title: Clear cells in the atrioventricular valves of infants with severe human mucopolysaccharidosis (Hurler syndrome) are activated valvular interstitial cells.
abstract: BACKGROUND
  Severe mucopolysaccharidosis type I (Hurler syndrome) is an autosomal recessive lysosomal storage disease of childhood that results in accumulation of glycosaminoglycans within cardiac valves and consequent valve dysfunction. Valve thickening in mucopolysaccharidosis type I (Hurler syndrome) is due, in part, to the presence of glycosaminoglycan-laden cells (the so-called "clear" or "Hurler" cells) within the valve that remain largely unstudied with respect to identity, origin, and function. We hypothesized that the "clear" or "Hurler" cells within the atrioventricular valves from individuals with untreated mucopolysaccharidosis type I are activated valvular interstitial cells.
  
  
  METHODS
  We performed routine and immunohistochemical staining on atrioventricular valves from two infants with untreated severe mucopolysaccharidosis type I (Hurler syndrome) and compared them to atrioventricular valve tissue from two age-matched and gender-matched normal infants.
  
  
  RESULTS
  Despite the marked differences in their histological appearances, mucopolysaccharidosis type I valve cells have an immunohistochemical fingerprint identical to that of normal infant valvular interstitial cells. Both mucopolysaccharidosis type I valvular interstitial cells and normal infant valvular interstitial cells have the phenotype of activated myofibroblasts, as evidenced by positive staining for vimentin, smooth muscle actin, and metalloproteinase-9. However, the number of mucopolysaccharidosis type I valvular interstitial cells is significantly increased when compared to that of normal cells (P<.0031). Both mucopolysaccharidosis type I (Hurler syndrome) cells and normal valvular interstitial cells express CD34(+), a hematopoietic and capillary endothelial progenitor cell marker, suggesting a common response to activation.
  
  
  CONCLUSIONS
  We conclude that "clear" or "Hurler" cells are valvular interstitial cells with the immunohistochemical phenotype of activated myofibroblasts and may be engaged, albeit ineffectively, in valve repair.
authors.affiliation: Department of Pediatrics, University of Minnesota Hospital/Fairview, Minneapolis, MN 55455, USA. braun002@umn.edu
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Braunlin
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.forename: Shannon
authors.initials: S
authors.lastname: Mackey-Bojack
authors.forename: Tiwanda
authors.initials: T
authors.lastname: Masinde
authors.forename: William
authors.initials: W
authors.lastname: Krivit
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Schoen
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D017809:Fatal Outcome; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D008943:Mitral Valve / Q000473:pathology*; D008059:Mucopolysaccharidosis I / Q000378:metabolism / Q000473:pathology*; D014261:Tricuspid Valve / Q000473:pathology*
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans