title: Combined metabolomic and proteomic analysis of human atrial fibrillation.
abstract: OBJECTIVE
  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.
authors.affiliation: Cardiovascular Division, King's College, London, United Kingdom. manuel.mayr@kcl.ac.uk
authors.forename: Manuel
authors.initials: M
authors.lastname: Mayr
authors.forename: Shamil
authors.initials: S
authors.lastname: Yusuf
authors.forename: Graeme
authors.initials: G
authors.lastname: Weir
authors.forename: Yuen-Li
authors.initials: YL
authors.lastname: Chung
authors.forename: Ursula
authors.initials: U
authors.lastname: Mayr
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Yin
authors.forename: Christophe
authors.initials: C
authors.lastname: Ladroue
authors.forename: Basetti
authors.initials: B
authors.lastname: Madhu
authors.forename: Neil
authors.initials: N
authors.lastname: Roberts
authors.forename: Ayesha
authors.initials: A
authors.lastname: De Souza
authors.forename: Salim
authors.initials: S
authors.lastname: Fredericks
authors.forename: Marion
authors.initials: M
authors.lastname: Stubbs
authors.forename: John R
authors.initials: JR
authors.lastname: Griffiths
authors.forename: Marjan
authors.initials: M
authors.lastname: Jahangiri
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
authors.forename: A John
authors.initials: AJ
authors.lastname: Camm
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000378:metabolism*; D001281:Atrial Fibrillation / Q000209:etiology / Q000378:metabolism*; D015256:Coenzyme A-Transferases / Q000378:metabolism*; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000150:complications / Q000378:metabolism / Q000601:surgery; D006801:Humans; D007657:Ketone Bodies / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D011183:Postoperative Complications / Q000209:etiology / Q000378:metabolism; D040901:Proteomics
chemical_list: D007657:Ketone Bodies; D015256:Coenzyme A-Transferases; C021460:3-ketoacid CoA-transferase; D020155:3-Hydroxybutyric Acid