Molecular changes in fibrillar collagen in myxomatous mitral valve disease

Mojtaba Hadian, Brendan M. Corcoran, Jeremy P. Bradshaw

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Introduction: Myxomatous mitral valve disease (MMVD) is the single most common acquired cardiac disease of dogs and is a disease of significant veterinary importance. It also bears close similarities to mitral valve prolapse in humans and therefore is a disease of emerging comparative interest. We have previously mapped the structure of collagen fibrils in valve leaflets using synchrotron X-rays and have demonstrated changes in collagen structure associated with the regions of disease. Methods: Differential scanning calorimetry (DSC), biochemical assay of collagen content, high-performance liquid chromatography (HPLC), and neutron diffraction were combined with further analysis of our previous X-ray data to elucidate molecular changes in fibrillar collagen in mild to moderately affected MMVD dogs. Results: Comparing diseases and adjacent grossly uninvolved areas in the same leaflets, there was a 20% reduction in collagen fibrils, but only a 10% depletion of collagen content. The enthalpy of collagen denaturation was reduced in affected areas. Chromatography showed a 25% decrease in mature nonreducible covalent cross-links in the affected samples, and neutron diffraction data showed fewer reducible immature covalent cross-links in grossly uninvolved tissue samples. Conclusions: Mild to moderate MMVD in the dog is associated with a marginal decline in collagen content in overtly diseased areas of valves, but more importantly is associated with an increase in immature collagen content. These changes will contribute to the mechanical dysfunction of the leaflet, and this study provides important information on the structure-mechanical alterations associated with this disease. The data suggests MMVD involves a dyscollagenesis process in the development of valve pathology.

Original languageEnglish
Pages (from-to)e141-e148
JournalCardiovascular Pathology
Volume19
Issue number5
DOIs
Publication statusPublished - 1 Sep 2010

Keywords

  • Collagen
  • Differential scanning calorimetry (DSC)
  • Dog
  • High-performance liquid chromatography (HPLC)
  • Myxomatous mitral valve (MMV)
  • Neutron diffraction

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Molecular changes in fibrillar collagen in myxomatous mitral valve disease. / Hadian, Mojtaba; Corcoran, Brendan M.; Bradshaw, Jeremy P.

In: Cardiovascular Pathology, Vol. 19, No. 5, 01.09.2010, p. e141-e148.

Research output: Contribution to journalArticle

Hadian, Mojtaba ; Corcoran, Brendan M. ; Bradshaw, Jeremy P. / Molecular changes in fibrillar collagen in myxomatous mitral valve disease. In: Cardiovascular Pathology. 2010 ; Vol. 19, No. 5. pp. e141-e148.
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abstract = "Introduction: Myxomatous mitral valve disease (MMVD) is the single most common acquired cardiac disease of dogs and is a disease of significant veterinary importance. It also bears close similarities to mitral valve prolapse in humans and therefore is a disease of emerging comparative interest. We have previously mapped the structure of collagen fibrils in valve leaflets using synchrotron X-rays and have demonstrated changes in collagen structure associated with the regions of disease. Methods: Differential scanning calorimetry (DSC), biochemical assay of collagen content, high-performance liquid chromatography (HPLC), and neutron diffraction were combined with further analysis of our previous X-ray data to elucidate molecular changes in fibrillar collagen in mild to moderately affected MMVD dogs. Results: Comparing diseases and adjacent grossly uninvolved areas in the same leaflets, there was a 20{\%} reduction in collagen fibrils, but only a 10{\%} depletion of collagen content. The enthalpy of collagen denaturation was reduced in affected areas. Chromatography showed a 25{\%} decrease in mature nonreducible covalent cross-links in the affected samples, and neutron diffraction data showed fewer reducible immature covalent cross-links in grossly uninvolved tissue samples. Conclusions: Mild to moderate MMVD in the dog is associated with a marginal decline in collagen content in overtly diseased areas of valves, but more importantly is associated with an increase in immature collagen content. These changes will contribute to the mechanical dysfunction of the leaflet, and this study provides important information on the structure-mechanical alterations associated with this disease. The data suggests MMVD involves a dyscollagenesis process in the development of valve pathology.",
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