title: Disturbed myocardial connexin 43 and N-cadherin expressions in hypoplastic left heart syndrome and borderline left ventricle.
abstract: OBJECTIVE
  Borderline left ventricle is the left ventricular morphology at the favorable end of the hypoplastic left heart syndrome. In contrast to the severe end, it is suitable for biventricular repair. Wondering whether it is possible to identify cases suitable for biventricular repair from a developmental viewpoint, we investigated the myocardial histology of borderline and severely hypoplastic left ventricles.
  
  
  METHODS
  Postmortem specimens of neonatal, unoperated human hearts with severe hypoplastic left heart syndrome and borderline left ventricle were compared with normal specimens and hearts from patients with transposition of the great arteries. After tissue sampling of the lateral walls of both ventricles, immunohistochemical and immunofluorescence stainings against cardiac troponin I, N-cadherin, and connexin 43, important for proper cardiac differentiation, were done.
  
  
  RESULTS
  All severely hypoplastic left hearts (7/7) and most borderline left ventricle hearts (4/6) showed reduced sarcomeric expressions of troponin I in left and right ventricles. N-cadherin and connexin 43 expressions were reduced in intercalated disks. The remaining borderline left ventricle hearts (2/6) were histologically closer to control hearts.
  
  
  CONCLUSIONS
  Four of 6 borderline left ventricle hearts showed myocardial histopathology similar to the severely hypoplastic left hearts. The remainder were similar to normal hearts. Our results and knowledge regarding the role of epicardial-derived cells in myocardial differentiation lead us to postulate that an abnormal epicardial-myocardial interaction could explain the observed histopathology. Defining the histopathologic severity with preoperative myocardial biopsy samples of hearts with borderline left ventricle might provide a diagnostic tool for preoperative decision making.
authors.affiliation: Department of Anatomy and Embryology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
authors.forename: Edris A F
authors.initials: EA
authors.lastname: Mahtab
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Gittenberger-de Groot
authors.forename: Rebecca
authors.initials: R
authors.lastname: Vicente-Steijn
authors.forename: Heleen
authors.initials: H
authors.lastname: Lie-Venema
authors.forename: Marry E B
authors.initials: ME
authors.lastname: Rijlaarsdam
authors.forename: Mark G
authors.initials: MG
authors.lastname: Hazekamp
authors.forename: Margot M
authors.initials: MM
authors.lastname: Bartelings
mesh_terms: D015703:Antigens, CD / Q000032:analysis*; D001344:Autopsy; D015415:Biomarkers / Q000032:analysis; D015820:Cadherins / Q000032:analysis*; D006348:Cardiac Surgical Procedures; D018031:Connexin 43 / Q000032:analysis*; D015536:Down-Regulation; D005455:Fluorescent Antibody Technique; D006352:Heart Ventricles / Q000002:abnormalities / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D006801:Humans; D018636:Hypoplastic Left Heart Syndrome / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D007150:Immunohistochemistry; D007231:Infant, Newborn; D009206:Myocardium / Q000737:chemistry* / Q000473:pathology; D018579:Patient Selection; D010641:Phenotype; D012189:Retrospective Studies; D012518:Sarcomeres / Q000737:chemistry / Q000473:pathology; D012720:Severity of Illness Index; D014188:Transposition of Great Vessels / Q000378:metabolism / Q000473:pathology; D019210:Troponin I / Q000032:analysis
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; C050361:CDH2 protein, human; D015820:Cadherins; D018031:Connexin 43; C500216:GJA1 protein, human; D019210:Troponin I