Artikel
Cyclo-oxygenase 2 is expressed in the wall brain AVM vessels and associates with inflammation – a putative mediator of vessel wall remodeling in brain AVMs
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Veröffentlicht: | 8. Mai 2019 |
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Gliederung
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Objective: Arteriovenous malformations in the brain (bAVM) may rupture causing severe disability or death. Currently there is no medical therapy to prevent AVM hemorrhage. BAVMs are characterized by abnormally high flow that has been shown to trigger degenerative expansive remodelling in other vessels. This inflammatory remodelling is mediated by cyclo-oxygenase -2 (COX2), an induced enzyme that is the target of non-steroidal anti-inflammatory drugs. Inflammation has been reported in bAVMs with pathological vessels growth and remodeling. We investigated whether COX2 is expressed in bAVMs and whether it associates with inflammation and haemorrhage in these lesions.
Methods: Tissue was obtained from surgery of 110 bAVMs and 3 normal Circle of Willis samples from autopsy. The tissue samples were studied with immunohistochemistry.
Results: Although no COX2 expression was found in the normal Circle of Willis, COX2 expression was found in 72% (73/102) of the bAVMs, and localized to the endothelium or luminal surface of bAVM vessels in 48% of the bAVMs. In some bAVM vessels COX2 was also expressed in the medial layer. Interestingly, COX2 expression varied between different vessels of the same bAVM sample. COX2 was expressed by infiltrating inflammatory cells, and correlated with extent of inflammatory cell infiltration (r=0.4, p=0.001). COX2 expression was also found in the brain parenchyme in many cases. COX2 expression did not associate with clinical hemorrhage, nor with histological hemorrhage (hemosiderin) or presence or epilepsy. Association of COX2 expression with molecules mediating vessel remodelling is undergoing.
Conclusion: COX2 expression is induced in many bAVM vessels, as well as in the inflammatory cells that infiltrate the lesion. It seems likely that COX2 signaling participates in the regulation of vessel wall remodelling and inflammation ongoing in the bAVM. The possible role of COX2 signaling as a target for medical therapy stabilizing bAVMs merits further studies, especially since many safe COX2 inhibitors are available in clinical practice.