The rtPA increases MMP-9 activity in serum during ischaemic stroke

Neurol Neurochir Pol. 2014;48(5):309-14. doi: 10.1016/j.pjnns.2014.07.012. Epub 2014 Aug 18.

Abstract

Background and purpose: 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).

Material and 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.

Keywords: Ischaemic stroke; MMP-3; MMP-9; Matrix metalloproteinases; Thrombolysis.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Brain Ischemia / etiology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibrinolytic Agents / therapeutic use*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Male
  • Matrix Metalloproteinase 3 / blood
  • Matrix Metalloproteinase 9 / blood*
  • Neurologic Examination
  • Stroke / blood*
  • Stroke / complications
  • Stroke / drug therapy*
  • Time Factors
  • Tissue Inhibitor of Metalloproteinase-1 / blood
  • Tissue Plasminogen Activator / therapeutic use*

Substances

  • Fibrinolytic Agents
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Plasminogen Activator
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 9