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J Am Coll Cardiol, 2003; 42:271-277, doi:10.1016/S0735-1097(03)00626-0
© 2003 by the American College of Cardiology Foundation
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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{dagger}, Norman B. Ratliff, MD{ddagger}, Delos M. Cosgrove, III, MD§ and Ivan Vesely, PhD*,*

* Biomedical Engineering, The Cleveland Clinic Foundation,, Cleveland, Ohio USA
{dagger} Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio USA
{ddagger} 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.

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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