Aim: Galectin-3 (Gal-3) is a biomarker of atrial fibrillation (AF) that mediates atrial inflammation. CD98 is the membrane surface receptor for Gal-3. Nevertheless, the role of the Gal-3/CD98 axis in atrial arrhythmogenesis is unclear. In this study, we investigated the effects of Gal-3/CD98 signalling on atrial pathogenesis. Methods: Whole cell patch clamp and western blotting were used to analyse calcium/potassium homeostasis and calcium-related signalling in Gal-3-administrated HL-1 atrial cardiomyocytes with/without CD98 neutralized antibodies. Telemetry electrocardiographic recording, Masson's trichrome staining and immunohistochemistry staining of atrium were obtained from mice having received tail-vein injections with Gal-3. Results: Gal-3-treated HL-1 myocytes had a shorter action potential duration, smaller L-type calcium current, increased sarcoplasmic reticulum (SR) calcium content, Na+/Ca2+ exchanger (NCX) current, transient outward potassium current, and ultrarapid delayed rectifier potassium current than control cells had. Gal-3-treated HL-1 myocytes had greater levels of SR Ca2+ATPase, NCX, Nav1.5, and NLR family pyrin domain containing 3 (NLRP3) expression and increased calcium/calmodulin-dependent protein kinase II (CaMKII), ryanodine receptor 2 (RyR2), and nuclear factor kappa B (NF-κB) phosphorylation than control cells had. Gal-3-mediated activation of CaMKII/RyR2 pathway was diminished in the cotreatment of anti-CD98 antibodies. Mice that were injected with Gal-3 had more atrial ectopic beats, increased atrial fibrosis, and activated NF-κB/NLRP3 signalling than did control mice (nonspecific immunoglobulin) or mice treated with Gal-3 and anti-CD98 antibodies. Conclusion: Gal-3 recombinant protein administration increases atrial fibrosis and arrhythmogenesis through CD98 signalling. Targeting Gal-3/CD98 axis might be a novel therapeutic strategy for patients with AF and high Gal-3 levels.

Original languageEnglish
Article numbere13784
JournalActa Physiologica
Issue number3
Publication statusPublished - Mar 2022


  • atrial ectopy
  • calcium homeostasis
  • CaMKII
  • CD98
  • galectin-3
  • RyR2

ASJC Scopus subject areas

  • Physiology


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