Myocardial alternative RNA splicing and gene expression profiling in early stage hypoplastic left heart syndrome.
Myocardial alternative RNA splicing and gene expression profiling in early stage hypoplastic left heart syndrome.
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DOI：
10.1371/journal.pone.0029784
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Lincoln J
中科院分区：
文献类型：
--
作者：
Ricci M;Xu Y;Hammond HL;Willoughby DA;Nathanson L;Rodriguez MM;Vatta M;Lipshultz SE;Lincoln J
左心发育不良综合征是一种以左心室发育不全和右心室病理性代偿为特征的先天性心脏病。如果不治疗，由于右心室工作负荷的广泛增加和最终的衰竭，HLHS总是致命的。尽管有临床意义，但对HLHS的分子病理生物学状态知之甚少。mRNA转录本的剪接是基因表达的重要调控机制。该过程的组织特异性改变与几种心脏疾病相关，然而，与HLHS相关的转录特征谱尚不清楚。在这项研究中，我们进行了全基因组外显子阵列分析，以确定差异表达的基因和选择性剪接转录在右心室（RV）的6个新生儿与HLHS相比，右心室和左心室（LV）从非疾病对照组。在HLHS中，超过180个基因差异表达，1800个差异剪接，导致各种生物学过程的变化，涉及细胞代谢，细胞骨架和细胞粘附。另外的分层聚类分析显示，与非病变组织相比，HLHS中鉴定的差异基因表达和mRNA剪接模式是独特的。我们的研究结果表明，基因表达和mRNA剪接广泛失调的RV心肌HLHS新生儿。此外，我们的分析确定了代表HLHS分子生物标志物的转录组谱，这些分子生物标志物可用于未来的诊断和预后分层，以改善患者结局。
Hypoplastic Left Heart Syndrome (HLHS) is a congenital defect characterized by underdevelopment of the left ventricle and pathological compensation of the right ventricle. If untreated, HLHS is invariably lethal due to the extensive increase in right ventricular workload and eventual failure. Despite the clinical significance, little is known about the molecular pathobiological state of HLHS. Splicing of mRNA transcripts is an important regulatory mechanism of gene expression. Tissue specific alterations of this process have been associated with several cardiac diseases, however, transcriptional signature profiles related to HLHS are unknown. In this study, we performed genome-wide exon array analysis to determine differentially expressed genes and alternatively spliced transcripts in the right ventricle (RV) of six neonates with HLHS, compared to the RV and left ventricle (LV) from non-diseased control subjects. In HLHS, over 180 genes were differentially expressed and 1800 were differentially spliced, leading to changes in a variety of biological processes involving cell metabolism, cytoskeleton, and cell adherence. Additional hierarchical clustering analysis revealed that differential gene expression and mRNA splicing patterns identified in HLHS are unique compared to non-diseased tissue. Our findings suggest that gene expression and mRNA splicing are broadly dysregulated in the RV myocardium of HLHS neonates. In addition, our analysis identified transcriptome profiles representative of molecular biomarkers of HLHS that could be used in the future for diagnostic and prognostic stratification to improve patient outcome.
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影响因子：
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作者：
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DOI：
10.1073/pnas.0801319105
发表时间：
2008-04-01
影响因子：
11.1
作者：
Einstein, Richard;Jordan, Heather;Liggett, Stephen B.
通讯作者：
Liggett, Stephen B.