Proteomics identification of radiation-induced changes of membrane proteins in the rat model of arteriovenous malformation in pursuit of targets for brain AVM molecular therapy

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.Electronic supplementary materialThe online version of this article (10.1186/s12014-018-9217-x) contains supplementary material, which is available to authorized users.

Microenvironment changes in arteriovenous malformations after stereotactic radiation

“…The exact mechanism and micro-environmental changes in AVMs in response to radiation has yet to be fully elucidated, though many studies have used ex-vivo tissue models, animal models and human histopathology to try and determine the response to radiation (Liu et al, 2012 ; Simonian et al, 2018 ; Xu et al, 2018 ). It is understood that radiation results in cellular damage, particularly to the vasculature endothelium, which demonstrates some of the earliest ultrastructural changes after radiation and are considered the most radiosensitive cells of the vessel wall.…”

Biomarkers for Biodosimetry and Their Role in Predicting Radiation Injury

“…Accidental or intentional radiation exposures are an ongoing concern for the public. Ionizing radiation can directly produce DNA damage, chromosomal aberrations, protein destruction or alteration, and metabolite modification [Simonian et al, 2018]. In both animal models and human patients, differences in gene (RNA expression) response to radiation can cause variation in who develops toxicities and what pathways are altered [Barnett et al, 2015;Chakraborty et al, 2020].…”