Abstract
BackgroundRapid identification of novel targets and advancement of a vascular targeting strategy requires a comprehensive assessment of AVM endothelial membrane protein changes in response to irradiation. The aim of this study is to provide additional potential target protein molecules for evaluation in animal trials to promote intravascular thrombosis in AVM vessels post radiosurgery.MethodsWe employed in vivo biotinylation methodology that we developed, to label membrane proteins in the rat model of AVM post radiosurgery. Mass spectrometry expression (MSE) analysis was used to identify and quantify surface protein expression between irradiated and non irradiated rats, which mimics a radiosurgical treatment approach.ResultsOur proteomics data revealed differentially expressed membrane proteins between irradiated and non irradiated rats, e.g. profilin-1, ESM-1, ion channel proteins, annexin A2 and lumican.ConclusionThis work provides additional potential target protein molecules for evaluation in animal trials to promote intravascular thrombosis in AVM vessels post radiosurgery.
Highlights
Brain AVMs are the major cause of hemorrhagic stroke in adults and young children with each haemorrhage caring a 50% risk of death or morbidity [1]
We have developed an animal model of AVM and demonstrated the ability of stimulating thrombosis in AVM vessels after radiosurgery by nonligand vascular targeting approach, only small vessels showed a sign of thrombosis, and the non-ligand injection is not safe for use in humans [6,7,8]
We have developed in vitro and in vivo biotinylation perfusion methodology to label endothelial cell surface proteins in murine bEnd. 3 cell cultures and the animal model of AVM [9, 10] and we have shown the feasibility of employing proteomics methods on the arteriovenous fistula (AVF) tissues harvested from the animal model [9, 10]
Summary
Brain AVMs are the major cause of hemorrhagic stroke in adults and young children with each haemorrhage caring a 50% risk of death or morbidity [1]. Radiosurgery is relatively safe when treating small lesions < 2.6 cm in diameter, without the risk of high radiation exposure to the surrounding tissues. Simonian et al Clin Proteom (2018) 15:43 these obstacles To achieve this goal, we have developed in vitro and in vivo biotinylation perfusion methodology to label endothelial cell surface proteins in murine bEnd. 3 cell cultures and the animal model of AVM [9, 10] and we have shown the feasibility of employing proteomics methods on the arteriovenous fistula (AVF) tissues harvested from the animal model [9, 10]. We employ our in vivo methodology to label, identify and quantify the differentially expressed membrane proteins in the irradiated and non irradiated animals using a labelfree quantitative mass spectrometry of expression (MSE) technique. The aim of this study is to provide additional potential target protein molecules for evaluation in animal trials to promote intravascular thrombosis in AVM vessels post radiosurgery
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