title: Relationship between myocardial redox state and matrix metalloproteinase activity in patients on left ventricular assist device support.
abstract: BACKGROUND
  Redox aminothiols have been reported to modulate the activity of recombinant metalloproteinases (MMP). The aim of the present study was to investigate the effects of myocardial redox state on the activities of MMP-2 and -9 implicated in cardiac remodeling in end-stage heart failure patients supported by left ventricular assist device (LVAD).
  
  
  RESULTS
  During heart transplant (HT) surgery, myocardial specimens (MS) from right ventricular walls and LV walls were obtained from 7 LVAD recipients (LVAD group, MS n=35) and from 7 stable HT candidates on medical therapy (MT group, MS n=35). Myocardial MMP-2 and -9 activities and expression, tissue inhibitor of MMP (TIMP)-1 and -4, transforming growth factor (TGF)-β1 and aminothiol concentrations were measured. MMP-2 and -9 activities were evaluated also by incubating MS with different amounts of reduced and oxidized glutathione (GSH). MMP-2 and -9 activities and expression were lower in the LVAD group, whereas myocardial TIMP-1 and -4 concentrations were comparable to those of MT patients. Higher GSH and TGF-β1 concentrations were found in LVAD-recipients. Only GSH concentrations were inversely related to MMP-2 and -9 activities. In vitro, GSH had an inhibitory effect on MMP-2 and -9 activities.
  
  
  CONCLUSIONS
  LVAD recipients show reduced myocardial MMP-2 and -9 activities and expression when compared to medically treated patients. Changes of myocardial redox state, predominantly GSH-dependent, appear to modulate MMP-2 and -9 activities by an inhibitory effect dependent on thiol content. These data support a role of GSH cycle in modulating the extracellular matrix in end-stage heart failure patients supported by LVAD.
authors.affiliation: CNR Clinical Physiology Institute, Cardiovascular Department, Niguarda Cà Granda Hospital Milan, Milan, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Caruso
authors.forename: Chiara
authors.initials: C
authors.lastname: Caselli
authors.forename: Chiara
authors.initials: C
authors.lastname: Boroni
authors.forename: Jonica
authors.initials: J
authors.lastname: Campolo
authors.forename: Filippo
authors.initials: F
authors.lastname: Milazzo
authors.forename: Manuela
authors.initials: M
authors.lastname: Cabiati
authors.forename: Claudio
authors.initials: C
authors.lastname: Russo
authors.forename: Marina
authors.initials: M
authors.lastname: Parolini
authors.forename: Daniela
authors.initials: D
authors.lastname: Giannessi
authors.forename: Maria
authors.initials: M
authors.lastname: Frigerio
authors.forename: Oberdan
authors.initials: O
authors.lastname: Parodi
mesh_terms: D000328:Adult; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006352:Heart Ventricles; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D010084:Oxidation-Reduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000628:therapy*
chemical_list: C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D005978:Glutathione