The Effect of Saturated Fat Ingestion on the HDL Proteome

饱和脂肪摄入对 HDL 蛋白质组的影响

• 批准号: 8661251
• 负责人: Hussein N Yassine
• 金额: $ 12.25万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8661251
• 关键词: Acute; Address; Age; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Apolipoprotein E; Arizona; Atherosclerosis; Award; Biological Markers; Biometry; Blood; Blood coagulation; Cardiovascular Diseases; Cardiovascular system; Cessation of life; Cholesterol; Clinical; Clinical Research; Commit; Complement; Consult; Cream; Data; Development; Diabetes Mellitus; Diet; Dyslipidemias; Early identification; Educational workshop; Endocrinology; Ensure; Environment; Epidemiology; Exercise Physiology; Faculty; Fatty acid glycerol esters; Funding; Glycoproteins; Goals; Hand; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Hour; Individual; Inflammation; Inflammatory; Ingestion; Institution; Intake; Ions; Laboratories; Lipids; Mass Spectrum Analysis; Measures; Mentors; Mentorship; Metabolism; Methods; Myocardial Infarction; Nature; Non-Insulin-Dependent Diabetes Mellitus; Oxidative Stress; Paraoxonase 1; Patient Care; Phase; Phenotype; Physicians; Plasma; Price; Proteins; Proteome; Proteomics; Recruitment Activity; Research; Research Personnel; Research Proposals; Research Training; Residencies; Resources; Role; Sampling; Scientific Societies; Scientist; Stroke; Supervision; Techniques; Technology; Testing; Training; Translating; Translational Research; Universities; Vascular Endothelium; apolipoprotein A-IV; apolipoprotein D; base; burden of illness; cardiovascular disorder risk; career; clinical practice; cohort; design; feeding; interest; lipid disorder; meetings; multiple reaction monitoring; non-diabetic; novel; particle; patient oriented research; professor; programs; research facility; saturated fat; success; sulfated glycoprotein 2

DESCRIPTION (provided by applicant): The Effect of Saturated Fat Ingestion on the HDL Proteome The candidate: Hussein Yassine completed his residency at Case Western Reserve University with additional research training in exercise physiology at Schwartz Center of Metabolism by Dr. John Kirwan. He then joined the endocrinology program at the University of Arizona and trained in proteomics research under the supervision of Dr. Serrine Lau. Dr. Yassine has a strong interest in translational research. He is currently an Assistant Professor at the University of Arizona. Career Goals: Dr. Yassine's career goal is to be an outstanding physician-scientist. The goal is achieved by advancing cardiovascular research, contributing to the scientific society and providing excellent patient care. Institution: The University of Arizona has a state-of-the-art proteomics consortium and laboratory. Dr. Serrine Lau is a world renowned toxicologist and the director of the Arizona Proteomics Consortium with a strong interest in biomarker discovery using state-of-the art proteomic technology. Mentoring Team and Faculty Roles: Dr. Serrine Lau is the applicant's primary mentor, and will be responsible for advancing the applicant's career during the award phase. Dr. Lau has trained a large number of currently active, independent and successful scientists. Drs. George Tsaprailis and Linda Breci (proteomics core) will provide training in proteomics through courses, and hands on workshops. Dr. Craig Stump, Chief of Endocrinology and an expert in oxidative stress, and Dr. Stanley Goldberg, an expert in lipid disorders, will provide mentorship in clinical research, and will ensure that Dr. Yassine will have the resources to develop into an independent physician-scientist. Dr. Dean Billheimer, an expert in biostatistics for biomarker discovery, is committed to developing Dr. Yassine's biostatistics background through formal meetings, workshops and seminars. The applicant will consult with Dr. Peter Reaven on clinical cohort design, inflammation and cardiovascular disease. An advisory team of successfully funded scientists (Drs. Price, Funk, Vercelli) is formed to assess research progress and transitioning into independence. Project description: HDL, or good cholesterol, is considered one of the most important blood measures in predicting death, heart attacks and strokes. The mechanism of how HDL protects against atherosclerosis and cardiovascular disease is poorly understood. HDL consists of a lipid core and a wide array of attached proteins involved in inflammation and blood clot formation. Saturated fat intake in the diet increases the risk of cardiovascular disease with modest increases in HDL cholesterol concentrations, but its effect on HDL attached proteins is not known. We hypothesize that subjects with diabetes and cardiovascular disease have HDL enriched with inflammatory and prothrombotic proteins, and that a saturated fatty diet generates an HDL particle enriched in inflammatory proteins. The University of Arizona possesses a world- renowned proteomics research facility that discovers proteins at very low concentrations. Our first aim is to employ proteomic technologies to identify HDL proteome phenotypes in subjects with and without diabetes and cardiovascular disease. Our second aim is to identify the changes of the HDL protein cargo after ingesting a cup of heavy whipped cream. This discovery could help us understand the composition changes of HDL involved in cardiovascular disease, and serve as a marker to develop novel therapies aimed at decreasing the cardiovascular disease burden.

描述(由申请人提供)：饱和脂肪摄入对高密度脂蛋白蛋白质组的影响候选人：侯赛因·亚辛完成了他在凯斯西储大学的住院医师生涯，并在施瓦茨新陈代谢中心接受了由John Kirwan博士进行的额外运动生理学研究培训。然后，他加入了亚利桑那大学的内分泌学项目，并在刘思林博士的指导下接受了蛋白质组学研究方面的培训。亚辛博士对翻译研究有着浓厚的兴趣。他目前是亚利桑那大学的助理教授。职业目标：亚辛博士的职业目标是成为一名杰出的内科科学家。这一目标是通过推进心血管研究、为科学社会做出贡献并提供优质的患者护理来实现的。机构：亚利桑那大学拥有最先进的蛋白质组学联盟和实验室。刘思林博士是世界著名的毒物学家，也是亚利桑那州蛋白质组学联盟的负责人，他对使用最先进的蛋白质组技术发现生物标记物有着浓厚的兴趣。指导团队和教师角色：刘思林博士是申请者的主要导师，并将负责在颁奖阶段推进申请者的职业生涯。刘博士培养了一大批目前活跃、独立、成功的科学家。乔治·特萨雷里斯博士和琳达·布雷奇博士(蛋白质组学核心)将通过课程和实践研讨会提供蛋白质组学培训。内分泌科主任、氧化应激专家克雷格·斯坦普博士和脂质紊乱专家斯坦利·戈德堡博士将为临床研究提供指导，并将确保亚辛博士拥有发展成为独立内科科学家的资源。迪恩·比尔海默博士是生物标志物发现方面的生物统计学专家，他致力于通过正式会议、研讨会和研讨会发展亚辛博士的生物统计学背景。申请者将就临床队列设计、炎症和心血管疾病咨询Peter Reaven博士。成立了一个由成功资助的科学家(普莱斯、芬克、韦尔塞利博士)组成的顾问团队，以评估研究进展和向独立过渡。项目描述：高密度脂蛋白，或好胆固醇，被认为是预测死亡、心脏病发作和中风的最重要的血液指标之一。高密度脂蛋白如何预防动脉粥样硬化和心血管疾病的机制还知之甚少。高密度脂蛋白由一个脂质核心和一系列参与炎症和血液凝块形成的附着蛋白组成。饮食中饱和脂肪的摄入会增加心血管疾病的风险，并适度增加高密度脂蛋白的浓度，但其对高密度脂蛋白结合蛋白的影响尚不清楚。我们假设糖尿病和心血管疾病患者的高密度脂蛋白富含炎症和血栓前蛋白，饱和脂肪饮食产生富含炎症蛋白的高密度脂蛋白颗粒。亚利桑那大学拥有世界著名的蛋白质组学研究设施，可以发现极低浓度的蛋白质。我们的第一个目标是利用蛋白质组学技术来鉴定患有和不患有糖尿病和心血管疾病的受试者的高密度脂蛋白蛋白质组表型。我们的第二个目标是确定摄入一杯重搅打奶油后高密度脂蛋白含量的变化。这一发现可以帮助我们了解高密度脂蛋白在心血管疾病中的组成变化，并作为开发旨在减轻心血管疾病负担的新疗法的标志。