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.

项目总结/文摘