下调和上调
心房颤动
内科学
生物
信号转导
基因表达
基因表达调控
内分泌学
基因
细胞生物学
医学
遗传学
作者
Chien Lung Chen,Jiunn Lee Lin,Ling‐Ping Lai,Chun Pan,Shoei K. Stephen Huang,Chih Sheng Lin
标识
DOI:10.1016/j.bbadis.2006.10.017
摘要
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-beta (TGF-beta)-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-beta signaling and the upregulated TGF-beta1 and -beta2 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 beta-adrenergic and TGF-beta signaling.
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