Reprogramming of the human atrial transcriptome in permanent atrial fibrillation -: Expression of a ventricular-like genomic signature
Reprogramming of the human atrial transcriptome in permanent atrial fibrillation -: Expression of a ventricular-like genomic signature
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DOI：
10.1161/01.res.0000165480.82737.33
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发表时间：
2005-05-13
影响因子：
20.1
通讯作者：
Nabauer, M
中科院分区：
文献类型：
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作者：
Barth, AS;Merk, S;Nabauer, M
心房颤动与心房肌中心室肌球蛋白亚型表达增加相关，被认为是去分化过程的一部分。心房颤动时心室亚型的再表达是否仅限于编码收缩蛋白的转录本尚不清楚。因此，本研究使用Affytron U133阵列比较了永久性房颤患者的心房mRNA表达与窦性心律患者的心房mRNA表达以及心室基因表达。在心房肌中，我们确定了1434个基因在房颤中失调，其中大多数，包括钙依赖性信号通路的关键要素，显示下调。基于基因本体论的功能分类提供了结构、收缩和电生理重构的相互依赖过程的特定基因集。此外，我们首次证明了参与代谢活动的转录物的显著上调，这表明了对心房肌中代谢需求增加的适应性反应。心房纤颤中心房特异性基因表达上调的可能性是对照组的5倍（174个基因上调，35个基因下调），而心房特异性转录本主要下调（56个基因上调，564个基因下调）。总的来说，在心房肌中，发现心室肌特征性基因的功能类别上调（例如，代谢过程），而主要在心房肌中表达的功能类别下调（例如，信号转导和细胞通讯）。因此，采用心室样信号的去分化是心房收缩的一般特征。
Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether reexpression of ventricular isoforms in atrial fibrillation is restricted to transcripts encoding for contractile proteins is unknown. Therefore, this study compares atrial mRNA expression in patients with permanent atrial fibrillation to atrial mRNA expression in patients with sinus rhythm and to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed downregulation. Functional classification based on Gene Ontology provided the specific gene sets of the interdependent processes of structural, contractile, and electrophysiological remodeling. In addition, we demonstrate for the first time a prominent upregulation of transcripts involved in metabolic activities, suggesting an adaptive response to increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were 5 times more likely to be upregulated in atrial fibrillation (174 genes upregulated, 35 genes downregulated), whereas atrial-specific transcripts were predominantly downregulated (56 genes upregulated, 564 genes downregulated). Overall, in fibrillating atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be upregulated (eg, metabolic processes), whereas functional classes predominantly expressed in atrial myocardium were downregulated (eg, signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium.