title: Extracellular matrix remodelling in human aortic valve disease: the role of matrix metalloproteinases and their tissue inhibitors.
abstract: OBJECTIVE
  Aortic valve diseases are characterized by pathological remodelling of valvular tissue but the cellular and molecular effectors involved in these processes are not well known. The role of matrix metalloproteinase (MMP)-2, MMP-9, MMP-3, MMP-7, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 are investigated here.
  
  
  RESULTS
  Histological analysis of pathological valves [aortic stenosis (AS) (n=49), aortic regurgitation (AR) (n=23)] and control valves (n=8) was performed. The main tissue abnormalities (calcification, inflammatory cells, and capillaries) observed in AS were less severe or absent in AR. However, both groups of pathological valves displayed similar histological signs of extracellular matrix (ECM) remodelling. Biochemical analysis of MMPs and TIMPs (gelatin and casein zymography and ELISA) was performed on valve extracts. MMP-2 activity was not significantly different in control and pathological valves. Increases in MMP-9 and MMP-3 in AS demonstrated an inflammatory state. Finally, there was a four- to seven-fold increase of TIMP-1 in pathological valves. TIMP-1, TIMP-2, and MMP-2 were synthesized by the valvular interstitial cells in primary culture.
  
  
  CONCLUSIONS
  This study demonstrates the involvement of the MMP/TIMP system in ECM remodelling of both AS and AR. These findings provide evidence of inflammatory injury more severe in AS than in AR and involvement of mesenchymal cell response.
authors.affiliation: INSERM U 460, Bâtiment 13, Hôpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75877 Paris Cedex 18, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Fondard
authors.forename: Delphine
authors.initials: D
authors.lastname: Detaint
authors.forename: Bernard
authors.initials: B
authors.lastname: Iung
authors.forename: Christine
authors.initials: C
authors.lastname: Choqueux
authors.forename: Homa
authors.initials: H
authors.lastname: Adle-Biassette
authors.forename: Mohamed
authors.initials: M
authors.lastname: Jarraya
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hvass
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Couetil
authors.forename: Dominique
authors.initials: D
authors.lastname: Henin
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Alec
authors.initials: A
authors.lastname: Vahanian
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Jacob
mesh_terms: D000328:Adult; D001022:Aortic Valve Insufficiency / Q000201:enzymology / Q000473:pathology*; D001024:Aortic Valve Stenosis / Q000201:enzymology / Q000473:pathology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005109:Extracellular Matrix / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases