Combined Metabolomic and Proteomic Analysis of Human Atrial Fibrillation Academic Article uri icon

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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.

authors

  • Mayr, Manuel
  • Yusuf, Salim
  • Weir, Graeme
  • Chung, Yuen-Li
  • Mayr, Ursula
  • Yin, Xiaoke
  • Ladroue, Christophe
  • Madhu, Basetti
  • Roberts, Neil
  • De Souza, Ayesha
  • Fredericks, Salim
  • Stubbs, Marion
  • Griffiths, John R
  • Jahangiri, Marjan
  • Xu, Qingbo
  • Camm, A John

publication date

  • February 2008