title: Abundance and location of proteoglycans and hyaluronan within normal and myxomatous mitral valves.
abstract: BACKGROUND
  Extracellular matrix changes occur in many heart valve pathologies. For example, myxomatous mitral valves are reported to contain excess proteoglycans and hyaluronan. However, it is unknown which specific proteoglycans are altered in myxomatous valves. Because proteoglycans perform varied functions in connective tissues, this study was designed to identify and localize three matrix-associated proteoglycans, as well as hyaluronan and the hyaluronan receptor for endocytosis, within myxomatous and normal mitral valves.
  
  
  METHODS
  Human mitral posterior leaflets (control, n=6-9; myxomatous, n=14-21; mean age, 61 years for all groups) were histochemically stained for proteoglycan core proteins, hyaluronan, and the hyaluronan receptor for endocytosis. Stain intensity was semiquantitatively graded to determine differences in marker abundance between normal and myxomatous valves. The proteoglycans were localized to different regions of the leaflet by correspondence to parallel Movat-stained sections.
  
  
  RESULTS
  The proteoglycans decorin, biglycan, and versican were more abundant in myxomatous valves than in normal controls (P<.03). There was a gender effect on proteoglycan presence, but no age-related trends were observed. Hyaluronan and the hyaluronan receptor for endocytosis were distributed throughout all valves. There was no significant difference in hyaluronan between groups, but expression of the hyaluronan receptor for endocytosis was reduced in myxomatous valves compared to normal controls (P<.002).
  
  
  CONCLUSIONS
  Excess decorin, biglycan, and versican may be associated with the remodeling of other matrix components in myxomatous mitral valves. Decreased expression of the hyaluronan receptor for endocytosis in myxomatous valves suggests that hyaluronan metabolism could be altered in myxomatous mitral valve disease. These findings contribute towards elucidating the pathogenesis of myxomatous mitral valve disease and developing potential new therapies.
authors.affiliation: Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX 77251, USA.
authors.forename: Vishal
authors.initials: V
authors.lastname: Gupta
authors.forename: Janet E
authors.initials: JE
authors.lastname: Barzilla
authors.forename: Joe S
authors.initials: JS
authors.lastname: Mendez
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Stephens
authors.forename: Elaine L
authors.initials: EL
authors.lastname: Lee
authors.forename: C David
authors.initials: CD
authors.lastname: Collard
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Laucirica
authors.forename: Paul H
authors.initials: PH
authors.lastname: Weigel
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Grande-Allen
mesh_terms: D000367:Age Factors; D000368:Aged; D058578:Biglycan; D015816:Cell Adhesion Molecules, Neuronal / Q000032:analysis; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D008943:Mitral Valve / Q000737:chemistry* / Q000473:pathology; D008944:Mitral Valve Insufficiency / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000032:analysis*; D012737:Sex Factors; D053675:Versicans / Q000032:analysis
chemical_list: C546884:BGN protein, human; D058578:Biglycan; D015816:Cell Adhesion Molecules, Neuronal; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; C449927:STAB2 protein, human; C508322:VCAN protein, human; D053675:Versicans; D006820:Hyaluronic Acid