TY - JOUR
T1 - Altered expression of FHL1, CARP, TSC-22 and P311 provide insights into complex transcriptional regulation in pacing-induced atrial fibrillation
AU - Chen, Chien Lung
AU - Lin, Jiunn Lee
AU - Lai, Ling Ping
AU - Pan, Chun Hsu
AU - Huang, Shoei K Stephen
AU - Lin, Chih Sheng
N1 - Funding Information:
This work was supported by the grants of NSC 92-2314-B-009-001-B32 and NSC 93-2314-B-009-001-B32 from the National Science Council and the grants of VGHUST93-G5-05-4 and VGHUST94-G5-05-4 from the Veterans General Hospitals, University System of Taiwan, Taiwan.
PY - 2007/3
Y1 - 2007/3
N2 - 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.
AB - 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.
KW - Atrial fibrillation
KW - Low-density cDNA array
KW - Transcriptional regulator
KW - Transforming growth factor-β signaling
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U2 - 10.1016/j.bbadis.2006.10.017
DO - 10.1016/j.bbadis.2006.10.017
M3 - Article
C2 - 17174532
AN - SCOPUS:33847039932
SN - 0925-4439
VL - 1772
SP - 317
EP - 329
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 3
ER -