Plasma Metabolomics and Myocardial Energetics in Heart Failure

心力衰竭的血浆代谢组学和心肌能量学

基本信息

批准号：
9900043
负责人：
David E Lanfear
金额：
$ 76.33万
依托单位：
HENRY FORD HEALTH SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-15 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9900043
关键词：
Acetates Address Animal Model Animals Biological Biological Markers Blood Brain natriuretic peptide Canis familiaris Cardiac Cell Respiration Clinical Cohort Studies Data Development Disease Disease Progression EFRAC Energy Metabolism Focus Groups Genes Genetic Genomics Genotype Heart Heart failure Heritability Hospitals Human Impairment Individual Infrastructure Interdisciplinary Study Intervention Intervention Studies Investigation Laboratories Lead Link Measures Metabolic Metabolic Pathway Metabolism Methods Mitochondria Modeling Myocardial Myocardial dysfunction Myocardium Natural History Pathway interactions Patients Peripheral Pharmacotherapy Phenotype Plasma Positron-Emission Tomography Public Health Risk Sampling Series Severity of illness Source Specific qualifier value Structure Subgroup Technology Testing Validation Variant Work clinical development clinical phenotype cohesion cohort disease heterogeneity follow-up genome-wide improved outcome in vivo interest metabolomics novel novel therapeutics outcome forecast personalized medicine precision medicine response survival prediction tool treatment response treatment strategy

项目摘要

ABSTRACT Heart failure (HF) remains an enormous public health problem despite advances in treatment. Disease progression and response to therapy in HF varies widely between individuals, but breakthrough technologies such as genomics and metabolomics are helping to unravel the disease heterogeneity that confounds patient management. Perturbed energy metabolism may be a key contributor to cardiac dysfunction and the development of clinical HF. Evidence from a variety of sources indicates that impaired structure and function of the energetic apparatus in the myocardium contributes to disease severity, progression, and may influence response to treatment. However, in order to advance these observations toward meaningful interventions for HF patients, several key steps are still needed: 1) confirming the importance of metabolic variation in human HF, 2) developing noninvasive markers of myocardial energetic status, and 3) identifying promising targets for intervention. Our proposed project is a series of interwoven translational investigations in humans and dogs with HF to define the association of plasma metabolite levels with disease severity, myocardial energetics, and disease progression. This project leverages substantial infrastructure already in place a large existing genetic cohort study, available plasma samples suitable for metabolomic profiling, comprehensive translational laboratory capabilities, and a cohesive multidisciplinary research group focused on HF. Together the planned studies will address the overarching hypothesis that the peripheral metabolomic signature can indicate disease progression/treatment responsiveness in HF patients and that this is driven by altered myocardial energy metabolism. If true, then these data will help advance personalized therapy and identify novel targets for HF intervention, leading to improved outcomes for HF patients.

抽象的尽管治疗方法取得了进步，心力衰竭（HF）仍然是一个巨大的公共卫生问题。疾病心力衰竭的进展和治疗反应因人而异，但突破性技术基因组学和代谢组学等技术正在帮助揭示困扰患者的疾病异质性管理。能量代谢紊乱可能是导致心脏功能障碍的一个关键因素临床心力衰竭的发展。来自各种来源的证据表明，结构和功能受损心肌能量装置的变化有助于疾病的严重程度、进展，并可能影响对治疗的反应。然而，为了将这些观察结果推向有意义的干预措施对于心力衰竭患者，仍需要几个关键步骤：1）确认人体代谢变异的重要性心力衰竭，2) 开发心肌能量状态的无创标记物，以及 3) 确定有希望的目标干涉。我们提出的项目是对人类和狗进行一系列相互交织的转化研究与 HF 来定义血浆代谢水平与疾病严重程度、心肌能量学和疾病进展。该项目利用了现有的大量基础设施队列研究、适用于代谢组学分析的可用血浆样本、综合转化实验室能力，以及一个专注于高频的有凝聚力的多学科研究小组。一起计划的研究将解决外周代谢组学特征可以指示疾病的总体假设心力衰竭患者的进展/治疗反应，这是由心肌能量改变驱动的代谢。如果属实，那么这些数据将有助于推进个性化治疗并确定心力衰竭的新靶点干预，从而改善心衰患者的预后。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Prognostic value of circulating microRNAs on heart failure-related morbidity and mortality in two large diverse cohorts of general heart failure patients.

循环 microRNA 对两个大型不同普通心力衰竭患者队列中心力衰竭相关发病率和死亡率的预后价值。

DOI：
发表时间：
2018
期刊：
影响因子：
18.2
作者：
Bayés;Lanfear, David E;de Ronde, Maurice W J;Lupón, Josep;Leenders, Joost J;Liu, Zhen;Zuithoff, Nicolaas P A;Eijkemans, Marinus J C;Zamora, Elisabet;De Antonio, Marta;Zwinderman, Aeilko H;Pinto;Pinto, Yigal M
通讯作者：
Pinto, Yigal M

Genetics of heart rate in heart failure patients (GenHRate).

心力衰竭患者心率遗传学（GenHRate）。

DOI：
发表时间：
2019
期刊：
影响因子：
4.5
作者：
Evans, Kaleigh L;Wirtz, Heidi S;Li, Jia;She, Ruicong;Maya, Juan;Gui, Hongsheng;Hamer, Andrew;Depre, Christophe;Lanfear, David E
通讯作者：
Lanfear, David E

Effects of Intravenous Infusion of Vepoloxamer on Left Ventricular Function in Dogs with Advanced Heart Failure.

静脉输注维泊洛沙姆对晚期心力衰竭犬左心室功能的影响。