Trans-omic analysis of epicardial adipose tissue in atrial fibrillation

心房颤动心外膜脂肪组织的跨组学分析

基本信息

项目摘要

Project Summary Atrial fibrillation (AF) is the most common arrhythmia affecting well over 2 million people in the US with projections that it will affect 8-12 million people by 2050. It is responsible for >$6 billion in annual health care expenditures in the United States. While catheter ablation is a somewhat effective treatment for AF, its application generates additional left atrial (LA) fibrosis, an approach that can be associated with proarrhythmia and reduction in left atrial function. Thus, it would be desirable to identify new targets for prevention and treatment of AF that focus on the underlying pathophysiologic abnormalities which may vary among patients. Obesity and epicardial adipose tissue (EAT) have been associated with AF. LAEAT, due to its contiguity to the LA, may directly influence LA substrate via profibrotic, inflammatory, and other adipocytokines. It has been shown that EAT may play an independent role in the progression, development and recurrence of AF after catheter ablation. There are known racial/ethnic differences in the incidence of AF that parallel the noted racial differences in EAT. Yet, the precise role of EAT and, in particular, LAEAT in the pathogenesis of AF is not well characterized. A 2016 State-of-the-Art review in the Journal of the American College of Cardiology noted “the integration of metabolomics with other ‘omics’ platforms will allow us to gain insight into pathophysiological interactions of metabolites, proteins, genes, and disease states, while advancing personalized medicine”. This novel approach has not been implemented in AF. The overall goal of this study is to evaluate the role of EAT and, in particular, LAEAT in the pathogenesis of AF using a multi-omic (proteome, metabolome, transcriptome) approach in order to identify novel potential diagnostics and therapeutic targets. Our specific aims are to: 1) In a multiracial/ethnic population, evaluate associations of LAEAT with plasma biomarkers known to be associated with AF. We will enroll 120 patients with AF and 120 controls from the outpatient cardiology practice – 40 white, 40 black, and 40 Hispanic in each group of both patients and controls and evaluate the effects of race/ethnicity on the relationship of LAEAT to biomarkers of fibrosis and inflammation, among others. 2) Examine the LAEAT transcriptome in patients with and without AF. We will enroll 60 patients undergoing cardiac surgery and obtain EAT biopsies for analysis for upregulation of genes encoding for factors that can promote atrial fibrosis. RNA-seq analysis will cover all aspects of the transcriptome without any prior knowledge of it, allowing for the analysis of novel transcripts, splice variants and noncoding RNAs. 3) Determine cross-sectional associations between EAT and metabolomic features derived from metabolomics of stored blood specimens in the Multi-Ethnic Study of Atherosclerosis and the Rotterdam Study and test for associations between the identified metabolites and incident AF. We will perform an external validation in the Dallas Heart Study. In the aggregate, these 3 aims will provide a novel platform for the diagnostic evaluation of AF which may enable development of targeted treatments based on addressing the pathogenesis of AF.
项目总结

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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JEFFREY J GOLDBERGER其他文献

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{{ truncateString('JEFFREY J GOLDBERGER', 18)}}的其他基金

Pathophysiological Significance of Atrial Fibrillation Electrogram Patterns
心房颤动电图模式的病理生理学意义
  • 批准号:
    10634983
  • 财政年份:
    2023
  • 资助金额:
    $ 72.59万
  • 项目类别:
Trans-omic analysis of epicardial adipose tissue in atrial fibrillation
心房颤动心外膜脂肪组织的跨组学分析
  • 批准号:
    10330560
  • 财政年份:
    2021
  • 资助金额:
    $ 72.59万
  • 项目类别:
Trans-omic analysis of epicardial adipose tissue in atrial fibrillation
心房颤动心外膜脂肪组织的跨组学分析
  • 批准号:
    10553649
  • 财政年份:
    2021
  • 资助金额:
    $ 72.59万
  • 项目类别:
Novel medical adjunctive therapy to catheter ablation for atrial fibrillation
心房颤动导管消融的新型医学辅助疗法
  • 批准号:
    10113417
  • 财政年份:
    2019
  • 资助金额:
    $ 72.59万
  • 项目类别:
Path to Improved Risk Stratification
改进风险分层的途径
  • 批准号:
    9125490
  • 财政年份:
    2016
  • 资助金额:
    $ 72.59万
  • 项目类别:
Path to Improved Risk Stratification
改进风险分层的途径
  • 批准号:
    8719852
  • 财政年份:
    2014
  • 资助金额:
    $ 72.59万
  • 项目类别:
4D Magnetic Resonance Imaging for Atrial Flow Assessment in Atrial Fibrillation
4D 磁共振成像用于心房颤动心房血流评估
  • 批准号:
    8605912
  • 财政年份:
    2013
  • 资助金额:
    $ 72.59万
  • 项目类别:
4D Magnetic Resonance Imaging for Atrial Flow Assessment in Atrial Fibrillation
4D 磁共振成像用于心房颤动心房血流评估
  • 批准号:
    8445112
  • 财政年份:
    2013
  • 资助金额:
    $ 72.59万
  • 项目类别:
PHYSIOLOGY OF HEART RATE RECOVERY AFTER SUBMAXIMAL EXERCISE IN SUBJECTS WITH CAD
CAD 受试者次极量运动后心率恢复的生理学
  • 批准号:
    7604258
  • 财政年份:
    2006
  • 资助金额:
    $ 72.59万
  • 项目类别:
INFARCT CHARACTERISTICS DETERMINED BY CARDIAC MRI PREDICTIVE OF ARRHYTHMIC EVENT
通过心脏 MRI 确定的梗塞特征预测心律失常事件
  • 批准号:
    7604307
  • 财政年份:
    2006
  • 资助金额:
    $ 72.59万
  • 项目类别:

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