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. 1987 Jun 15;244(3):597–603. doi: 10.1042/bj2440597

Biochemical characterization of individual normal, floppy and rheumatic human mitral valves.

Y Lis 1, M C Burleigh 1, D J Parker 1, A H Child 1, J Hogg 1, M J Davies 1
PMCID: PMC1148038  PMID: 3446179

Abstract

Human mitral valves (32 floppy and 17 rheumatic) obtained at surgery were analysed and compared with 35 normal (autopsy) valves. Total amounts of collagen, proteoglycan and elastin were increased approx. 3-fold in floppy and rheumatic valves. The water content of rheumatic cusps was lower than normal. The most significant changes in floppy valves were the 59% increase in mean value of the proteoglycan content, a large increase in the ease of extractability of proteoglycans from 26.7 to 57.2% of the total and a 62% increase in mean value of the elastin content in the anterior cusps. Normal human mitral valve cusps contained a mean proportion of 29.3 (and chordae 26.6) type III collagen (as % of total types III + I collagen), the values increasing significantly to 33.2 and 36.3% respectively in chronic rheumatic disease. The ratio observed in floppy valves depended on the extent of secondary surface fibrosis, which could be demonstrated histologically; in valve cusps with considerable secondary fibrosis, the percentage of type III increased significantly (to 34.4%), whereas it decreased significantly (to 25.2%) when fibrosis was negligible. It is concluded that the ratio of collagen types in floppy valves reflects the extent of secondary fibrosis rather than the pathogenesis of the disrupted collagen in the central core of the valve.

