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: 8467041
• 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/8467041
• 关键词: Acute; Address; Age; Anti-Inflammatory Agents; Anti-inflammatory; Antibodies; Apolipoprotein E; Arizona; Atherosclerosis; Award; Biological Markers; Biometry; Blood; Blood Clot; 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 HDL 蛋白质组的影响 候选人：侯赛因·亚辛 (Hussein Yassine) 在凯斯西储大学完成了住院医师实习，并在施瓦茨代谢中心接受了约翰·科万 (John Kirwan) 博士的运动生理学研究培训。随后，他加入了亚利桑那大学的内分泌学项目，并在 Serrine Lau 博士的指导下接受了蛋白质组学研究的培训。 Yassine 博士对转化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：Yassine 博士的职业目标是成为一名杰出的医师科学家。该目标是通过推进心血管研究、为科学社会做出贡献以及提供卓越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。 Serrine Lau 博士是世界著名的毒理学家，也是亚利桑那州蛋白质组学联盟的主任，对利用最先进的蛋白质组学技术发现生物标志物有着浓厚的兴趣。导师团队和教师角色：Serrine Lau 博士是申请人的主要导师，将负责在获奖阶段推动申请人的职业生涯。刘博士培养了一大批当前活跃、独立、成功的科学家。博士。 George Tsaprailis 和 Linda Breci（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 Craig Stump 博士和脂质紊乱专家 Stanley Goldberg 博士将提供临床研究指导，并确保 Yassine 博士拥有发展成为独立医师科学家的资源。 Dean Billheimer 博士是生物标志物发现领域的生物统计学专家，致力于通过正式会议、讲习班和研讨会来发展 Yassine 博士的生物统计学背景。申请人将就临床队列设计、炎症和心血管疾病向 Peter Reaven 博士咨询。由成功资助的科学家（Price、Funk、Vercelli 博士）组成的顾问团队成立，以评估研究进展并过渡到独立。项目描述：HDL（即好胆固醇）被认为是预测死亡、心脏病和中风的最重要的血液指标之一。 HDL 如何预防动脉粥样硬化和心血管疾病的机制尚不清楚。 HDL 由脂质核心和多种参与炎症和血凝块形成的附着蛋白组成。饮食中的饱和脂肪摄入会增加心血管疾病的风险，并适度增加高密度脂蛋白胆固醇浓度，但其对高密度脂蛋白附着蛋白的影响尚不清楚。我们假设患有糖尿病和心血管疾病的受试者具有富含炎症和促血栓蛋白的高密度脂蛋白，并且饱和脂肪饮食会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。我们的首要目标是利用蛋白质组学技术来鉴定患有或不患有糖尿病和心血管疾病的受试者的 HDL 蛋白质组表型。我们的第二个目标是确定摄入一杯浓奶油后 HDL 蛋白含量的变化。这一发现可以帮助我们了解与心血管疾病有关的高密度脂蛋白的组成变化，并作为开发旨在减轻心血管疾病负担的新疗法的标志物。