title: Transcription repression and blocks in cell cycle progression in hypoplastic left heart syndrome.
abstract: Hypoplastic left heart syndrome (HLHS) is characterized by abnormally developed atrial septum and a severe underdevelopment of the left side of the heart. Despite significant advances in its surgical management, little is known about the molecular abnormalities in this syndrome. To gain molecular insights into HLHS, expression profiling by gene-chip microarray (Affymetrix U133 2.0) and by real-time RT-PCR was performed in the atrial septum of patients diagnosed with HLHS and compared with age-matched non-HLHS patients. Hierarchical clustering of all expressed genes with a P < 0.01 of all tissue samples showed two main clusters, one of HLHS and the other of non-HLHS, suggesting different expression patterns by the two groups. Net affix followed by real-time RT-PCR analysis identified the differentially expressed genes to be those involved in chromatin remodeling, cell cycle regulation, and transcriptional regulation. These included remodeling factors, histone deactylase 2 and SET and MYND domain containing 1; transcription factors, FoxP1, and components of the calcineurin-nuclear factor of activated T cells signaling pathway; and cell cycle regulators, cyclin-dependent kinase (CDK)-4, phosphatase and tensin homolog, and p18. Since these factors play essential roles in heart growth and development, the abnormal expression pattern suggests that these molecules may contribute to the pathogenesis of HLHS.
authors.affiliation: The Heart Institute for Children, Hope Children's Hospital, Oak Lawn, IL, USA.
authors.forename: Katheryn
authors.initials: K
authors.lastname: Gambetta
authors.forename: Mohamad K
authors.initials: MK
authors.lastname: Al-Ahdab
authors.forename: Michel N
authors.initials: MN
authors.lastname: Ilbawi
authors.forename: Nahidh
authors.initials: N
authors.lastname: Hassaniya
authors.forename: Madhu
authors.initials: M
authors.lastname: Gupta
mesh_terms: D016022:Case-Control Studies; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics; D042002:Chromatin Assembly and Disassembly; D016000:Cluster Analysis; D003598:Cytoskeletal Proteins / Q000235:genetics; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D006325:Heart Atria / Q000473:pathology; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000235:genetics* / Q000473:pathology; D007231:Infant, Newborn; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D014157:Transcription Factors