title: The rtPA increases MMP-9 activity in serum during ischaemic stroke.
abstract: OBJECTIVE
  To find the relationship between rtPA treatment vs. MMP-9 activity, MMP-3, and TIMP-1 serum levels related to patients' neurological status during acute ischaemic stroke (IS).
  
  
  METHODS
  35 IS patients were enrolled. 14 of them underwent thrombolytic therapy with Actylise (rtPA group). The serum samples were obtained at 3 time-points for rtPA group (time-point 0: 1st-4th hour of stroke; time-point 1 - immediately after rtPA administration; time-point 2 - on day 5-7 from stroke onset). Remaining patients had venous blood collection at two time-points: time-point 1 - 5th-10th hour of stroke and time-point 2 - on day 5-7 of stroke. MMP-9 was analyzed with gelatin zymography, MMP-3 and TIMP-1 serum levels were analyzed with ELISA method. NIHSS improvement ratio (IR) was calculated as a difference between NIHSS score at the admission and discharge of patient.
  
  
  RESULTS
  The active form of MMP-9 (86kDa) was not observed in any analyzed samples. Total MMP-9 activity was significantly elevated at time-point 1 in rtPA group in comparison with non-rtPA group. MMP-3 serum level significantly decreased during rtPA administration in comparison with non-rtPA group and it was restored at time-point 2. MMP-3 negatively correlated with IR values (p=0.06).
  
  
  CONCLUSIONS
  Thrombolysis applied for IS treatment increases MMP-9 activity in serum, however, rtPA does not facilitate the conversion of pro-MMP-9 into the active form. Our results also suggest the involvement of MMP-3 to the biochemical processes occurring during acute phase of IS.
authors.affiliation: Department of Internal Medicine, The Holy Family Specialist Hospital in Rudna Mala, Rzeszów, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Gołąb
authors.affiliation: Department of Medical Chemistry, Medical University of Lublin, Lublin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Boguszewska-Czubara
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of Lublin, Lublin, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Kiełbus
authors.affiliation: Department of Medical Chemistry, Medical University of Lublin, Lublin, Poland. Electronic address: kurzepa@onet.pl.
authors.forename: Jacek
authors.initials: J
authors.lastname: Kurzepa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002545:Brain Ischemia / Q000209:etiology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D009460:Neurologic Examination; D020521:Stroke / Q000097:blood* / Q000150:complications / Q000188:drug therapy*; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D010959:Tissue Plasminogen Activator; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9
keywords: Ischaemic stroke; MMP-3; MMP-9; Matrix metalloproteinases; Thrombolysis