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MMP9 variation after thrombolysis is associated with hemorrhagic transformation of lesion and death

Domenico Inzitari1, Betti Giusti, Patrizia Nencini

  • 1From the Stroke and Neurology Unit, Careggi University Hospital, Florence, Italy (D.I., P.N., M.N., V.P., B.P., G.P.); Department of Experimental and Clinical Medicine, Thrombosis Centre, University of Florence, Florence, Italy (B.G., A.M.G., A.A., R.A.); Neurology Unit, Ospedale di Circolo e Fondazione Macchi, University of Insubria, Varese, Italy (G.B.); SSO Stroke Unit, U.O. Neurologia d.O., DAI di Neuroscienze, Azienda Ospedaliera Integrata, Verona, Italy (P.B.); U.O. Neurologia, G. Jazzolino Hospital, Vibo Valentia, Italy (D.C.); Neurology Unit, Valduce General Hospital, Como, Italy (M.G.); Neurology Unit, Arcispedale Santa Maria Nuova, Reggio Emilia, Italy (A.N.); Neurology Unit, Misericordia e Dolce Hospital, Prato, Italy (F.M.); Istituto Neurologico Nazionale C. Mondino, Pavia, Italy (G.M.); Department of Neurosciences, Neurological Clinic, University of Pisa, Pisa, Italy (G.O.); UOC di Neurologia e "Stroke Unit", Ospedale San Bortolo, Vicenza, Italy (F.P.); U.O.C. Stroke Unit, Dipartimento di Scienze Neurologiche e Neurosensoriali, Azienda Ospedaliera Universitaria Senese, Siena, Italy (R.T.); UO Neurologia, DAI Neuroscienze-Riabilitazione, Azienda Ospedaliera-Universitaria S. Anna, Ferrara, Italy (M.R.T.); Department of Neurology, San Raffaele Scientific Institute, Milan, Italy (M.S.); and Emergency Department Stroke Unit and Department of Neurological Sciences, Sapienza University of Rome, Rome, Italy (D.T.).

Stroke
|August 3, 2013
PubMed
Abstract

Insights

Matrix metalloproteinase-9 (MMP-9) levels predict poor outcomes in ischemic stroke patients treated with tissue-type plasminogen activator (tPA). Elevated MMP-9 is linked to increased risk of death and hemorrhagic transformation, suggesting therapeutic targets.

Area of Science:

  • Biochemistry and Molecular Biology
  • Neurology and Neuroscience
  • Cardiovascular and Hematologic Disorders

Background:

  • Matrix metalloproteinases (MMPs) are implicated in the pathophysiology of ischemic stroke.
  • Experimental studies suggest MMPs exacerbate hemorrhagic transformation and lesion severity.
  • Tissue-type plasminogen activator (tPA) treatment for ischemic stroke may influence MMP activity.

Purpose of the Study:

  • To investigate the clinical association between circulating MMP levels and outcomes in acute ischemic stroke patients receiving tPA.
  • To determine if MMP variations correlate with symptomatic intracerebral hemorrhage, mortality, or functional disability.

Main Methods:

  • Blood samples were collected from 327 acute ischemic stroke patients before and 24 hours after tPA administration.
  • Circulating levels of MMPs (1, 2, 3, 7, 8, 9) and tissue inhibitors of metalloproteinases (TIMPs 1, 2, 4) were measured.
  • Changes in MMP and TIMP levels were analyzed in relation to symptomatic intracerebral hemorrhage, 3-month death, and modified Rankin Scale scores.

Main Results:

  • Matrix metalloproteinase-9 (MMP-9) variation was independently associated with an increased risk of death (OR 1.58) and symptomatic intracerebral hemorrhage (OR 1.40).
  • Both MMP-9 and tissue inhibitor of metalloproteinase-4 (TIMP-4) changes correlated with National Institutes of Health Stroke Scale scores at baseline, 24 hours, and 7 days.
  • No significant associations were found for other MMPs or TIMPs with the studied clinical outcomes.

Conclusions:

  • Clinical evidence supports a detrimental role for MMP-9 in ischemic stroke patients treated with thrombolysis.
  • MMP-9 may serve as a predictive biomarker for adverse outcomes following tPA therapy.
  • Targeting MMP-9 activity warrants investigation in future clinical trials for ischemic stroke.
Keywords:
acute strokemetalloproteinasesthrombolytic therapytreatment outcome

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