title: TIMP-1 resistant matrix metalloproteinase-9 is the predominant serum active isoform associated with MRI activity in patients with multiple sclerosis.
abstract: BACKGROUND
  The activity of matrix metalloproteinase-9 (MMP-9) depends on two isoforms, an 82 kDa active MMP-9 modulated by its specific tissue inhibitor (TIMP-1), and a 65 kDa TIMP-1 resistant active MMP-9. The relevance of these two enzymatic isoforms in multiple sclerosis (MS) is still unknown.
  
  
  OBJECTIVE
  To investigate the contribution of the TIMP-1 modulated and resistant active MMP-9 isoforms to MS pathogenesis.
  
  
  METHODS
  We measured the serum levels of the 82 kDa and TIMP-1 resistant active MMP-9 isoforms by activity assay systems in 86 relapsing-remitting MS (RRMS) patients, categorized according to clinical and magnetic resonance imaging (MRI) evidence of disease activity, and in 70 inflammatory (OIND) and 69 non-inflammatory (NIND) controls.
  
  
  RESULTS
  Serum levels of TIMP-1 resistant MMP-9 were more elevated in MS patients than in OIND and NIND (p < 0.05, p < 0.02, respectively). Conversely, 82 kDa active MMP-9 was higher in NIND than in the OIND and MS patients (p < 0.01 and p < 0.00001, respectively). MRI-active patients had higher levels of TIMP-1 resistant MMP-9 and 82 kDa active MMP-9, than did those with MRI inactive MS (p < 0.01 and p < 0.05, respectively).
  
  
  CONCLUSIONS
  Our findings suggested that the TIMP-1 resistant MMP-9 seem to be the predominantly active isoform contributing to MS disease activity.
authors: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Italy.
authors: Alessandro
authors: A
authors: Trentini
authors: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Italy.
authors: Maria C
authors: MC
authors: Manfrinato
authors: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Italy.
authors: Massimiliano
authors: M
authors: Castellazzi
authors: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Italy.
authors: Carmine
authors: C
authors: Tamborino
authors: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Italy.
authors: Gloria
authors: G
authors: Roversi
authors: Department of Morphology, Surgery and Experimental Medicine; University of Ferrara; Italy.
authors: Carlo A
authors: CA
authors: Volta
authors: Department of Neurosciences and Rehabilitation, Azienda Ospedaliera-Universitaria, Arcispedale S Anna, Ferrara, Italy.
authors: Eleonora
authors: E
authors: Baldi
authors: Department of Neuroscience, Azienda Ospedaliera Universitaria, Arcispedale S Anna, Ferrara, Italy.
authors: Maria R
authors: MR
authors: Tola
authors: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Italy.
authors: Enrico
authors: E
authors: Granieri
authors: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Italy.
authors: Franco
authors: F
authors: Dallocchio
authors: Department of Biomedical and Specialist Surgical Sciences, University of Ferrara, Italy.
authors: Tiziana
authors: T
authors: Bellini
authors: Department of Neuroscience, Azienda Ospedaliera Universitaria, Arcispedale S Anna, Ferrara, Italy henryfai@tin.it.
authors: Enrico
authors: E
authors: Fainardi
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000201:enzymology* / Q000473:pathology*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D007527:Isoenzymes; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Biomarkers; TIMP-1 resistance; enzymes; inflammation; isoforms; magnetic resonance imaging; matrix metalloproteinase 9; multiple sclerosis; serum levels