Gene expression analysis of ischemic and nonischemic cardiomyopathy: shared and distinct genes in the development of heart failure
Gene expression analysis of ischemic and nonischemic cardiomyopathy: shared and distinct genes in the development of heart failure
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DOI：
10.1152/physiolgenomics.00255.2004
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发表时间：
2005-05-11
影响因子：
4.6
通讯作者：
Hare, JM
中科院分区：
文献类型：
--
作者：
Kittleson, MM;Minhas, KM;Hare, JM
心肌病可由多种因素引发，但从独特的激发机制到心室扩张和心输出量减少的共同终点的途径尚不清楚。我们先前描述了一种基于微阵列的预测算法，该算法使用最近的收缩质心区分非缺血性（NICM）和缺血性心肌病（ICM）。因此，我们测试的假设，即NICM和ICM将有共同的和不同的差异表达的基因相对于正常的心脏和比较21 NICM和10 ICM样本的基因表达与6 nonfailing（NF）的心脏使用Affytek U133A基因芯片和微阵列的显著性分析。与NF相比，NICM中有257个基因差异表达，ICM中有72个基因差异表达。两次比较之间只有41个基因共有，主要涉及细胞生长和信号传导。那些在NICM中唯一表达的基因通常参与代谢，而那些在ICM中表达的基因通常具有催化活性。新基因包括血管紧张素转换酶2（ACE2），其在NICM中上调，但在ICM中不上调，这表明ACE2可能在NICM和ICM中提供不同的治疗效果。此外，肿瘤坏死因子受体在NICM和ICM中均下调，表明心力衰竭病理生理学中涉及不同的信号传导途径。这些结果提供了新的见解独特的疾病特异性基因表达之间存在的终末期心肌病的不同病因。该分析表明，转录组分析提供了对心力衰竭管理中基于发病机制的治疗的见解，并补充了使用基于表达的分析来诊断不同病因的心力衰竭的研究。
Cardiomyopathy can be initiated by many factors, but the pathways from unique inciting mechanisms to the common end point of ventricular dilation and reduced cardiac output are unclear. We previously described a microarray-based prediction algorithm differentiating nonischemic (NICM) from ischemic cardiomyopathy (ICM) using nearest shrunken centroids. Accordingly, we tested the hypothesis that NICM and ICM would have both shared and distinct differentially expressed genes relative to normal hearts and compared gene expression of 21 NICM and 10 ICM samples with that of 6 nonfailing (NF) hearts using Affymetrix U133A GeneChips and significance analysis of microarrays. Compared with NF, 257 genes were differentially expressed in NICM and 72 genes in ICM. Only 41 genes were shared between the two comparisons, mainly involved in cell growth and signal transduction. Those uniquely expressed in NICM were frequently involved in metabolism, and those in ICM more often had catalytic activity. Novel genes included angiotensin-converting enzyme-2 (ACE2), which was upregulated in NICM but not ICM, suggesting that ACE2 may offer differential therapeutic efficacy in NICM and ICM. In addition, a tumor necrosis factor receptor was downregulated in both NICM and ICM, demonstrating the different signaling pathways involved in heart failure pathophysiology. These results offer novel insight into unique disease-specific gene expression that exists between end-stage cardiomyopathy of different etiologies. This analysis demonstrates that transcriptome analysis offers insight into pathogenesis-based therapies in heart failure management and complements studies using expression-based profiling to diagnose heart failure of different etiologies.