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
- 批准号:10096986
- 负责人:
- 金额:$ 72.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-02-01 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdipose tissueAdrenergic ReceptorAffectAgeAmericanAnti-Arrhythmia AgentsArrhythmiaAtherosclerosisAtrial FibrillationBiological MarkersBiopsyBloodBlood specimenBody Weight decreasedBranched-Chain Amino AcidsCalcium SignalingCardiacCardiac Surgery proceduresCardiac ablationCardiologyCatecholaminesCell AdhesionClinicalClinical DataCollagenCommunicationCoronaryDataDefectDevelopmentDiagnosticDiseaseEnrollmentEnzymesEthnic OriginEthnic groupEvaluationFasciaFatty acid glycerol estersFibrosisGenesGoalsHealth ExpendituresHeartHeart AtriumHispanicsImageIncidenceIndividualInflammationInflammatoryInterleukin-6JournalsKnowledgeLeftLeft Atrial FunctionLinkLipoproteinsLongitudinal StudiesMatrix MetalloproteinasesMeasuresMediator of activation proteinMetabolismMetabolite InteractionMulti-Ethnic Study of AtherosclerosisMuscarinic Acetylcholine ReceptorMyopathyNatriuretic PeptidesObesityOutpatientsOxidative PhosphorylationOxidative StressPathogenesisPathogenicityPathway interactionsPatientsPericardial body locationPeripheralPlasmaPlayPreventionProcessProteinsProteomeProteomicsPublishingRNA SplicingRaceRecurrenceRiskRoleSignal PathwaySinusState-of-the-Art ReviewsStructureTechniquesTestingThrombosisTissuesTranscriptUnited StatesUntranslated RNAUp-RegulationValidationVariantVascular blood supplyX-Ray Computed Tomographyactivin Aadipokinesattenuationbasecollegediagnostic platformeffective therapyethnic differenceheart rhythmimprovedinsightinterestlifetime riskmetabolomemetabolomicsmulti-racialmultiple omicsnovelnovel diagnosticsnovel strategiesnovel therapeutic interventionpersonalized medicineracial and ethnicracial differencereceptor functionsubcutaneoustherapeutic targettranscriptometranscriptome sequencingtranscriptomicsvalidation studies
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)
专利数量(0)
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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:
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
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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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