Altered expression of FHL1, CARP, TSC-22 and P311 provide insights into complex transcriptional regulation in pacing-induced atrial fibrillation

Chien Lung Chen, Jiunn Lee Lin, Ling Ping Lai, Chun Hsu Pan, Shoei K Stephen Huang, Chih Sheng Lin

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Atrial fibrillation (AF) is the most common progressive disease in patients with cardiac arrhythmia. AF is accompanied by complex atrial remodeling and changes in gene expression, but only a limited number of transcriptional regulators have been identified. Using a low-density cDNA array, we identified 31 genes involved in transcriptional regulation, signal transduction or structural components, which were either significantly upregulated or downregulated in porcine atria with fibrillation (induced by rapid atrial pacing at a rate of 400-600 bpm for 4 weeks that was then maintained without pacing for 2 weeks). The genes for four and a half LIM domains protein-1 (FHL1), transforming growth factor-β (TGF-β)-stimulated clone 22 (TSC-22), and cardiac ankyrin repeat protein (CARP) were significantly upregulated, and chromosome 5 open reading frame gene 13 (P311) was downregulated in the fibrillating atria. FHL1 and CARP play important regulatory roles in cardiac remodeling by transcriptional regulation and myofilament assembly. Induced mRNA expression of both FHL1 and CARP was also observed when cardiac H9c2 cells were treated with an adrenergic agonist. Increasing TSC-22 and marked P311 deficiency could enhance the activity of TGF-β signaling and the upregulated TGF-β1 and -β2 expressions were identified in the fibrillating atria. These results implicate that observed alterations of underlying molecular events were involved in the rapid-pacing induced AF, possibly via activation of the β-adrenergic and TGF-β signaling.

Original languageEnglish
Pages (from-to)317-329
Number of pages13
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1772
Issue number3
DOIs
Publication statusPublished - Mar 2007
Externally publishedYes

Keywords

  • Atrial fibrillation
  • Low-density cDNA array
  • Transcriptional regulator
  • Transforming growth factor-β signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Biophysics

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