title: Hypoplastic left heart syndrome myocytes are differentiated but possess a unique phenotype.
abstract: BACKGROUND
  Hypoplastic left heart syndrome (HLHS) is the term used to describe a group of congenital malformations characterized by marked underdevelopment of the left side of the heart. HLHS accounts for nearly 25% of cardiac deaths in the first year of life. Although much has been reported regarding diagnosis, gross morphology and surgical treatment, no information on gene expression in HLHS myocytes is available.
  
  
  METHODS
  We examined heart tissue from patients with HLHS using routine histology, immunohistochemistry, quantitative polymerase chain reaction (PCR), two-dimensional (2-D) gel electrophoresis and protein identification by mass spectrometry.
  
  
  RESULTS
  Histologic examination of right and left ventricles from HLHS patients revealed characteristic features of myocyte differentiation, including striations and intercalated disc formation. Immunohistochemical staining using antibody to N-cadherin demonstrated clear development of intercalated discs between myocytes. However, many of the myocytes contained scant cytoplasm and were grouped in small, disorganized bundles separated by abundant connective tissue and dilated, thin-walled vessels. Quantitative PCR analysis demonstrated that both left and right ventricular tissue from HLHS hearts expressed the fetal or "heart failure" gene expression pattern. Two-dimensional gel electrophoresis and protein identification by mass spectrometry also confirmed that myocytes from HLHS ventricles were differentiated but expressed the fetal isoform of some cardiac specific proteins. However, HLHS myocytes in all of the heart samples (n=21) were inappropriately expressing platelet-endothelial cell adhesion molecule-1 (PECAM-1, CD31), a member of the cell adhesion molecule (CAM) family that has a primary role in the regulation of tissue morphogenesis. These findings indicate that myocytes from HLHS syndrome patients, while differentiated, have a unique gene expression pattern.
authors.affiliation: Department of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, Denver, CO 80246, USA.
authors.forename: Teresa J
authors.initials: TJ
authors.lastname: Bohlmeyer
authors.forename: Steve
authors.initials: S
authors.lastname: Helmke
authors.forename: Shuping
authors.initials: S
authors.lastname: Ge
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lynch
authors.forename: Gary
authors.initials: G
authors.lastname: Brodsky
authors.forename: James H
authors.initials: JH
authors.lastname: Sederberg
authors.forename: Alastair D
authors.initials: AD
authors.lastname: Robertson
authors.forename: Wayne
authors.initials: W
authors.lastname: Minobe
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bristow
authors.forename: M Benjamin
authors.initials: MB
authors.lastname: Perryman
mesh_terms: D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis; D002454:Cell Differentiation / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D013058:Mass Spectrometry; D032383:Myocytes, Cardiac / Q000473:pathology / Q000502:physiology*; D010641:Phenotype; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D015820:Cadherins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger