化损伤和HDL中的亲和抗氧化蛋白的相对平衡的变化。 该建议概述了一个高度结构化的职业发展计划，将促进申请人过渡到一个完全独立的调查员。该提案的主要组成部分是大量接触基础科学研究，这些研究将测试蛋白质货物的氧化和变化会损害HDL的抗炎和心脏保护作用的假设。申请人将在获奖的前两年接受指导。这段时间的培训将建立在他在质谱学的强大背景，并扩展他的专业知识，模型系统研究，计算生物学和高胆固醇血症的动物模型。申请人还将启动翻译研究，该研究将使用蛋白质组学方法来定义HDL的蛋白质货物。在该奖项的最后三年，申请人将开发一个独立的研究计划，重点是了解HDL在血管壁生物学中的作用，重点是炎症和动脉粥样硬化的小鼠模型。 长期目标是使申请人成为一名完全独立的生物医学研究员，在学术医疗中心担任NIH资助的终身职位。