Metabolomic Profiles and the Risk of Incident Heart Failure

项目摘要/摘要 这项提案提出了一个为期两年的研究奖学金计划，重点是代谢组谱的研究。 以及社区发生心力衰竭的风险。这项提议的目的是阐明受扰者的作用 新陈代谢在心力衰竭发展中的作用试图揭示疾病的新机制 发展。这位候选人目前是以色列贝丝医院的心血管临床和研究员 女执事医学中心和哈佛医学院。奖学金计划将需要专门的培训 通过实验室工作和教学相结合的方式在代谢组学和生物信息学方面的研究，包括 完成哈佛医学院生物医学信息学硕士课程(MBI)。这次培训将 为应聘者提供必要的技能和专业知识以过渡到职业发展奖。这个 候选人的导师罗伯特·E·格兹滕博士是代谢组学研究的领先专家， 他还领导了大规模流行病学队列中的多组谱研究。这个 候选人有一个多样化和杰出的合作者群体，并位于一个丰富的学术机构 环境，为他在团契期间取得成功提供必要的资源。 心脏和外周代谢过程受损，包括能量代谢严重不足 描述心力衰竭状态。然而，目前尚不清楚这些新陈代谢变化的程度 在疾病发生前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，它允许对 并在多年前阐明了心脏代谢性疾病的新关联和新机制 疾病发作。在关于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。 杰克逊心脏研究中的意外心力衰竭。我们的目标是将分析范围扩大到300种 在我们的平台上进行测量，以调查代谢变化的关联，包括受损的脂肪 酸氧化与心肌肥厚和发生心力衰竭(目标1和2)。此外，申请人将 确定发生心力衰竭并保留射血分数(HFpEF)和心脏的个体 射血分数降低的衰竭(HFrEF)在发病前具有明显的代谢特征(AIM 3)。这项拟议的研究旨在确定代谢变化与 心力衰竭的发展，以努力提高对疾病机制的了解。 好了！ 好了！

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. ! !