Advanced Glycation Endproducts and Cardio-Renal Disease

项目总结/摘要 目前的申请提出，以病人为导向， 通过组学科学和导师制的正规培训，通过提高 指导年轻的研究人员，并通过一个研究项目，将建立在 候选人以前的工作，并提供机会，发展他的组学研究portolio。的 研究项目旨在缩小关于关键先进技术的重要性的知识差距 糖基化终产物（AGEs）与心血管和肾脏疾病的关系。到 为此，它将对由主要等离子体组成的面板进行金标准测量 AGEs，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-脱氧葡萄糖酮-氢咪唑酮（3DG-H），它们具有 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，项目 将利用一项正在进行的研究， 在女性艾滋病毒感染者或有感染风险的女性中， 跨机构HIV研究（WIHS）评估血浆AGEs与心肌异常的关系 力学和纤维化的风险。对于目标2和3，该项目将利用 肾小球滤过系列测量的可用性和标准化确定 多种族研究中中年至老年人的心血管事件 动脉粥样硬化（梅萨）研究血浆AGEs与动脉粥样硬化进展的关系。 慢性肾病和心血管疾病。这些研究将为学员提供 通过一系列的临床和流行病学研究， investigators.此外，遗传学/基因组学、表观基因组学、转录组学和代谢组学 梅萨中的数据将允许探索年龄水平的组学相关性，为 未来更大规模的调查。因此，正式课程的结合， 加强指导，并利用现有的研究基础设施，以解决研究 具有重大临床意义的问题将为候选人提供更高的能力， POR在精准医学，并为他的学员的成长提供机会， 研究人员在这个和其他学科。

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.