Anti-inflammatory properties of high-density lipoprotein

高密度脂蛋白的抗炎特性

基本信息

批准号：
7663157
负责人：
Baohai Shao
金额：
$ 9万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
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/7663157
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 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 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 Peroxidases 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 development cerebrovascular chlorination hypercholesterolemia in vivo inhibitor/antagonist insight macrophage men monocyte mouse model novel diagnostics oxidation oxidative damage oxidized lipid particle prevent programs protective effect reverse cholesterol transport sex tissue culture translational study

项目摘要

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）通过从动脉细胞中去除多余的胆固醇来预防动脉粥样硬化。除了HDL在胆固醇转运和去除中的作用外，增加的证据还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，已经提出了炎症将HDL转换为失去这些有氧保护作用的功能失调的形式，甚至可能是促炎性的。引起HDL促炎性的基本因素仍然鲜为人知。两种重要的途径可能涉及HDL中促氧化和抗氧化剂蛋白的相对平衡的氧化损伤和变化。该提案概述了一项高度结构化的职业发展计划，该计划将促进申请人向完全独立的研究者的过渡。该提案的主要组成部分是强烈接触基础科学研究，该研究将检验以下假设：氧化和蛋白质货物的变化会损害HDL的抗炎和有氧保护作用。申请人将在奖励的前两年进行指导。这段训练将基于他在质谱学方面的强大背景，并将其专业知识扩展到模型系统研究，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中，申请人将制定一项独立的研究计划，该计划以了解HDL在血管壁生物学中的作用为中心，重点是炎症和动脉粥样硬化的鼠模型。长期目标是将申请人建立为完全独立的生物医学研究员，并在NIH资助的终身医学中心担任终身制职位。