Advanced Glycation Endproducts and Cardio-Renal Disease

晚期糖基化终产物与心肾疾病

• 批准号: 9386273
• 负责人: JORGE R KIZER
• 金额: $ 12.12万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 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/9386273
• 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; cardiovascular visualization; clinically significant; cohort; coronary fibrosis; diabetic; disorder risk; epidemiology study; epigenomics; experimental study; falls; genome sequencing; genome wide association study; glomerular filtration; glycation; 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; skills; sugar; tandem mass spectrometry; transcriptomics; whole genome

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.

项目摘要/摘要 当前的申请建议以患者为导向的候选人计划 通过对OMICS科学和指导的正式培训进行的研究，通过增加 指导年轻的调查人员，并通过一个将基于的研究项目 候选人以前的工作和提供了开发其OMICS研究Portolio的机会。这 研究项目旨在弥合有关关键高级意义的知识差距 普通人群的糖基化最终产物（年龄）。到 这一末端，它将对包括主要等离子体的面板进行金标准测量 年龄，尤其是定量和功能上最重要的加合物，甲基甘氨酸 羟基咪唑酮（MG-H1）和3-脱氧葡萄糖苷 - 羟基二唑唑酮（3DG-H），其具有 迄今为止，几乎没有在一般临床或人口环境中评估。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性 妇女的共鸣成像（MRI）在妇女中有或有艾滋病毒感染风险。 机构间艾滋病毒研究（WIHS）评估血浆年龄与心肌异常的关系 这种高危人群的力学和纤维化。对于AIM 2和3，该项目将使 肾小球滤过的串行测量和标准化确定性的可用性 来自中年对老年人的心血管事件来自多民族研究 动脉粥样硬化（MESA）研究血浆年龄与进展 慢性肾脏疾病和事件心血管疾病。这些研究将为受训者提供 通过对临床和流行病学研究的一系列暴露，使其发展为 调查人员。此外，可用性遗传/基因组，表观基因组，转录组和代谢组学 MESA中的数据将允许探索年龄水平的OMIC相关性，为 将来进行大规模调查。因此，正式课程的结合， 增加指导性，并利用现有研究基础设施来解决研究 重大临床重要性的问题将为候选人提供更多的能力 精确医学，为受训者的成长提供机会 研究人员和其他学科。