Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy
Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy
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DOI：
10.1152/physiolgenomics.00094.2011
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发表时间：
2012-01-01
影响因子：
4.6
通讯作者：
Milting, Hendrik
中科院分区：
文献类型：
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作者：
Gaertner, Anna;Schwientek, Patrick;Milting, Hendrik
[10]杨文，李文.致瘤性右室心肌病的心肌转录组分析。Physiol Genomics 44：99-109，2012.首次发表于2011年11月15日; doi：10.1152/physiolgenomics.00094.2011.-致心律失常性右心室心肌病（ARVC）是一种以心肌细胞纤维脂肪替代为主要特征的右心室遗传性心肌病。ARVC患者的遗传病因最常见的是显性遗传和高度遗传异质性。虽然对受ARVC影响的人类心肌的组织学检查显示了纤维脂肪瘤样替代，但导致心肌细胞损失的分子机制在很大程度上是未知的。因此，我们分析了六个ARVC心脏的转录组，并将我们的发现与六个非衰竭供体心脏（NF）进行了比较。为了表征ARVC特异性转录组，我们将我们的研究结果与7例特发性扩张型心肌病（DCM）患者的样本进行了比较。心肌DCM和ARVC样品从原位心脏移植期间移植的心脏制备，代表来自终末期心力衰竭患者（NYHA IV）的心肌。通过Affytron HG-U133 Plus 2.0阵列分析每颗心脏的左（LV）和右心室（RV）心肌样本，总计6个样本组。无监督的聚类分析显示NF和心肌病样本的明显分离。然而，与其他样品相比，分析显示在心肌ARVC样品的LV和RV中没有明显的表达模式。我们进一步确定差异表达的转录本，使用t检验和发现转录本分离病变和NF心室心肌。值得注意的是，在衰竭心肌中，与NF样本相比，只有15-16%的基因通常受到调控。此外，两种心肌病在转录组水平上明显不同。使用配对t检验比较失败的RV和LV之间的表达模式显示，ARVC心脏中LV和RV基因表达之间缺乏重大差异。我们的研究是第一次分析特定的ARVC相关的RV和LV基因表达模式在终端失败的人类心脏。
Gaertner A, Schwientek P, Ellinghaus P, Summer H, Golz S, Kassner A, Schulz U, Gummert J, Milting H. Myocardial transcriptome analysis of human arrhythmogenic right ventricular cardiomyopathy. Physiol Genomics 44: 99-109, 2012. First published November 15, 2011; doi:10.1152/physiolgenomics.00094.2011.-Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy primarily of the right ventricle characterized through fibrofatty replacement of cardiomyocytes. The genetic etiology in ARVC patients is most commonly caused by dominant inheritance and high genetic heterogeneity. Though histological examinations of ARVC-affected human myocardium reveals fibrolipomatous replacement, the molecular mechanisms leading to loss of cardiomyocytes are largely unknown. We therefore analyzed the transcriptomes of six ARVC hearts and compared our findings to six nonfailing donor hearts (NF). To characterize the ARVC-specific transcriptome, we compared our findings to samples from seven patients with idiopathic dilated cardiomyopathy (DCM). The myocardial DCM and ARVC samples were prepared from hearts explanted during an orthotopic heart transplantation representing myocardium from end-stage heart failure patients (NYHA IV). From each heart, left (LV) and right ventricular (RV) myocardial samples were analyzed by Affymetrix HG-U133 Plus 2.0 arrays, adding up to six sample groups. Unsupervised cluster analyses of the groups revealed a clear separation of NF and cardiomyopathy samples. However, in contrast to the other samples, the analyses revealed no distinct expression pattern in LV and RV of myocardial ARVC samples. We further identified differentially expressed transcripts using t-tests and found transcripts separating diseased and NF ventricular myocardium. Of note, in failing myocardium only similar to 15-16% of the genes are commonly regulated compared with NF samples. In addition both cardiomyopathies are clearly distinct on the transcriptome level. Comparison of the expression patterns between the failing RV and LV using a paired t-test revealed a lack of major differences between LV and RV gene expression in ARVC hearts. Our study is the first analysis of specific ARVC-related RV and LV gene expression patterns in terminal failing human hearts.