Transcription profiling of human atrial and ventricular myocardium from patients atrial tissue of patients with sinus rhythm vs. human left ventricular non-failing myocardium to identify the transcriptional basis for ultrastructural and functional specialization of human atria and ventricles

Note this data set has identical data files: Files GSM40994.txt and GSM40995.txt. GSE2240 contains two different experimental subsets:; 1) Comparison of atrial and ventricular gene expression (atrial tissue of patients with sinus rhythm vs. human left ventricular non-failing myocardium); The purpose of our investigation was to identify the transcriptional basis for ultrastructural and functional specialization of human atria and ventricles. Using exploratory microarray analysis (Affymetrix U133A+B), we detected 11,740 transcripts expressed in human heart, representing the most comprehensive report of the human myocardial transcriptome to date. Variation in gene expression between atria and ventricles accounted for the largest differences in this data set, as 3.300 and 2.974 transcripts showed higher expression in atria and ventricles, respectively. Functional classification based on Gene Ontology identified chamber-specific patterns of gene expression and provided molecular insights into the regional specialization of cardiomyocytes, correlating important functional pathways to transcriptional activity: Ventricular myocytes preferentially express genes satisfying contractile and energetic requirements, while atrial myocytes exhibit specific transcriptional activities related to neurohumoral function. In addition, several pro-fibrotic and apoptotic pathways were concentrated in atrial myocardium, substantiating the higher susceptibility of atria to programmed cell death and extracellular matrix remodelling observed in human and experimental animal models of heart failure. Differences in transcriptional profiles of atrial and ventricular myocardium thus provide molecular insights into myocardial cell diversity and distinct region-specific adaptations to physiological and pathophysiological conditions (Barth AS et al., Eur J Physiol, 2005). 2) Comparison of atrial gene expression in patients with permanent atrial fibrillation and sinus rhythm. Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether re-expression 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 of patients with sinus rhythm as well as to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1.434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed down-regulation. 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 up-regulation of transcripts involved in metabolic activities, suggesting an adaptive response to an increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were five times more likely to be up-regulated in atrial fibrillation (174 genes up-regulated, 35 genes down-regulated), while atrial-specific transcripts were predominantly down-regulated (56 genes up-regulated, 564 genes down-regulated). Overall, in atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be up-regulated (e.g. metabolic processes) while functional classes predominantly expressed in atrial myocardium were down-regulated in atrial fibrillation (e.g. signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium, uncovering the transcriptional response pattern in pmAF (Barth AS et al., Circ Res, 2005).

请注意本数据集包含两份完全一致的数据文件：GSM40994.txt与GSM40995.txt。GSE2240包含两个独立的实验子数据集：
1) 心房与心室基因表达比较（窦性心律患者心房组织 vs 人类左心室非衰竭心肌组织）
本研究旨在阐明人类心房与心室的超微结构和功能特化的转录调控基础。我们通过探索性微阵列分析（Affymetrix U133A+B芯片），在人类心脏组织中检测到11740个表达的转录本，为迄今为止最全面的人类心肌转录组研究报道。心房与心室之间的基因表达差异为本数据集的最大差异来源：分别有3300和2974个转录本在心房和心室中呈高表达。基于基因本体论（Gene Ontology）的功能分类揭示了心房与心室的基因表达模式差异，并为心肌细胞的区域特化提供了分子层面的见解，将重要的功能通路与转录活性相关联：心室肌细胞优先表达满足收缩功能与能量代谢需求的基因，而心房肌细胞则表现出与神经体液调节功能相关的特异性转录活性。此外，多个促纤维化与凋亡通路在心房心肌组织中富集，这印证了在人类及心力衰竭实验动物模型中观察到的心房更易发生程序性细胞死亡与细胞外基质重塑的现象。因此，心房与心室的转录谱差异为心肌细胞多样性以及区域特异性适应生理和病理生理状态的分子机制提供了新的见解（Barth AS等，《欧洲生理学杂志》，2005年）。
2) 永久性心房颤动（permanent atrial fibrillation，以下简称pmAF）患者与窦性心律患者的心房基因表达比较
心房颤动与心房心肌组织中心室肌肌球蛋白亚型的表达上调相关，这一过程被认为是细胞去分化过程的一部分。目前尚不明确心房颤动时心室肌亚型的重新表达是否仅局限于编码收缩蛋白的转录本。因此，本研究采用Affymetrix U133芯片，比较了永久性心房颤动患者、窦性心律患者的心房mRNA表达，以及心室基因表达谱。在心房心肌组织中，我们鉴定出1434个在心房颤动中存在表达失调的基因，其中大多数（包括钙依赖信号通路的关键调控元件）呈现表达下调。基于基因本体论的功能分类明确了结构重塑、收缩重塑与电生理重塑这三个相互关联的过程的特异性基因集。此外，我们首次证实了代谢活性相关转录本的显著上调，这提示颤动状态的心房心肌组织存在对代谢需求增加的适应性反应。心室优势基因在心房颤动中上调的概率是心房特异性转录本的5倍（174个基因上调，35个基因下调），而心房特异性转录本则主要呈现下调（56个基因上调，564个基因下调）。总体而言，在心房颤动的心房心肌组织中，特征性的心室肌功能基因类别呈现上调（例如代谢过程），而心房肌特异性的功能基因类别则呈现下调（例如信号转导与细胞通讯）。因此，获得心室样基因表达特征的细胞去分化过程是颤动心房的普遍特征，揭示了永久性心房颤动（pmAF）中的转录应答模式（Barth AS等，《循环研究》，2005年）。