Plasma VAP-1/SSAO activity predicts intracranial hemorrhages and adverse neurological outcome after tissue plasminogen activator treatment in stroke.
OBJECTIVE
Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enzyme involved in recruitment of lymphocytes and neutrophils through its semicarbazide-sensitive amine oxidase (SSAO) activity. We aimed to study plasma VAP-1/SSAO activity in relation to the risk for intracranial bleeding complications in patients with stroke treated with tissue plasminogen activator (tPA), the greatest safety concern with this treatment.


METHODS
In 141 patients with ischemic stroke, we measured VAP-1/SSAO activity in plasma taken before tPA administration. Hemorrhagic events were classified according to brain CT criteria and functional outcomes evaluated using the National Institutes of Health Stroke Scale. We also assessed the potential therapeutic effect of blocking VAP-1/SSAO activity in a rat embolic stroke model treated with tPA.


RESULTS
We saw significantly higher levels of plasma VAP-1/SSAO activity in patients who subsequently experienced hemorrhagic transformation. Elevated plasma VAP-1/SSAO activity also predicted worse neurological outcome in these patients. In the rat model, we confirmed that use of the inhibitor semicarbazide prevented adverse effects caused by delayed tPA administration, leading to a smaller infarct volume.


CONCLUSIONS
Our data demonstrate that baseline VAP-1/SSAO activity predicts parenchymal hemorrhage after tPA, suggesting the safety of thrombolytic agents could be improved by considering VAP-1/SSAO activity. Furthermore, anti-VAP-1/SSAO drugs given with tPA may prevent neurological worsening in patients with ischemic stroke.
Neurovascular Research Laboratory, Institut de Recerca, Hospital Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
Mar
M
Hernandez-Guillamon
Lidia
L
Garcia-Bonilla
Montse
M
Solé
Victoria
V
Sosti
Mireia
M
Parés
Mireia
M
Campos
Arantxa
A
Ortega-Aznar
Carmen
C
Domínguez
Marta
M
Rubiera
Marc
M
Ribó
Manolo
M
Quintana
Carlos A
CA
Molina
José
J
Alvarez-Sabín
Anna
A
Rosell
Mercedes
M
Unzeta
Joan
J
Montaner
D000368:Aged; D000369:Aged, 80 and over; D006631:Amine Oxidase (Copper-Containing) / Q000097:blood*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000097:blood*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D020300:Intracranial Hemorrhages / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D010959:Tissue Plasminogen Activator / Q000009:adverse effects*; D016896:Treatment Outcome
D015415:Biomarkers; D015815:Cell Adhesion Molecules; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing); D010959:Tissue Plasminogen Activator