title: Galectin-3 Regulates Atrial Fibrillation Remodeling and Predicts Catheter Ablation Outcomes.
abstract: To determine whether Gal-3 mediates sustained atrial fibrillation (AF)-induced atrial structural and electrical remodeling and contributes to AF perpetuation.
  
  
  
  Galectin-3 (Gal-3) mediates extracellular matrix remodeling in heart failure, but its role in AF progression remains unexplored.
  
  
  
  We examined intracardiac blood samples from patients with AF (N=55) to identify potential biomarkers of AF recurrence. In a sheep model of tachypacing-induced AF (N=20), we tested the effects of Gal-3 inhibition during AF progression.
  
  
  
  In patients, intracardiac serum Gal-3 levels were greater in persistent than paroxysmal AF and independently predicted atrial tachyarrhythmia recurrences after a single ablation procedure. In the sheep model, both Gal-3 and TGF-β1 were elevated in the atria of persistent AF animals. The Gal-3 inhibitor GM-CT-01 (GMCT) reduced both Gal-3 and TGF-β1-induced sheep atrial fibroblast migration and proliferationin vitro. GMCT (12 mg/kg twice/week) prevented the increase in serum procollagen type III N-terminal peptide seen during progression to persistent AF, and also mitigated atrial dilatation, myocyte hypertrophy, fibrosis, and the expected increase in dominant frequency of excitation. Atria of GMCT-treated animals had significantly less TGF-β1-Smad2/3 signaling pathway activation and expression of α-smooth muscle actin and collagen than saline-treated animals.Ex-vivohearts from GMCT-treated animals had significantly longer action potential durations and fewer rotors and wavebreaks during AF, and myocytes had lower functional expression of inward rectifier K+channel (Kir2.3) than saline-treated animals. Importantly, GMCT increased the probability of spontaneous AF termination, decreased AF inducibility and reduced overall AF burden.
  
  
  
  Inhibiting Gal-3 during AF progression might be useful as an adjuvant treatment to improve outcomes of catheter ablation for persistent AF. Gal-3 inhibition may be a potential new upstream therapy for prevention of AF progression.
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Takemoto
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: Rafael J
authors.initials: RJ
authors.lastname: Ramirez
authors.affiliation: Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor, MI.
authors.forename: Miki
authors.initials: M
authors.lastname: Yokokawa
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: Kuljeet
authors.initials: K
authors.lastname: Kaur
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ponce-Balbuena
authors.affiliation: Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor, MI.
authors.forename: Mohamad C
authors.initials: MC
authors.lastname: Sinno
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: B Cicero
authors.initials: BC
authors.lastname: Willis
authors.affiliation: Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor, MI.
authors.forename: Hamid
authors.initials: H
authors.lastname: Ghanbari
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Ennis
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Guerrero-Serna
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: Bettina C
authors.initials: BC
authors.lastname: Henzi
authors.affiliation: Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor, MI.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Latchamsetty
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ramos-Mondragon
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: Hassan
authors.initials: H
authors.lastname: Musa
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: Raphael P
authors.initials: RP
authors.lastname: Martins
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: Sandeep V
authors.initials: SV
authors.lastname: Pandit
authors.affiliation: Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA.
authors.forename: Sami F
authors.initials: SF
authors.lastname: Noujaim
authors.affiliation: Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor, MI.
authors.forename: Thomas
authors.initials: T
authors.lastname: Crawford
authors.affiliation: Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor, MI.
authors.forename: Krit
authors.initials: K
authors.lastname: Jongnarangsin
authors.affiliation: Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor, MI.
authors.forename: Frank
authors.initials: F
authors.lastname: Pelosi
authors.affiliation: Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor, MI.
authors.forename: Frank
authors.initials: F
authors.lastname: Bogun
authors.affiliation: Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor, MI.
authors.forename: Aman
authors.initials: A
authors.lastname: Chugh
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: Omer
authors.initials: O
authors.lastname: Berenfeld
authors.affiliation: Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor, MI.
authors.forename: Fred
authors.initials: F
authors.lastname: Morady
authors.affiliation: Division of Cardiovascular Medicine, Cardiac Arrhythmia Service, University of Michigan, Ann Arbor, MI.
authors.forename: Hakan
authors.initials: H
authors.lastname: Oral
authors.affiliation: Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI.
authors.forename: José
authors.initials: J
authors.lastname: Jalife
keywords: Atrial fibrillation; Catheter ablation; Fibrosis; Galectin-3; Upstream therapy