title: Endothelial gene expression and molecular changes in response to radiosurgery in in vitro and in vivo models of cerebral arteriovenous malformations.
abstract: Radiosurgery for cerebral arteriovenous malformations (AVMs) is limited to 2-year latency. There is no early marker to monitor whether the lesion is responsive to radiosurgery. In this study, we examined endothelial gene expression and molecular changes in response to radiosurgery. Gene expression of E- and P-selectin, ICAM-1, PECAM-1, VCAM-1, tissue factor, and vWF in human cerebral microvascular endothelial cells was quantified by RT-qPCR at different radiation doses and time points. Soluble E- and P-selectin, ICAM-1, VCAM-1, and tissue factor in an animal model of AVMs were quantified by ELISA at different time after radiosurgery. We found that gene expression of E- and P-selectin, ICAM-1, PECAM-1, and VCAM-1 was upregulated by radiation in a dose-dependent manner (P < .05). Gene expression of E- and P-selectin and ICAM-1 was more sensitive to irradiation than that of PECAM-1 and VCAM-1. Radiosurgery induced gene expression of P-selectin, ICAM-1, PECAM-1, and VCAM-1 was linearly correlated with time (P < .05). Radiosurgery induced elevation of soluble E- and P-selectin, ICAM-1, VCAM-1, and tissue factor in a rat model of AVMs (P < .05). Thus, a combination of these molecules measured at different time points may serve as an early predictor of responsiveness of AVMs to radiosurgery.
authors.affiliation: Australian School of Advanced Medicine, Macquarie University, 2 Technology Place, North Ryde, Sydney, NSW 2109, Australia.
authors.forename: Jian
authors.initials: J
authors.lastname: Tu
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Hu
authors.forename: Zhongbin
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004727:Endothelium / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D002538:Intracranial Arteriovenous Malformations / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D019007:P-Selectin / Q000096:biosynthesis; D016634:Radiosurgery; D051381:Rats; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1