Molecular signatures of sinus node dysfunction induce structural remodeling in the right atrial tissue

Seung Young Roh, Ji Yeon Kim, Hyo Kyeong Cha, Hye Young Lim, Youngran Park, Kwang No Lee, Jaemin Shim, Jong Il Choi, Young Hoon Kim, Gi Hoon Son

Research output: Contribution to journalArticlepeer-review

Abstract

The sinus node (SN) is located at the apex of the cardiac conduction system, and SN dysfunction (SND)—characterized by electrical remodeling—is generally attributed to idiopathic fibrosis or ischemic injuries in the SN. SND is associated with increased risk of cardiovascular disorders, including syncope, heart failure, and atrial arrhythmias, particularly atrial fibrillation. One of the histological SND hallmarks is degenerative atrial remodeling that is associated with conducti on abnormal i ti es and i ncreased ri ght atri al refractoriness. Although SND is frequently accompanied by increased fibrosis in the right atrium (RA), its molecular basis still remains elusive. Therefore, we investigated whether SND can induce significant molecular changes that account for the structural remodeling of RA. Towards this, we employed a rabbit model of experimental SND, and then compared the genome-wide RNA expression profiles in RA between SND-induced rabbits and sham-operated controls to identify the differentially expressed transcripts. The accompanying gene enrichment analysis revealed extensive pro-fibrotic changes within 7 days after the SN ablation, including activation of transforming growth factor-β (TGF-β) signaling and alterations in the levels of extracellular matrix components and their regulators. Importantly, our findings suggest that periostin, a matricellular factor that regulates the development of cardiac tissue, might play a key role in mediating TGF-β-signaling-induced aberrant atrial remodeling. In conclusion, the present study provides valuable information regarding the molecular signatures underlying SND-induced atrial remodeling, and indicates that periostin can be potentially used in the diagnosis of fibroproliferative cardiac dysfunctions.

Original languageEnglish
Pages (from-to)408-418
Number of pages11
JournalMolecules and cells
Volume43
Issue number4
DOIs
Publication statusPublished - 2020

Keywords

  • Cardiac fibrosis
  • Periostin
  • Right atrium
  • Sinus node dysfunction
  • Transcriptome
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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