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：
8293138
负责人：
Baohai Shao
金额：
$ 24.9万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-08-20 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8293138
关键词：
3-chlorotyrosine ATP-Binding Cassette Transporters Address Affect Age Animal Disease Models Animal Model Animals Anti-Inflammatory Agents Anti-inflammatory Antioxidants Apolipoproteins Apolipoproteins A Arteries Atherosclerosis Award Biology Blood specimen Cardiovascular Diseases Carotid Stenosis Cell membrane Cells Cholesterol Collaborations Complement Coronary Arteriosclerosis Coronary Occlusions Data Development Plans Diabetes Mellitus Disease Endothelial Cells Enzymes Equilibrium Event Exhibits Faculty Funding Generations Goals Granulocyte-Macrophage Colony-Stimulating Factor High Density Lipoproteins Human Hypochlorous Acid Immune system Incubated Inflammation Inflammatory Instruction Journals Knockout Mice Laboratories Lead Lipids Lipoproteins Low Density Lipoprotein Receptor Mediating Medicine Membrane Transport Proteins Mentors Methionine Molecular Mus Mutate Obesity Paper Pathogenesis Pathway interactions Patients Peer Review Peroxidases Phase Phenotype Phospholipids Plasma Positioning Attribute Principal Investigator Process Production Property Proteins Proteomics Publishing Race Reaction Relative (related person)Research Research Personnel Role Shotguns Site Structure Syndrome Testing Time Tyrosine Ultrasonography United States National Institutes of Health Universities Washington atherogenesis atheroprotective career development cerebrovascular chlorination combat diabetic diabetic cardiomyopathy hypercholesterolemia in vivo inhibitor/antagonist insight macrophage men monocyte mouse model novel diagnostics novel therapeutic intervention oxidation oxidative damage oxidized lipid particle prevent programs research study reverse cholesterol transport sex tissue culture

项目摘要

High-density lipoprotein (HDL) protects against atherosclerosis by removing excess cholesterol from arterial cells. HDL has also been proposed to function 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 cardioprotective effects and may even be pro-inflammatory. Two important pathways may Involve oxidative damage and changes in the relative balance of pro- and antioxidant proteins in HDL. During the first two years of the award, the PI has completed a highly structured career development plan to prepare him for transition to a fully independent investigator. During this time, he has published five first author papers in peer-reviewed journals, that have directly addressed the hypotheses raised in the original proposal. Importantly, he has obtained strong preliminary data in diabetic humans that the proposed mechanisms for generation of dysfunctional HDL are pathophysiologically relevant. In collaboration with translational investigators at the University of Washington, the PI has laid the groundwork for developing a research program centered on understanding the role of HDL in diabetic cardiovascular disease. Importantly, the proposed studies are completely Independent of that of his mentor. He also has accepted a faculty position with the University of Washington and the Department of Medicine has assigned him independent laboratory space and an office at the newly established Diabetes and Obesity Center of Excellence. During the next phase of the K99/R00 award, the PI will focus on two major goals: first, establishing a fully independent research program centered on diabetes and cardiovascular diseases. Second, obtaining NIH funding for his research studies. The long-term goal is to combat atherosclerosis by understanding the molecular mechanisms for generation of dysfunctional HDL in humans suffering from diabetes and other inflammatory conditions.

高密度脂蛋白（HDL）通过从动脉中去除多余的胆固醇来预防动脉粥样硬化细胞。还建议HDL充当细胞炎症和脂质的重要抑制剂体内氧化。此外，已经提出炎症将HDL转换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。两个重要的途径可能涉及氧化损伤以及HDL中促氧化剂蛋白和抗氧化剂蛋白的相对平衡的变化。在奖项的前两年中，PI完成了一项高度结构化的职业发展计划他准备过渡到完全独立的调查员。在此期间，他首先出版了五个在同行评审期刊上的作者论文，这些论文直接解决了原始的假设提议。重要的是，他在糖尿病人类中获得了强大的初步数据产生功能失调的HDL的机制在病理生理上是相关的。与华盛顿大学的翻译调查员，PI为开发一个研究计划的重点是了解HDL在糖尿病心血管疾病中的作用。重要的是，拟议的研究完全独立于他的导师。他还接受了教师华盛顿大学和医学系任命他独立实验室空间和新成立的糖尿病和肥胖卓越中心的办公室。在K99/R00奖的下一阶段，PI将重点关注两个主要目标：首先，建立一个完全独立研究计划以糖尿病和心血管疾病为中心。第二，获得NIH 为他的研究提供资金。长期目标是通过了解患有糖尿病和其他人的人类生成功能失调的HDL的分子机制炎症条件。