CLINICAL RESEARCH: MITRAL PROLAPSE SYNDROME
Glycosaminoglycan profiles of myxomatous mitral leaflets and chordae parallel the severity of mechanical alterations
K. Jane Grande-Allen, PhD*,
Brian P. Griffin, MD, FACC ,
Norman B. Ratliff, MD ,
Delos M. Cosgrove, III, MD and
Ivan Vesely, PhD*,*
* Biomedical Engineering, The Cleveland Clinic Foundation,, Cleveland, Ohio USA
Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio USA
Anatomic Pathology, The Cleveland Clinic Foundation, Cleveland, Ohio USA
Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, Cleveland, Ohio, USA
Manuscript received December 11, 2002;
revised manuscript received March 17, 2003,
accepted April 17, 2003.
* Reprint requests and correspondence: Dr. Ivan Vesely, Department of Biomedical Engineering/ND20, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
vesely{at}bme.ri.ccf.org
OBJECTIVES: This biochemical study compared the extracellular matrix of normal mitral valves and myxomatous mitral valves with either unileaflet prolapse (ULP) or bileaflet prolapse (BLP).
BACKGROUND: Myxomatous mitral valves are weaker and more extensible than normal valves, and myxomatous chordae are more mechanically compromised than leaflets. Despite histological evidence that glycosaminoglycans (GAGs) accumulate in myxomatous valves, previous biochemical analyses have not adequately examined the different GAG classes.
METHODS: Leaflets and chordae from myxomatous valves (n = 41 ULP, 31 BLP) and normal valves (n = 27) were dried, dissolved, and assayed for deoxyribonucleic acid, collagen, and total GAGs. Specific GAG classes were analyzed with selective enzyme digestions and fluorophore-assisted carbohydrate electrophoresis.
RESULTS: Biochemical changes were more pronounced in chordae than in leaflets. Myxomatous leaflets and chordae had 3% to 9% more water content and 30% to 150% higher GAG concentrations than normal. Collagen concentration was slightly elevated in the myxomatous valves. Chordae from ULP had 62% more GAGs than those from BLP, primarily from elevated levels of hyaluronan and chondroitin-6-sulfate.
CONCLUSIONS: The GAG classes elevated in the myxomatous chordae are associated with matrix microstructure and elastic fiber deficiencies and may influence the hydration-related "floppy" nature of these tissues. These abnormalities may be related to the reported mechanical weakness of myxomatous chordae. The biochemical differences between ULP and BLP confirm previous mechanical and echocardiographic distinctions.
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Abbreviations and Acronyms
| | ACII | | chondroitinase ACII | | BLP | | bileaflet prolapse | | CS | | chondroitin sulfate | | DNA | | deoxyribonucleic acid | | DS | | dermatan sulfate | | FACE | | fluorophore-assisted carbohydrate electrophoresis | | GAG | | glycosaminoglycan | | HA | | hyaluronan | | HABC | | hyaluronidase SD (Streptococcus dysgalactiae) plus chondroitinase ABC | | ULP | | unileaflet prolapse |
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