Serial gene expression profiling in the intact human heart
Serial gene expression profiling in the intact human heart
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DOI：
10.1016/j.healun.2006.01.006
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发表时间：
2006-05-01
影响因子：
8.9
通讯作者：
Bristow, MR
中科院分区：
文献类型：
--
作者：
Lowes, BD;Zolty, R;Bristow, MR
背景：在扩张型心肌病表型引起的慢性心力衰竭中，收缩功能障碍和心室重塑的分子基础在很大程度上仍未确定。方法：为了研究连续测量完整衰竭人类心脏整体基因表达的可行性，我们使用从8例特发性扩张型心肌病患者的心内膜活检标本中提取的RNA和基因芯片方法进行了重复信使RNA （mRNA）表达谱分析。在接受β -阻滞剂或安慰剂治疗的患者中，在基线和治疗4至12个月后测量心肌内膜活检材料中的心肌基因表达和放射性核素射血分数。采用Affymetrix U95基因芯片和市售软件检测12625个基因序列的基因表达。对6个mrna，将基因芯片结果与定量逆转录聚合酶链反应（RT-PCR）测定结果进行比较。结果：在对高信号强度芯片患者检测到的表达变化进行未经过滤的综合分析中，241个基因的mRNA丰度增加，331个基因的mRNA丰度减少。定量RT-PCR测定的变化与基因芯片测定的变化有很好的一致性。与在基线取样时具有相似表型的受试者相比，连续取样患者的表型差异之间的差异较小。结论：与表型变化相关的序列基因表达谱在完整的人类心脏中是可行的，并且可能具有横断面表达谱的优势。这项研究表明，完整的衰竭重塑人类心脏处于基因表达的激活状态，随着表型改善的发生，基因表达的净大幅减少。
Background: In chronic heart failure due to a dilated cardiomyopathy phenotype, the molecular bases for contractile dysfunction and chamber remodeling remain largely unidentified.Methods: To investigate the feasibility of measuring global gene expression serially in the intact failing human heart, we performed repeated messenger RNA (mRNA) expression profiling using RNA extracted from endomyocardial biopsy specimens and gene chip methodology in 8 subjects with idiopathic dilated cardiomyopathy. In patients treated with beta-blocking agents or placebo, myocardial gene expression was measured in endomyocardial biopsy material and radionuclide ejection fraction was measured at baseline and after 4 to 12 months of treatment. Gene expression was measured for 12,625 gene sequences by using Affymetrix U95 gene chips and commercially available software. For 6 mRNAs, gene chip results were compared with measurements made by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).Results: In an unfiltered composite analysis of changes in expression detected in the patients with high-signal intensity chips, 241 genes showed an increase and 331 genes a decrease in mRNA abundance. There was good agreement between changes measured by quantitative RT-PCR and those determined by gene chips. There was less variance between differences in phenotype in patients sampled serially as compared between subjects with similar phenotypes sampled at baseline.Conclusions: Serial gene expression profiling with association to phenotypic change is feasible in the intact human heart and may offer advantages to cross-sectional expression profiling. This study suggests that the intact failing remodeled human heart is in an activated state of gene expression, with a large net reduction in gene expression occurring as phenotypic improvement occurs.