Faculty Collaboration Database

Myocardial alternative RNA splicing and gene expression profiling in early stage hypoplastic left heart syndrome. PLoS One 2012;7(1):e29784

Date

02/03/2012

Pubmed ID

22299024

Pubmed Central ID

PMC3267718

DOI

10.1371/journal.pone.0029784

Scopus ID

2-s2.0-84863048063 (requires institutional sign-in at Scopus site)   24 Citations

Abstract

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.

Author List

Ricci M, Xu Y, Hammond HL, Willoughby DA, Nathanson L, Rodriguez MM, Vatta M, Lipshultz SE, Lincoln J

Author

Joy Lincoln PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Alternative Splicing
Case-Control Studies
Cluster Analysis
Female
Gene Expression Profiling
Gestational Age
Humans
Hypoplastic Left Heart Syndrome
Infant, Newborn
Male
Microarray Analysis
Myocardium
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Validation Studies as Topic