New Evidence for a Critical Role of Elastin in Calcification of Native Heart Valves: Immunohistochemical and Ultrastructural Study With Literature Review

Histopathology. 2011 Sep;59(3):504-13. doi: 10.1111/j.1365-2559.2011.03977.x.

Abstract

Aims: Calcific aortic stenosis is a progressive disease characterized by massive fibrosis andmineralization of the valve leaflets. The aim of this study was to determine whether the onset of native calcific aortic stenosis is associated primarily with matrix remodelling events, and particularly with elastin degradation.

Methods and results: The immunohistochemical expression profile of matrix degradating enzymes and tenascin-C was investigated in both healthy and native calcified aortic valves. Collagen and elastic tissue were studied by light microscopy and electron microscopy. Immunophenotypic analysis of inflammatory cells was carried out by using monoclonal antibodies to macrophages, T and B lymphocytes. Immunoreactivity for tenascin-C and matrix metalloproteinase-12 (MMP-12) was associated with areas of dense mineralization, which were characterized by fibrosis, fragmentation and calcification of elastic fibres a positive reaction was also found around small islands of calcification. MMP-11 was not detected in the diseased valves. Osteopontin and osteonectin were also found at sites of mineralization. All calcified valves examined showed inflammatory cell infiltration.

Conclusions: Our results demonstrate the direct involvement of MMP-12 in native aortic valve stenosis. MMP-mediated degradation of elastic fibres might contribute actively to valve mineralization by inducing calcium deposition onto fragmented elastin.

Publication types

  • Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aortic Valve / metabolism
  • Aortic Valve / ultrastructure
  • Aortic Valve Stenosis / immunology
  • Aortic Valve Stenosis / metabolism*
  • Aortic Valve Stenosis / pathology
  • Calcinosis / immunology
  • Calcinosis / metabolism*
  • Calcinosis / pathology
  • Elastin / metabolism*
  • Female
  • Humans
  • Immunohistochemistry
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Matrix Metalloproteinase 12 / metabolism
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Osteonectin / metabolism
  • Osteopontin / metabolism
  • Tenascin / metabolism

Substances

  • Osteonectin
  • Tenascin
  • Osteopontin
  • Elastin
  • Matrix Metalloproteinase 12