title: proMetalloproteinase-10 is associated with brain damage and clinical outcome in acute ischemic stroke.
abstract: BACKGROUND
  Matrix metalloproteinases (MMPs) mediate tissue injury during stroke but also neurovascular remodeling and we have shown that MMP-10 is involved in atherothrombosis.
  
  
  OBJECTIVE
  The purpose of this study was to examine the relationship between proMMP-10 and clinical outcome, assessing inflammatory and proteolytic markers, in patients with acute ischemic stroke.
  
  
  METHODS
  We prospectively studied 76 patients with ischemic stroke treated with tPA within the first 3 h from symptom onset, compared with 202 non-tPA-treated ischemic stroke patients and 83 asymptomatic subjects. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). Hemorrhagic transformation (HT) and severe brain edema were diagnosed by cranial CT. Good functional outcome was defined as a modified Rankin scale score ≤ 2 at 90 days. Serum levels of MMP-9, proMMP-10, TIMP-1, tumor necrosis factor-α (TNFα), interleukin-6 and cellular fibronectin were measured at admission. The effect of TNFα on endothelial proMMP-10 was assessed in vitro.
  
  
  RESULTS
  Serum proMMP-10 concentration in ischemic stroke patients, non-treated or treated with t-PA, which was higher than age-matched healthy subjects (P < 0.0001), was independently associated with higher infarct volume, severe brain edema, neurological deterioration and poor functional outcome at 3 months (all P < 0.05), but not with HT. proMMP-10 levels were also independently and positively associated with circulating levels of TNFα (P < 0.0001), which induced its endothelial expression in vitro, both mRNA and protein. MMP-9, however, was only associated with HT and severe edema (all P < 0.05).
  
  
  CONCLUSIONS
  Increased serum proMMP-10 after acute ischemic stroke, associated with TNFα, is a new marker of brain damage and poor outcome.
authors.affiliation: Laboratory of Atherosclerosis, Division of Cardiovascular Sciences, CIMA-University of Navarra, Pamplona, Spain. josean@unav.es
authors.forename: J A
authors.initials: JA
authors.lastname: Rodríguez
authors.forename: T
authors.initials: T
authors.lastname: Sobrino
authors.forename: J
authors.initials: J
authors.lastname: Orbe
authors.forename: A
authors.initials: A
authors.lastname: Purroy
authors.forename: E
authors.initials: E
authors.lastname: Martínez-Vila
authors.forename: J
authors.initials: J
authors.lastname: Castillo
authors.forename: J A
authors.initials: JA
authors.lastname: Páramo
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002545:Brain Ischemia / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D008297:Male; D053506:Matrix Metalloproteinase 10 / Q000097:blood*; D008875:Middle Aged; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D012720:Severity of Illness Index; D020521:Stroke / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D010959:Tissue Plasminogen Activator; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10
keywords: biological markers; inflammation; matrix metalloproteinases; stroke; tumor necrosis factor-alpha