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Glycobiology Advance Access published online on March 24, 2004
Glycobiology, doi:10.1093/glycob/cwh076
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Submitted on December 1, 2003
Revised on March 2, 2004
Accepted on March 5, 2004

© 2004 Glycobiology © Oxford University Press 2004; all rights reserved.

ORIGINAL ARTICLES

Glycosaminoglycans and proteoglycans in normal mitral valve leaflets and chordae: association with regions of tensile and compressive loading

K. Jane Grande-Allen 1*, Anthony Calabro 2, Vishal Gupta 1, Thomas N. Wight 3, Vincent C. Hascall 2, and Ivan Vesely 2

1 Department of Bioengineering, Rice University, Houston, TX, 77005, USA
2 Department of Biomedical Engineering, Lerner Research Institute The Cleveland Clinic Foundation, Cleveland, Ohio, 44195, USA
3 Department of Vascular Biology, Hope Heart Institute, Seattle, WA, 98104, USA

* To whom correspondence should be addressed. E-mail: grande{at}rice.edu.

Abstract

This study was designed to identify the specific proteoglycans and glycosaminoglycans (GAGs) in the leaflets and chordae of the mitral valve, and to interpret their presence in relation to the tensile and compressive loads borne by these tissues. Leaflets and chordae from normal human mitral valves (n = 31, obtained at autopsy) were weighed and selected portions digested using Proteinase K, hyaluronidase, and chondroitinases. After fluorescent derivatization, fluorophore-assisted carbohydrate electrophoresis was used to separate and quantify the derivatized saccharides specific for each GAG type. In addition, the lengths of the chondroitin/dermatan sulfate chains were determined. Proteoglycans were identified by Western blotting. The regions of the valve that experience tension, such as the chordae and the central portion of the anterior leaflet, contained less water, less hyaluronan, and mainly iduronate and 4-sulfated N-Acetylgalactosamine with chain lengths of 50-70 disaccharides. These GAGs are likely associated with the small proteoglycans decorin and biglycan, which were found in abundance in the tensile regions. The valve regions that experience compression, such as the posterior leaflet and the free edge of the anterior leaflet, contained significantly more water, hyaluronan, and glucuronate and 6-sulfated N-Acetylgalactosamine with chain lengths of 80-90 disaccharides. These GAGs are likely components of water-binding versican aggregates, which were abundant in the compressive loading regions. The relative amounts and distributions of these GAGs are therefore consistent with the tensile and compressive loads that these tissues bear. Finally, the concentrations of total GAGs and many different chondroitin/dermatan sulfate subclasses were significantly decreased with advancing age.


compression, decorin, proteoglycans, tension, versican
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