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Atrial fibrillation rhythm is associated with marked changes in metabolic and myofibrillar protein expression in left atrial appendage.

Authors
  • Rennison, Julie H1
  • Li, Ling2
  • Lin, Cheryl R1
  • Lovano, Beth S1
  • Castel, Laurie1
  • Wass, Sojin Youn3
  • Cantlay, Catherine C1
  • McHale, Meghan1
  • Gillinov, A Marc4
  • Mehra, Reena1, 5, 6
  • Willard, Belinda B2
  • Smith, Jonathan D1, 6, 3
  • Chung, Mina K1, 6, 3
  • Barnard, John6, 7
  • Van Wagoner, David R8, 9, 10
  • 1 Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, 9500 Euclid Avenue, M/S ND50, Cleveland, OH, 44195, USA.
  • 2 Proteomics Research Core Services, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
  • 3 Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
  • 4 Department of Cardiothoracic Surgery, Cleveland Clinic, Cleveland, OH, 44195, USA.
  • 5 Sleep Center, Respiratory Institute, Cleveland Clinic, Cleveland, OH, 44195, USA.
  • 6 Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland, OH, 44195, USA.
  • 7 Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, 44195, USA.
  • 8 Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, 9500 Euclid Avenue, M/S ND50, Cleveland, OH, 44195, USA. [email protected]
  • 9 Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland Clinic, Cleveland, OH, 44195, USA. [email protected]
  • 10 Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH, 44195, USA. [email protected]
Type
Published Article
Journal
Pflügers Archiv - European Journal of Physiology
Publisher
Springer-Verlag
Publication Date
Jan 16, 2021
Identifiers
DOI: 10.1007/s00424-021-02514-5
PMID: 33454842
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Atrial fibrillation (AF) is strongly associated with risk of stroke and heart failure. AF promotes atrial remodeling that increases risk of stroke due to left atrial thrombogenesis, and increases energy demand to support high rate electrical activity and muscle contraction. While many transcriptomic studies have assessed AF-related changes in mRNA abundance, fewer studies have assessed proteomic changes. We performed a proteomic analysis on left atrial appendage (LAA) tissues from 12 patients with a history of AF undergoing elective surgery; atrial rhythm was documented at time of surgery. Proteomic analysis was performed using liquid chromatography with mass spectrometry (LC/MS-MS). Data-dependent analysis identified 3090 unique proteins, with 408 differentially expressed between sinus rhythm and AF. Ingenuity Pathway Analysis of differentially expressed proteins identified mitochondrial dysfunction, oxidative phosphorylation, and sirtuin signaling among the most affected pathways. Increased abundance of electron transport chain (ETC) proteins in AF was accompanied by decreased expression of ETC complex assembly factors, tricarboxylic acid cycle proteins, and other key metabolic modulators. Discordant changes were also evident in the contractile unit with both up and downregulation of key components. Similar pathways were affected in a comparison of patients with a history of persistent vs. paroxysmal AF, presenting for surgery in sinus rhythm. Together, these data suggest that while the LAA attempts to meet the energetic demands of AF, an uncoordinated response may reduce ATP availability, contribute to tissue contractile and electrophysiologic heterogeneity, and promote a progression of AF from paroxysmal episodes to development of a substrate amenable to persistent arrhythmia.

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