Abundance and location of proteoglycans and hyaluronan within normal and myxomatous mitral valves.
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.
Gupta
Vishal
V
Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX 77251, USA.
Barzilla
Janet E
JE
Mendez
Joe S
JS
Stephens
Elizabeth H
EH
Lee
Elaine L
EL
Collard
C David
CD
Laucirica
Rodolfo
R
Weigel
Paul H
PH
Grande-Allen
Kathryn J
KJ
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
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