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Selected References

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  1. BITTER T., MUIR H. M. A modified uronic acid carbazole reaction. Anal Biochem. 1962 Oct;4:330–334. doi: 10.1016/0003-2697(62)90095-7. [DOI] [PubMed] [Google Scholar]
  2. Bailey A. J., Lapière C. M. Effect of an additional peptide extension of the N-terminus of collagen from dermatosparactic calves on the cross-linking of the collagen fibres. Eur J Biochem. 1973 Apr 2;34(1):91–96. doi: 10.1111/j.1432-1033.1973.tb02732.x. [DOI] [PubMed] [Google Scholar]
  3. Bailey A. J., Robins S. P., Balian G. Biological significance of the intermolecular crosslinks of collagen. Nature. 1974 Sep 13;251(5471):105–109. doi: 10.1038/251105a0. [DOI] [PubMed] [Google Scholar]
  4. Bailey A. J., Sims T. J. Chemistry of the collagen cross-links. Nature of the cross-links in the polymorphic forms of dermal collagen during development. Biochem J. 1976 Feb 1;153(2):211–215. doi: 10.1042/bj1530211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barlow J. B., Pocock W. A. The problem of nonejection systolic clicks and associated mitral systolic murmurs: emphasis on the billowing mitral leaflet syndrome. Am Heart J. 1975 Nov;90(5):636–655. doi: 10.1016/0002-8703(75)90229-x. [DOI] [PubMed] [Google Scholar]
  6. Bashey R. I., Mori Y., Prosky L. Amino acid composition of bovine heart valve collagen. Proc Soc Exp Biol Med. 1972 Jul;140(3):944–945. doi: 10.3181/00379727-140-36585. [DOI] [PubMed] [Google Scholar]
  7. Bashey R. I., Torii S., Angrist A. Age-related collagen and elastin content of human heart valves. J Gerontol. 1967 Apr;22(2):203–208. doi: 10.1093/geronj/22.2.203. [DOI] [PubMed] [Google Scholar]
  8. Bittar N., Sosa J. A. The billowing mitral valve leaflet. Report on fourteen patients. Circulation. 1968 Oct;38(4):763–770. doi: 10.1161/01.cir.38.4.763. [DOI] [PubMed] [Google Scholar]
  9. Bonella D., Parker D. J., Davies M. J. Accumulation of procollagen in human floppy mitral valves. Lancet. 1980 Apr 19;1(8173):880–881. doi: 10.1016/s0140-6736(80)91382-3. [DOI] [PubMed] [Google Scholar]
  10. Booth B. A., Polak K. L., Uitto J. Collagen biosynthesis by human skin fibroblasts. I. Optimization of the culture conditions for synthesis of type I and type III procollagens. Biochim Biophys Acta. 1980 Mar 28;607(1):145–160. doi: 10.1016/0005-2787(80)90228-2. [DOI] [PubMed] [Google Scholar]
  11. Burleigh M. C., Barrett A. J., Lazarus G. S. Cathepsin B1. A lysosomal enzyme that degrades native collagen. Biochem J. 1974 Feb;137(2):387–398. doi: 10.1042/bj1370387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Byers P. H., McKenney K. H., Lichtenstein J. R., Martin G. R. Preparation of type III procollagen and collagen from rat skin. Biochemistry. 1974 Dec 3;13(25):5243–5248. doi: 10.1021/bi00722a030. [DOI] [PubMed] [Google Scholar]
  13. Caulfield J. B., Page D. L., Kastor J. A., Sanders C. A. Connective tissue abnormalities in spontaneous rupture of chordae tendineae. Arch Pathol. 1971 Jun;91(6):537–541. [PubMed] [Google Scholar]
  14. Cole W. G., Chan D., Hickey A. J., Wilcken D. E. Collagen composition of normal and myxomatous human mitral heart valves. Biochem J. 1984 Apr 15;219(2):451–460. doi: 10.1042/bj2190451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Collins D., Lindberg K., McLees B., Pinnell S. The collagen of heart valve. Biochim Biophys Acta. 1977 Nov 25;495(1):129–139. doi: 10.1016/0005-2795(77)90247-1. [DOI] [PubMed] [Google Scholar]
  16. Criley J. M., Lewis K. B., Humphries J. O., Ross R. S. Prolapse of the mitral valve: clinical and cine-angiocardiographic findings. Br Heart J. 1966 Jul;28(4):488–496. doi: 10.1136/hrt.28.4.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Davies M. J., Moore B. P., Braimbridge M. V. The floppy mitral valve. Study of incidence, pathology, and complications in surgical, necropsy, and forensic material. Br Heart J. 1978 May;40(5):468–481. doi: 10.1136/hrt.40.5.468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Davis R. H., Schuster B., Knoebel S. B., Fisch C. Myxomatous degeneration of the mitral valve. Am J Cardiol. 1971 Oct;28(4):449–455. doi: 10.1016/0002-9149(71)90009-9. [DOI] [PubMed] [Google Scholar]
  19. Devereux R. B., Brown W. T., Kramer-Fox R., Sachs I. Inheritance of mitral valve prolapse: effect of age and sex on gene expression. Ann Intern Med. 1982 Dec;97(6):826–832. doi: 10.7326/0003-4819-97-6-826. [DOI] [PubMed] [Google Scholar]
  20. Fenoglio J. J., Jr, Wagner B. M. Studies in rheumatic fever. VI. Ultrastructure of chronic rheumatic heart disease. Am J Pathol. 1973 Dec;73(3):623–640. [PMC free article] [PubMed] [Google Scholar]
