Australian School of Advanced Medicine, Macquarie University, 2 Technology Place, North Ryde, Sydney, NSW 2109, Australia.
Biomed Res Int. 2013;2013:408253. doi: 10.1155/2013/408253. Epub 2013 Oct 2.
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.
放射外科治疗脑动静脉畸形（AVM）的潜伏期限制在 2 年以内。目前还没有早期标志物来监测病变对放射外科治疗的反应。在这项研究中，我们研究了内皮细胞基因表达和分子变化对放射外科治疗的反应。通过 RT-qPCR 检测不同辐射剂量和时间点的人脑血管内皮细胞 E-和 P-选择素、ICAM-1、PECAM-1、VCAM-1、组织因子和 vWF 的基因表达。通过 ELISA 在 AVM 动物模型中检测不同放射外科治疗后时间点可溶性 E-和 P-选择素、ICAM-1、VCAM-1 和组织因子的含量。我们发现 E-和 P-选择素、ICAM-1、PECAM-1 和 VCAM-1 的基因表达随辐射剂量呈剂量依赖性上调（P<.05）。E-和 P-选择素和 ICAM-1 的基因表达比 PECAM-1 和 VCAM-1 对辐射更敏感。放射外科治疗诱导的 P-选择素、ICAM-1、PECAM-1 和 VCAM-1 基因表达与时间呈线性相关（P<.05）。放射外科治疗诱导 AVM 大鼠模型中可溶性 E-和 P-选择素、ICAM-1、VCAM-1 和组织因子升高（P<.05）。因此，在不同时间点测量的这些分子的组合可能作为 AVM 对放射外科治疗反应的早期预测指标。
