Differential left-to-right atria gene expression ratio in human sinus rhythm and atrial fibrillation: Implications for arrhythmogenesis and thrombogenesis

Feng Chun Tsai, Yen Chen Lin, Shang Hung Chang, Gwo Jyh Chang, Yu Juei Hsu, Yuan Min Lin, Yun Shien Lee, Chun Li Wang, Yung Hsin Yeh*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

40 Scopus citations

Abstract

Background Atrial fibrillation (AF) causes atrial remodeling, and the left atrium (LA) is the favored substrate for maintaining AF. It remains unclear if AF remodels both atria differently and contributes to LA arrhythmogenesis and thrombogenesis. Therefore, we wished to characterize the transcript profiles in the LA and right atrium (RA) in sinus rhythm (SR) and AF respectively. Methods Paired LA and RA appendages acquired from patients receiving cardiac surgery were used for ion-channel- and whole-exome-based transcriptome analysis. The ultrastructure was evaluated by immunohistochemistry. Results Twenty-two and twenty ion-channels and transporters were differentially expressed between the LA and RA in AF and SR, respectively. Among these, 15 genes were differentially expressed in parallel between AF and SR. AF was associated with increased LA/RA expression ratio in 9 ion channel-related genes, including genes related to calcium handling. In microarray, AF was associated with a differential LA/RA gene expression ratio in 309 genes, and was involved in atherosclerosis-related signaling. AF was associated with the upregulation of thrombogenesis-related genes in the LA appendage, including P2Y12, CD 36 and ApoE. Immunohistochemistry showed higher expressions of collagen-1, oxidative stress and TGF-β1 in the RA compared to the LA. Conclusions AF was associated with differential LA-to-RA gene expression related to specific ion channels and pathways as well as upregulation of thrombogenesis-related genes in the LA appendage. Targeting the molecular mechanisms underlying the LA-to-RA difference and AF-related remodeling in the LA appendage may help provide new therapeutic options in treating AF and preventing thromboembolism in AF.

Original languageEnglish
Pages (from-to)104-112
Number of pages9
JournalInternational Journal of Cardiology
Volume222
DOIs
StatePublished - 01 11 2016

Bibliographical note

Publisher Copyright:
© 2016

Keywords

  • Atrial fibrillation
  • Atrium
  • Ion channel
  • Microarray

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