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Circulating TIMP-1 is associated with hematoma volume in patients with spontaneous intracranial hemorrhage

Manuel Navarro-Oviedo1, Roberto Muñoz-Arrondo2, Beatriz Zandio2

  • 1Laboratory of Atherothrombosis, CIMA, Universidad de Navarra, Instituto de Investigación Sanitaria de Navarra, IdisNA, Pamplona, Spain.

Scientific Reports
|June 27, 2020
PubMed

Insights

Tissue inhibitors of matrix metalloproteinases (TIMPs) show potential as biomarkers for intracranial hemorrhage (ICH). TIMP-1 levels correlate with hematoma volume, and its administration may offer therapeutic benefits in ICH cases.

Area of Science:

  • Biochemistry
  • Neuroscience
  • Clinical Medicine

Background:

  • Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play roles in tissue remodeling and are implicated in various pathologies.
  • Intracranial hemorrhage (ICH) is a critical condition with significant morbidity and mortality, necessitating improved diagnostic and therapeutic tools.

Purpose of the Study:

  • To investigate the potential of MMPs and TIMPs as clinical biomarkers for spontaneous non-traumatic ICH.
  • To explore the relationship between plasma levels of specific MMPs and TIMP-1 with clinical, radiological, and functional outcomes in ICH patients.
  • To evaluate the effect of TIMP-1 administration on bleeding in an experimental model.

Main Methods:

  • Recruitment of 29 patients from Complejo Hospitalario de Navarra (CHN) and 76 from Vall d´Hebron (VdH) with spontaneous non-traumatic ICH.
  • Measurement of plasma levels of MMP-1, -2, -7, -9, -10, and TIMP-1.
  • Correlation analysis between biomarker levels and clinical, radiological (hematoma volume), and functional variables.
  • Experimental study of TIMP-1 (0.05-0.2 mg/Kg) in a mouse tail-bleeding model.

Main Results:

  • In CHN, TIMP-1 correlated with admission-hematoma volume, and MMP-7 was higher in deep ICH compared to lobar ICH.
  • In VdH, admission-hematoma volume was associated with TIMP-1 and MMP-7.
  • Combined analysis showed a significant association between TIMP-1 levels and hematoma volume (β = 0.14, p < 0.05).
  • Mice treated with TIMP-1 (0.2 mg/Kg) exhibited significantly reduced bleeding times (p < 0.01).

Conclusions:

  • The consistent association of TIMP-1 with hematoma volume in two independent ICH cohorts highlights its potential as a valuable biomarker for ICH.
  • Elevated TIMP-1 may not fully counteract MMP upregulation in ICH, suggesting that TIMP-1 administration could be a promising therapeutic strategy to mitigate bleeding.

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