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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：
8150953
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 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8150953
关键词：
Address Analytical Chemistry Animals Anti-Inflammatory Agents Anti-inflammatory Antioxidants Apolipoproteins A Area Atherosclerosis Award Basic Science Biological Biomedical Research Budgets Cardiovascular Diseases Cell Culture Techniques Cells Cholesterol Collaborations Complex Country Data Development Development Plans Diabetes Mellitus Disease Doctor of Philosophy Environment Equilibrium Faculty Funding Generations Genome Goals Goat Grant High Density Lipoproteins High Pressure Liquid Chromatography Human In Vitro Inflammation Inflammatory Institutes Investigation Journals Knowledge Laboratories Lead Learning Lipids Lipoproteins Medicine Mentors Mentorship Metabolism Modification Molecular Obesity Paper Pathway interactions Peer Review Performance Phase Play Positioning Attribute Postdoctoral Fellow Probability Process Property Protein Chemistry Proteins Proteomics Publishing Relative (related person)Research Research Personnel Research Training Rewards Rodent Model Role Sampling Science Scientist Self Assessment Structure Techniques Testing Time Training United States United States National Institutes of Health Universities Vascular Diseases Washington Work career career development combat diabetic diabetic cardiomyopathy experience human tissue in vivo inhibitor/antagonist instrumentation medical schools member multidisciplinary novel diagnostics novel therapeutic intervention oxidation oxidative damage prevent professor programs research study skills

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）通过清除动脉细胞中多余的胆固醇来防止动脉粥样硬化。HDL也被认为是体内细胞炎症和脂质氧化的重要抑制剂。此外，炎症已被提出将HDL转化为失去这些心脏保护作用的功能障碍形式，甚至可能是促炎性的。两个重要的途径可能涉及氧化损伤和HDL中促氧化蛋白和抗氧化蛋白相对平衡的变化。在该奖项的前两年，PI已经完成了一个高度结构化的职业发展计划，为他过渡到一个完全独立的调查员做好准备。在此期间，他在同行评审期刊上发表了五篇第一作者论文，直接解决了原始提案中提出的假设。重要的是，他已经在糖尿病患者中获得了强有力的初步数据，表明产生功能障碍的HDL的拟议机制与病理生理学相关。PI与华盛顿大学的翻译研究人员合作，为开发一项以了解HDL在糖尿病心血管疾病中的作用为中心的研究计划奠定了基础。重要的是，拟议的研究完全独立于他的导师。他还接受了华盛顿大学的教职，医学系为他分配了独立的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/R 00奖项的下一阶段，PI将专注于两个主要目标：首先，建立一个以糖尿病和心血管疾病为中心的完全独立的研究项目。第二，为他的研究获得NIH的资助。长期目标是通过了解患有糖尿病和其他炎症性疾病的人中功能失调的HDL产生的分子机制来对抗动脉粥样硬化。