Advanced Glycation Endproducts and Cardio-Renal Disease

晚期糖基化终产物与心肾疾病

基本信息

批准号：
10000127
负责人：
JORGE R KIZER
金额：
$ 12.12万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-15 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10000127
关键词：
Address Advanced Glycosylation End Products Adverse effects Aging Animal Experiments Animal Model Area Blood Vessels Cardiovascular Diseases Cardiovascular system Cell Culture Techniques Cell model Chemosensitization Chronic Chronic Kidney Failure Clinical Clinical Research Communicable Diseases Complications of Diabetes Mellitus Data Defense Mechanisms Development Diabetes Mellitus Discipline Disease Disease Outcome Disease Progression Echocardiography Elderly Endothelial Cells Enzymes Epigenetic Process European Event Exposure to Fibrosis Fostering Future General Population Genes Genetic Genomics Glucose Glyoxal Goals Gold Growth HIV HIV Infections Heart Diseases High Prevalence Homeostasis Hot Spot Human Immunoassay Impairment Individual Investigation Kidney Kidney Diseases Knowledge Lactoylglutathione Lyase Lead Left Left Ventricular Dysfunction Life Link Liquid Chromatography Longevity Magnetic Resonance Imaging Measurement Measures Mechanics Mentors Mentorship Methods Molecular Multi-Ethnic Study of Atherosclerosis Myocardial Myocardial dysfunction N(6)-carboxymethyllysine Nucleic Acids Organism Outcome Oxidative Stress Pilot Projects Plasma Population Post-Translational Protein Processing Prevalence Production Proteins Proteome Public Health Pyruvaldehyde Research Research Infrastructure Research Personnel Research Project Grants Risk Risk Assessment Risk Factors Role Science Specificity Standardization Stroke Testing Training Ventricular Woman Women’s Interagency HIV Study Work adduct adverse outcome base carbohydrate metabolism cardiovascular disorder risk clinically significant cohort coronary fibrosis diabetic epidemiology study epigenomics experimental study falls genome sequencing genome wide association study glomerular filtration glycation healthspan heart imaging high risk population improved interest interstitial knock-down macrovascular disease mesangial cell metabolomics middle age novel therapeutics patient oriented research precision medicine prevent programs prospective protein function renal damage skills sugar tandem mass spectrometry transcriptomics whole genome

项目摘要

PROJECT SUMMARY/ABSTRACT The current application proposes to advance the candidate's program in patient-oriented research through formal training in omics science and mentorship, through an increased level of mentoring of young investigators, and through a research project that will build on the candidate's previous work and afford opportunities to develop his omics research portolio. The research project aims to close knowledge gaps regarding the significance of key advanced glycation endproducts (AGEs) to cardiovascular and renal disease in the general population. To this end, it will undertake gold-standard measurement of a panel comprising the major plasma AGEs, and particularly the quantitatively and functionally most important adducts, methylglyoxal hydroimidazolone (MG-H1) and 3-deoxyglucosone-hydroimidazolones (3DG-H), which have scarcely been evaluated in general clinical or population settings to date. For Aim 1, the project will leverage an ongoing study applying state-of-the-art echocardiography and magnetic resonance imaging (MRI) in women with, or at risk for HIV infection, in the Women's Interagency HIV Study (WIHS) to evaluate the relation of plasma AGEs to abnormal myocardial mechanics and fibrosis in this high-risk population. For Aims 2 and 3, the project will parlay the availability of serial measures of glomerular filtration and standardized ascertainment of cardiovascular events among middle-aged to older adults from the Multi-Ethnic Study of Atherosclerosis (MESA) to investigate the associations of plasma AGEs with progression of chronic kidney disease and incident cardiovascular disease. These studies will provide trainees with a range of exposures to clinical and epidemiologic research to allow their development as investigators. Further, availability genetic/genomic, epigenomic, transcriptomic and metabolomic data in MESA will permit exploration of the omic correlates of AGE levels, setting the stage for larger-scale investigations in the future. Hence, the combination of formal coursework, increased mentorship, and the leveraging of existing research infrastructure to address research questions of major clinical importance will provide the candidate with increased capabilities for POR in precision medicine, and afford opportunities for the growth of his mentees as researchers in this and other disciplines.

项目概要/摘要当前的申请建议推进候选人以患者为中心的计划通过组学科学和指导的正式培训进行研究，通过提高指导年轻的研究人员，并通过一个研究项目，该项目将建立在候选人之前的工作，并提供机会发展他的组学研究组合。这研究项目旨在缩小有关关键先进技术重要性的知识差距糖基化终产物（AGE）对普通人群的心血管和肾脏疾病的影响。到为此，它将对包含主要等离子体的面板进行黄金标准测量 AGE，特别是数量和功能上最重要的加合物，甲基乙二醛氢咪唑酮 (MG-H1) 和 3-脱氧葡萄糖醛酮-氢咪唑酮 (3DG-H)，迄今为止，几乎没有在一般临床或人群环境中进行评估。对于目标 1，该项目将利用一项正在进行的研究，应用最先进的超声心动图和磁力对患有艾滋病毒或有感染艾滋病毒风险的女性进行核磁共振成像 (MRI) 跨机构 HIV 研究 (WIHS) 评估血浆 AGE 与异常心肌的关系这个高危人群的力学和纤维化。对于目标 2 和 3，该项目将充分利用肾小球滤过的系列测量和标准化确定的可用性来自多种族研究的中老年人心血管事件动脉粥样硬化 (MESA) 研究血浆 AGE 与动脉粥样硬化进展的关系慢性肾脏疾病和心血管疾病。这些研究将为学员提供接触一系列临床和流行病学研究，使他们能够发展为调查人员。此外，遗传/基因组、表观基因组、转录组和代谢组学的可用性 MESA 中的数据将允许探索 AGE 水平的组学相关性，为未来将进行更大规模的调查。因此，结合正式课程，加强指导，并利用现有的研究基础设施来解决研究问题具有重大临床重要性的问题将为候选人提供增强的能力 POR在精准医学领域，并为他的学员提供成长机会该学科和其他学科的研究人员。