  21. Frable W. J. Mucinous degeneration of the cardiac valves: the "floppy valve" syndrome. J Thorac Cardiovasc Surg. 1969 Jul;58(1):62–70. [PubMed] [Google Scholar]
  22. Gage J. P., Francis M. J., Whitaker G. E., Smith R. Dentine is biochemically abnormal in osteogenesis imperfecta. Clin Sci (Lond) 1986 Apr;70(4):339–346. doi: 10.1042/cs0700339. [DOI] [PubMed] [Google Scholar]
  23. Gravanis M. B., Campbell W. G., Jr The syndrome of prolapse of the mitral valve: an etiologic and pathogenic enigma. Arch Pathol Lab Med. 1982 Aug;106(8):369–374. [PubMed] [Google Scholar]
  24. Guthrie R. B., Edwards J. E. Pathology of the myxomatous mitral value. Nature, secondary changes and complications. Minn Med. 1976 Sep;59(9):637–647. [PubMed] [Google Scholar]
  25. Hammer D., Leier C. V., Baba N., Vasko J. S., Wooley C. F., Pinnell S. R. Altered collagen composition in a prolapsing mitral valve with ruptured chordae tendineae. Am J Med. 1979 Nov;67(5):863–866. doi: 10.1016/0002-9343(79)90746-0. [DOI] [PubMed] [Google Scholar]
  26. Henney A. M., Parker D. J., Davies M. J. Collagen biosynthesis in normal and abnormal human heart valves. Cardiovasc Res. 1982 Nov;16(11):624–630. doi: 10.1093/cvr/16.11.624. [DOI] [PubMed] [Google Scholar]
  27. Hunt D., Sloman G. Prolapse of the posterior leaflet of the mitral valve occurring in eleven members of a family. Am Heart J. 1969 Aug;78(2):149–153. doi: 10.1016/0002-8703(69)90002-7. [DOI] [PubMed] [Google Scholar]
  28. Jaffe A. S., Geltman E. M., Rodey G. E., Uitto J. Mitral valve prolapse: a consistent manifestation of type IV Ehlers-Danlos syndrome. The pathogenetic role of the abnormal production of type III collagen. Circulation. 1981 Jul;64(1):121–125. doi: 10.1161/01.cir.64.1.121. [DOI] [PubMed] [Google Scholar]
  29. Jeresaty R. M. Mitral valve prolapse--Click syndrome. Prog Cardiovasc Dis. 1973 May-Jun;15(6):623–652. doi: 10.1016/s0033-0620(73)80026-x. [DOI] [PubMed] [Google Scholar]
  30. Jimenez S. A., Bashey R. I. Solubilization of bovine heart-value collagen. Biochem J. 1978 Jul 1;173(1):337–340. doi: 10.1042/bj1730337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Kang A. H., Nagai Y., Piez K. A., Gross J. Studies on the structure of collagen utilizing a collagenolytic enzyme from tadpole. Biochemistry. 1966 Feb;5(2):509–515. doi: 10.1021/bi00866a016. [DOI] [PubMed] [Google Scholar]
  32. Kanwar Y. S., Hascall V. C., Farquhar M. G. Partial characterization of newly synthesized proteoglycans isolated from the glomerular basement membrane. J Cell Biol. 1981 Aug;90(2):527–532. doi: 10.1083/jcb.90.2.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Kern W. H., Tucker B. L. Myxoid changes in cardiac valves: pathologic, clinical, and ultrastructural studies. Am Heart J. 1972 Sep;84(3):294–301. doi: 10.1016/0002-8703(72)90361-4. [DOI] [PubMed] [Google Scholar]
  34. King B. D., Clark M. A., Baba N., Kilman J. W., Wooley C. F. "Myxomatous" mitral valves: collagen dissolution as the primary defect. Circulation. 1982 Aug;66(2):288–296. doi: 10.1161/01.cir.66.2.288. [DOI] [PubMed] [Google Scholar]
  35. LANSING A. I., ROBERTS E., RAMASARMA G. B., ROSENTHAL T. B., ALEX M. Changes with age in amino acid composition of arterial elastin. Proc Soc Exp Biol Med. 1951 Apr;76(4):714–717. doi: 10.3181/00379727-76-18604. [DOI] [PubMed] [Google Scholar]
  36. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  37. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  38. Laurent G. J., Cockerill P., McAnulty R. J., Hastings J. R. A simplified method for quantitation of the relative amounts of type I and type III collagen in small tissue samples. Anal Biochem. 1981 May 15;113(2):301–312. doi: 10.1016/0003-2697(81)90081-6. [DOI] [PubMed] [Google Scholar]
  39. Lee Y. S., Lee F. Y., Lu A. H., Chang C. H., Chen H. C., Liang K. F., Chang C. S. Biochemical analysis and electron microscopy of human mitral valve collagen in patients with various etiologies of mitral valve diseases. Jpn Heart J. 1983 Jul;24(4):529–538. doi: 10.1536/ihj.24.529. [DOI] [PubMed] [Google Scholar]
  40. Lichtenstein J. R., Martin G. R., Kohn L. D., Byers P. H., McKusick V. A. Defect in conversion of procollagen to collagen in a form of Ehlers-Danlos syndrome. Science. 1973 Oct 19;182(4109):298–300. doi: 10.1126/science.182.4109.298. [DOI] [PubMed] [Google Scholar]
  41. Light N. D. Estimation of types I and III collagens in whole tissue by quantitation of CNBr peptides on SDS-polyacrylamide gels. Biochim Biophys Acta. 1982 Mar 18;702(1):30–36. doi: 10.1016/0167-4838(82)90024-3. [DOI] [PubMed] [Google Scholar]
  42. Marshall C. E., Shappell S. D. Sudden death and the ballooning posterior leaflet syndrome. Detailed anatomic and histochemical investigation. Arch Pathol. 1974 Aug;98(2):134–138. [PubMed] [Google Scholar]
