Metabolomic Profiles and the Risk of Incident Heart Failure

代谢组学特征和心力衰竭事件的风险

• 批准号: 9908569
• 负责人: Usman A. Tahir
• 金额: $ 6.48万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-12-03 至 2020-07-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9908569
• 关键词: Affect; African American; Bioinformatics; Cardiac; Cardiac development; Cardiovascular system; Clinical Research; Cohort Studies; Communities; Complex; Coronary heart disease; Cross-Sectional Studies; Data; Development; Diabetes Mellitus; Disease; EFRAC; Echocardiography; Energy Metabolism; Environment; Epidemiology; Failure; Fellowship; Fellowship Program; Functional disorder; Healthcare; Heart Hypertrophy; Heart failure; Heterogeneity; Impairment; Individual; Investigation; Israel; Jackson Heart Study; K-Series Research Career Programs; Laboratories; Lead; Left Ventricular Hypertrophy; Longevity; Measurement; Measures; Medical center; Mentors; Metabolic; Metabolic Diseases; Metabolic dysfunction; Metabolism; Molecular; Morbidity - disease rate; Motivation; Myocardial; Myocardial dysfunction; Nature; Onset of illness; Pathway interactions; Patients; Peripheral; Phenotype; Plasma; Population; Prevalence; Research; Resources; Risk; Risk Factors; Risk stratification; Role; Syndrome; Training; Work; acylcarnitine; aging population; biomedical informatics; cardiogenesis; cardiometabolism; cardiovascular risk factor; clinical phenotype; cohort; disorder risk; fatty acid oxidation; improved; insight; medical schools; metabolic abnormality assessment; metabolomics; mortality; multiple omics; new therapeutic target; novel; novel therapeutics; oxidation; preservation; programs; skills; small molecule; structural heart disease; success; targeted treatment; therapeutic target; tool; trait; urea cycle

Project Summary/Abstract This proposal presents a 2-year research fellowship program focused on the study of metabolomic profiling and risk of incident heart failure in the community. The aim of the proposal is to elucidate the role of disturbed metabolism in the development of heart failure in an attempt to uncover novel mechanisms of disease development. The candidate is currently a cardiovascular clinical and research fellow at the Beth Israel Deaconess Medical Center and Harvard Medical School. The fellowship program will entail dedicated training in metabolomic profiling and bioinformatics through a combination of laboratory work and didactics including completion of a Master of Biomedical Informatics Program at Harvard Medical School (MBI). This training will provide the candidate the necessary skill set and expertise to transition to a career development award. The candidate's mentor, Dr. Robert E. Gerszten, is a leading expert in the study of metabolomics and cardiometabolic disease and has led studies of multi-omic profiling in large-scale epidemiological cohorts. The candidate has a diverse and distinguished group of collaborators and is situated in a rich academic institutional environment, providing him with the necessary resources for success during his fellowship. Impaired cardiac and peripheral metabolic processes including significant deficiencies in energy metabolism characterize the heart failure state. However, its unclear to the extent to which these metabolic alterations are present and contribute to the development of heart failure prior to the onset of disease. The emerging field of metabolomics, the study of small molecules or metabolites, allows for deep interrogation of disturbed metabolism and has elucidated novel associations and mechanisms of cardiometabolic disease years before disease onset. In preliminary data on a limited set of metabolites, we identify novel associations of metabolites with incident heart failure in the Jackson Heart Study. We aim to expand our analysis to 300 analytes measured on our platforms, to investigate the associations of metabolic alterations, including impaired fatty acid oxidation with cardiac hypertrophy and incident heart failure (Aims 1 and 2). Further, the applicant will determine whether individuals who develop heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) carry distinct metabolic signatures prior to onset of disease (Aim 3). The proposed research and aims to determine the association of metabolic alterations with the development of heart failure in an effort to improve understanding of the mechanisms of disease. ! !

项目概要/摘要 该提案提出了一项为期 2 年的研究奖学金计划，重点研究代谢组学分析 以及社区发生心力衰竭的风险。该提案的目的是阐明受干扰者的作用 心力衰竭发展中的代谢，试图揭示疾病的新机制 发展。该候选人目前是贝斯以色列医院的心血管临床和研究员 女执事医疗中心和哈佛医学院。研究金计划将需要专门的培训 通过实验室工作和教学相结合，进行代谢组学分析和生物信息学研究，包括 完成哈佛医学院 (MBI) 生物医学信息学硕士课程。此次培训将 为候选人提供必要的技能和专业知识，以过渡到职业发展奖。这 候选人的导师 Robert E. Gerszten 博士是代谢组学研究领域的领先专家 心脏代谢疾病，并领导了大规模流行病学队列的多组学分析研究。这 候选人拥有多元化且杰出的合作者群体，并且位于丰富的学术机构中 环境，为他在研究期间取得成功提供必要的资源。 心脏和外周代谢过程受损，包括能量代谢显着缺乏 表征心力衰竭状态。然而，目前尚不清楚这些代谢变化的影响程度 在疾病发作前就出现并促进心力衰竭的发展。新兴领域 代谢组学是对小分子或代谢物的研究，可以深入研究受干扰的物质 代谢，并在几年前阐明了心脏代谢疾病的新关联和机制 疾病发作。在一组有限代谢物的初步数据中，我们确定了代谢物的新关联 杰克逊心脏研究中发生心力衰竭。我们的目标是将分析范围扩大到 300 种分析物 在我们的平台上进行测量，以研究代谢改变的关联，包括脂肪受损 酸氧化导致心脏肥大和心力衰竭（目标 1 和 2）。此外，申请人将 确定患有射血分数保留 (HFpEF) 心力衰竭的个体是否 射血分数降低的衰竭 (HFrEF) 在疾病发作前具有明显的代谢特征（Aim 3）。拟议的研究旨在确定代谢改变与 心力衰竭的发展，以提高对疾病机制的了解。 ！ ！