title: Bicuspid aortic valves with different spatial orientations of the leaflets are distinct etiological entities.
abstract: OBJECTIVE
  The aim of this study was to decide whether bicuspid aortic valves (BAVs) with fused right and noncoronary leaflets (R-N) and BAVs with fused right and left leaflets (R-L) have different etiologies or are the product of a single diathesis.
  
  
  BACKGROUND
  The BAV is the most common congenital cardiac malformation. The R-N and R-L BAVs are the most frequent BAV subtypes.
  
  
  METHODS
  The study was carried out in adult and embryonic hearts of endothelium nitric oxide synthase knock-out mice and inbred Syrian hamsters with a high incidence of R-N and R-L BAVs, respectively. The techniques used were histochemistry, immunohistochemistry, and scanning electron microscopy.
  
  
  RESULTS
  The R-N BAVs result from a defective development of the cardiac outflow tract (OT) endocardial cushions that generates a morphologically anomalous right leaflet. The left leaflet develops normally. The R-L BAVs are the outcome of an extrafusion of the septal and parietal OT ridges that thereby engenders a sole anterior leaflet. The noncoronary leaflet forms normally.
  
  
  CONCLUSIONS
  The R-N and R-L BAVs are different etiological entities. The R-N BAVs are the product of a morphogenetic defect that happens before the OT septation and that probably relies on an exacerbated nitric oxide-dependent epithelial-to-mesenchymal transformation. The R-L BAVs result from the anomalous septation of the proximal portion of the OT, likely caused by a distorted behavior of neural crest cells. Care should be taken in further work on BAV genetics because R-N and R-L BAVs might rely on different genotypes. Detailed screening for R-N and R-L BAVs should be performed for a better understanding of the relationships between these BAV morphologic phenotypes and other heart disease.
authors: Department of Animal Biology, Faculty of Science, University of Málaga, Málaga, Spain. borjafe@uma.es
authors: Borja
authors: B
authors: Fernández
authors: Ana C
authors: AC
authors: Durán
authors: Teresa
authors: T
authors: Fernández-Gallego
authors: M Carmen
authors: MC
authors: Fernández
authors: Miguel
authors: M
authors: Such
authors: Josep M
authors: JM
authors: Arqué
authors: Valentín
authors: V
authors: Sans-Coma
mesh_terms: D000818:Animals; D001021:Aortic Valve / Q000002:abnormalities* / Q000196:embryology; D000013:Congenital Abnormalities / Q000209:etiology; D006224:Cricetinae; D004198:Disease Susceptibility; D051379:Mice; D018345:Mice, Knockout; D008855:Microscopy, Electron, Scanning