  43. McCarthy L. J., Wolf P. L. Mucoid degeneration of heart valves: "blue valve syndrome". Am J Clin Pathol. 1970 Dec;54(6):852–856. doi: 10.1093/ajcp/54.6.852. [DOI] [PubMed] [Google Scholar]
  44. Miller D. R., Lust G. Accumulation of procollagen in the degenerative articular cartilage of dogs with osteoarthritis. Biochim Biophys Acta. 1979 Mar 7;583(2):218–231. doi: 10.1016/0304-4165(79)90429-x. [DOI] [PubMed] [Google Scholar]
  45. Moretti A., Whitehouse M. W. Changes in the mucopolysaccharide composition of bovine heart valves with age. Biochem J. 1963 May;87(2):396–402. doi: 10.1042/bj0870396. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Nimni M. E. Collagen: structure, function, and metabolism in normal and fibrotic tissues. Semin Arthritis Rheum. 1983 Aug;13(1):1–86. doi: 10.1016/0049-0172(83)90024-0. [DOI] [PubMed] [Google Scholar]
  47. Nusgens B. V., Goebels Y., Shinkai H., Lapière C. M. Procollagen type III N-terminal endopeptidase in fibroblast culture. Biochem J. 1980 Dec 1;191(3):699–706. doi: 10.1042/bj1910699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Oka M., Girerd R. J., Brodie S. S., Angrist A. Cardiac valve and aortic lesions in beta-aminopropionitrile fed rats with and without high salt. Am J Pathol. 1966 Jan;48(1):45–63. [PMC free article] [PubMed] [Google Scholar]
  49. Pomerance A. Ageing changes in human heart valves. Br Heart J. 1967 Mar;29(2):222–231. doi: 10.1136/hrt.29.2.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Pomerance A. Pathology and valvular heart disease. Br Heart J. 1972 May;34(5):437–443. doi: 10.1136/hrt.34.5.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Pomerance A., Whitney J. C. Heart valve changes common to man and dog: a comparative study. Cardiovasc Res. 1970 Jan;4(1):61–66. doi: 10.1093/cvr/4.1.61. [DOI] [PubMed] [Google Scholar]
  52. Read R. C., Thal A. P., Wendt V. E. Symptomatic valvular myxomatous transformation (the floppy valve syndrome). A possible forme fruste of the Marfan syndrome. Circulation. 1965 Dec;32(6):897–910. doi: 10.1161/01.cir.32.6.897. [DOI] [PubMed] [Google Scholar]
  53. Rentería V. G., Ferrans V. J., Jones M., Roberts W. C. Intracellular collagen fibrils in prolapsed ("floppy") human atrioventricular valves. Lab Invest. 1976 Nov;35(5):439–443. [PubMed] [Google Scholar]
  54. Rippe J., Fishbein M. C., Carabello B., Angoff G., Sloss L., Collins J. J., Jr, Alpert J. S. Primary myxomatous degeneration of cardiac valves. Clinical, pathological, haemodynamic, and echocardiographic profile. Br Heart J. 1980 Dec;44(6):621–629. doi: 10.1136/hrt.44.6.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Ross R. The elastic fiber. J Histochem Cytochem. 1973 Mar;21(3):199–208. doi: 10.1177/21.3.199. [DOI] [PubMed] [Google Scholar]
  56. Schutte J. E., Gaffney F. A., Blend L., Blomqvist C. G. Distinctive anthropometric characteristics of women with mitral valve prolapse. Am J Med. 1981 Oct;71(4):533–538. doi: 10.1016/0002-9343(81)90196-0. [DOI] [PubMed] [Google Scholar]
  57. Shrivastava S., Guthrie R. B., Edwards J. E. Prolapse of the mitral valve. Mod Concepts Cardiovasc Dis. 1977 Dec;46(12):57–61. [PubMed] [Google Scholar]
  58. Strahan N. V., Murphy E. A., Fortuin N. J., Come P. C., Humphries J. O. Inheritance of the mitral valve prolapse syndrome. Discussion of a three-dimensional penetrance model. Am J Med. 1983 Jun;74(6):967–972. doi: 10.1016/0002-9343(83)90791-x. [DOI] [PubMed] [Google Scholar]
  59. Sung Y. T., Lee Y. S., Chang C. H. Altered collagen fibril structure in the spontaneous rupture of chordae tendineae. A brief communication. Taiwan Yi Xue Hui Za Zhi. 1981 Jun;80(6):649–652. [PubMed] [Google Scholar]
  60. Torii S., Bashey R. I., Nakao K. Acid mucopolysaccharide composition of human-heart valve. Biochim Biophys Acta. 1965 Nov 1;101(3):285–291. doi: 10.1016/0926-6534(65)90007-2. [DOI] [PubMed] [Google Scholar]
  61. Trent J. K., Adelman A. G., Wigle E. D., Silver M. D. Morphology of a prolapsed posterior mitral valve leaflet. Am Heart J. 1970 Apr;79(4):539–543. doi: 10.1016/0002-8703(70)90260-7. [DOI] [PubMed] [Google Scholar]
  62. Wagner B. M. Myocardial disease in man and dog, some properties. Ann N Y Acad Sci. 1968 Jul 10;147(8):354–362. doi: 10.1111/j.1749-6632.1968.tb45568.x. [DOI] [PubMed] [Google Scholar]
  63. Weiss A. N., Mimbs J. W., Ludbrook P. A., Sobel B. E. Echocardiographic detection of mitral valve prolapse. Exclusion of false positive diagnosis and determination of inheritance. Circulation. 1975 Dec;52(6):1091–1096. doi: 10.1161/01.cir.52.6.1091. [DOI] [PubMed] [Google Scholar]
  64. Wynne J. Mitral-valve prolapse. N Engl J Med. 1986 Feb 27;314(9):577–578. doi: 10.1056/NEJM198602273140910. [DOI] [PubMed] [Google Scholar]

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