Vascular adhesion protein-1 in human ischaemic stroke.
OBJECTIVE
Leukocyte extravasation exacerbates tissue injury after ischaemic stroke. Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule with the potential capacity to guide transmigration of inflammatory cells into ischaemic brain. Moreover, VAP-1 could worsen ischaemic brain injury due to its function as a semicarbazide-sensitive amine oxidase (SSAO) producing toxic metabolites from primary amines. The purpose of this study was to elucidate these aspects of VAP-1-function in the pathogenesis of human ischaemic stroke.


METHODS
We studied VAP-1 expression in infarcted and control brains post mortem using immunohistochemistry. Levels of soluble VAP-1 (sVAP-1) in the serum of patients with acute stroke and in control sera were determined using enzyme-linked immunosorbent assay.


RESULTS
In the acute phase of ischaemic stroke, the frequency of VAP-1-stained vessels was strongly diminished in the ipsilateral hemisphere but in the contralateral hemisphere it was comparable with the expression in the control brains. In the serum of acute stroke patients with a symptom duration <6 h the level of sVAP-1 was significantly increased (652 +/- 224 ng/ml; mean +/- SD) when compared with an age- and sex-matched control group (542 +/- 104 ng/ml; P < 0.05).


CONCLUSIONS
As both cell surface and sVAP-1 possess vasculopathy-promoting SSAO enzymatic activity, our results imply that by inducing SSAO-derived toxic metabolites, VAP-1 might aggravate ischaemic vascular changes. The subsequent release of sVAP-1 into circulation could be further examined as a potential marker of early ischaemic vasculopathy.
Airas
L
L
Department of Neurology, MediCity Research Laboratory, Turku University, Turku, Finland. laura.airas@utu.fi
Lindsberg
P J
PJ
Karjalainen-Lindsberg
M-L
ML
Mononen
I
I
Kotisaari
K
K
Smith
D J
DJ
Jalkanen
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D001344:Autopsy; D002545:Brain Ischemia / Q000473:pathology* / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000473:pathology; D012016:Reference Values; D012795:Sialoglycoproteins / Q000378:metabolism; D020521:Stroke / Q000473:pathology* / Q000503:physiopathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D015815:Cell Adhesion Molecules; D012795:Sialoglycoproteins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; C076668:AOC3 protein, human; D006631:Amine Oxidase (Copper-Containing)