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.
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 humanICH brain tissue. METHODS:VAP-1/SSAO activity was determined in plasma of 66 ICHpatients and 58 healthy controls. In addition, we assessed the expression of VAP-1/SSAO in postmortem brain tissue from hemorrhagic strokepatients 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.
Authors: Serena Becchi; Alberto Buson; Jonathan Foot; Wolfgang Jarolimek; Bernard W Balleine Journal: Br J Pharmacol Date: 2017-06-10 Impact factor: 8.739
Authors: P Sun; G Esteban; T Inokuchi; J Marco-Contelles; B B Weksler; I A Romero; P O Couraud; M Unzeta; M Solé Journal: Br J Pharmacol Date: 2015-10-27 Impact factor: 8.739
Authors: Giuseppe Di Giovanni; Dubravka Svob Strac; Montse Sole; Mercedes Unzeta; Keith F Tipton; Dorotea Mück-Šeler; Irene Bolea; Laura Della Corte; Matea Nikolac Perkovic; Nela Pivac; Ilse J Smolders; Anna Stasiak; Wieslawa A Fogel; Philippe De Deurwaerdère Journal: Front Neurosci Date: 2016-11-24 Impact factor: 4.677
Authors: Christian Carpéné; Mounia Hasnaoui; Balázs Balogh; Peter Matyus; Alfredo Fernández-Quintela; Víctor Rodríguez; Josep Mercader; Maria P Portillo Journal: Oxid Med Cell Longev Date: 2016-01-05 Impact factor: 6.543