Myocardial Alternative RNA Splicing and Gene Expression Profiling in Early Stage Hypoplastic Left Heart Syndrome

• Published in: PloS one Vol. 7; no. 1; p. e29784
• Main Authors: Ricci, Marco, Xu, Yanji, Hammond, Harriet L., Willoughby, David A., Nathanson, Lubov, Rodriguez, Maria M., Vatta, Matteo, Lipshultz, Steven E., Lincoln, Joy
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 27.01.2012; Public Library of Science (PLoS)
• Subjects: Alternative splicing; Alternative Splicing - genetics; Analysis; Arthritis; Bioinformatics; Biological activity; Biology; Biomarkers; Birth defects; Cardiology; Cardiovascular diseases; Case-Control Studies; Cell adhesion; Children & youth; Cluster Analysis; Clustering; Colorectal cancer; Coronary artery disease; Cytoskeleton; Deoxyribonucleic acid; Diagnostic systems; DNA; Female; Gene expression; Gene Expression Profiling; Genes; Genetic disorders; Genetic engineering; Genomes; Genomics; Gestational Age; Heart; Heart diseases; Heart failure; Hospitals; Humans; Hypoplastic left heart syndrome; Hypoplastic Left Heart Syndrome - genetics; Hypoplastic Left Heart Syndrome - metabolism; Hypoplastic Left Heart Syndrome - pathology; Infant, Newborn; Lung cancer; Male; Medical research; Medicine; Messenger RNA; Metabolism; Microarray Analysis; Myocardium; Myocardium - metabolism; Myocardium - pathology; Neonates; Newborn babies; Pediatrics; Phosphorylation; Questioning; Regulatory mechanisms (biology); Reverse Transcriptase Polymerase Chain Reaction; Ribonucleic acid; RNA; RNA, Messenger - metabolism; Skin diseases; Studies; Transcription; Transcription (Genetics); Validation Studies as Topic; Ventricle; Ohio; Florida; United States > US; Texas
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0029784

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.