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Combined metabolomic and proteomic analysis of human atrial fibrillation.

Abstract：

OBJECTIVES:We sought to decipher metabolic processes servicing the increased energy demand during persistent atrial fibrillation (AF) and to ascertain whether metabolic derangements might instigate this arrhythmia. BACKGROUND:Whereas electrical, structural, and contractile remodeling processes are well-recognized contributors to the self-perpetuating nature of AF, the impact of cardiac metabolism upon the persistence/initiation of this resilient arrhythmia has not been explored in detail. METHODS:Human atrial appendage tissues from matched cohorts in sinus rhythm (SR), from those who developed AF post-operatively, and from patients in persistent AF undergoing cardiac surgery were analyzed using a combined metabolomic and proteomic approach. RESULTS:High-resolution proton nuclear magnetic resonance (NMR) spectroscopy of cardiac tissue from patients in persistent AF revealed a rise in beta-hydroxybutyrate, the major substrate in ketone body metabolism, along with an increase in ketogenic amino acids and glycine. These metabolomic findings were substantiated by proteomic experiments demonstrating differential expression of 3-oxoacid transferase, the key enzyme for ketolytic energy production. Notably, compared with the SR cohort, the group susceptible to post-operative AF showed a discordant regulation of energy metabolites. Combined principal component and linear discriminant analyses of metabolic profiles from proton NMR spectroscopy correctly classified more than 80% of patients at risk of AF at the time of coronary artery bypass grafting. CONCLUSIONS:The present study characterized the metabolic adaptation to persistent AF, unraveling a potential role for ketone bodies, and demonstrated that discordant metabolic alterations are evident in individuals susceptible to post-operative AF.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Mayr M,Yusuf S,Weir G,Chung YL,Mayr U,Yin X,Ladroue C,Madhu B,Roberts N,De Souza A,Fredericks S,Stubbs M,Griffiths JR,Jahangiri M,Xu Q,Camm AJ

doi

10.1016/j.jacc.2007.09.055

subject

Has Abstract

pub_date

2008-02-05 00:00:00

pages

585-94

issue

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(07)03611-X

journal_volume

pub_type

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Combined metabolomic and proteomic analysis of human atrial fibrillation.