VAP-1/SSAO plasma activity and brain expression in human hemorrhagic stroke

Cerebrovasc Dis. 2012;33(1):55-63. doi: 10.1159/000333370. Epub 2011 Dec 1.

Abstract

Background: Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enzyme that belongs to the semicarbazide-sensitive amine oxidase (SSAO) family, which oxidatively deaminates primary amines and is implicated in leukocyte extravasation. Our aim was to investigate the alteration of soluble VAP-1/SSAO activity in plasma samples after acute intracerebral hemorrhage (ICH) and its presence in human ICH brain tissue.

Methods: VAP-1/SSAO activity was determined in plasma of 66 ICH patients and 58 healthy controls. In addition, we assessed the expression of VAP-1/SSAO in postmortem brain tissue from hemorrhagic stroke patients by Western blot and immunohistochemistry.

Results: We observed significantly higher levels of plasma VAP-1/SSAO activity in patients with ICH compared to matched elderly controls (p = 0.001). Plasma VAP-1/SSAO activity <2.7 pmol/min·mg and baseline ICH volume <17 ml were independent predictors of neurological improvement after 48 h (OR 6.8, 95% CI 1.14-41.67, p = 0.035, and OR 10.64, 95% CI 1.1-100, p = 0.041, respectively), after adjustment for baseline stroke severity. We also found that membrane-bound VAP-1/SSAO levels were lower in the perihematoma region than in the corresponding contralateral brain areas of patients deceased due to ICH (p = 0.024).

Conclusions: Our data demonstrate that plasma VAP-1/SSAO activity is increased in ICH and predicts neurological outcome, suggesting a possible contribution of the soluble protein in secondary brain damage. Furthermore, anti-VAP-1/SSAO strategies might be a promising approach to prevent neurological worsening following ICH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amine Oxidase (Copper-Containing) / blood*
  • Autopsy
  • Biomarkers / blood
  • Blotting, Western
  • Brain / enzymology*
  • Case-Control Studies
  • Cell Adhesion Molecules / blood*
  • Chi-Square Distribution
  • Female
  • Humans
  • Immunohistochemistry
  • Intracranial Hemorrhages / blood
  • Intracranial Hemorrhages / enzymology*
  • Intracranial Hemorrhages / mortality
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Prognosis
  • Spain
  • Stroke / blood
  • Stroke / enzymology*
  • Stroke / mortality
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers
  • Cell Adhesion Molecules
  • AOC3 protein, human
  • Amine Oxidase (Copper-Containing)