RNA in blood is altered prior to hemorrhagic transformation in ischemic stroke.
RNA in blood is altered prior to hemorrhagic transformation in ischemic stroke.
复制标题
DOI：
10.1002/ana.23883
复制
发表时间：
2013-08
影响因子：
11.2
通讯作者：
Sharp, Frank R.
中科院分区：
文献类型：
--
作者：
Jickling, Glen C.;Ander, Bradley P.;Stamova, Boryana;Zhan, Xinhua;Liu, Dazhi;Rothstein, Lena;Verro, Piero;Khoury, Jane;Jauch, Edward C.;Pancioli, Arthur M.;Broderick, Joseph P.;Sharp, Frank R.
出血性转化（HT）是缺血性中风的主要并发症，会导致预后恶化并增加死亡率。血脑屏障的破坏是 HT 发病机制的一个核心特征，白细胞可能参与这一过程。我们试图确定发生 HT 的缺血性中风在溶栓治疗前的中风发作 3 小时内血液中的 RNA 表达是否存在差异。在溶栓治疗前获取中风患者的血液样本，并通过微阵列分析评估白细胞RNA。将发生 HT 的中风 (n=11) 与无 HT 的中风 (n=33) 和对照组 (n=14) 进行比较。鉴定基因（校正 p 值 <0.05，倍数变化 ≥|1.2|）并进行功能分析。在第二个卒中队列 (n=52) 中，使用交叉验证评估了卒中 HT 的 RNA 预测。发生 HT 的缺血性中风在接受溶栓治疗之前，循环白细胞中有 29 个基因存在差异表达。一组 6 个基因可以预测随后发展为 HT 的中风，其敏感性为 80%，特异性为 70.2%。描述了参与人类中风 HT 的关键途径，包括双调蛋白（一种调节基质金属蛋白酶 9 的生长因子）；涉及 SMAD4、INPP5D 和 IRAK3 的转化生长因子-β 信号传导发生转变；以及凝血因子 V 和 VIII 的破坏。已确定的基因与炎症和凝血的差异相对应，这些差异可能导致缺血性中风中的HT。鉴于 HT 对中风结果的不利影响，有必要对已确定的基因和通路进行进一步评估，以确定它们作为减少 HT 治疗靶点和作为 HT 风险标记的潜力。
Hemorrhagic transformation (HT) is a major complication of ischemic stroke that worsens outcomes and increases mortality. Disruption of the blood brain barrier is a central feature to HT pathogenesis, and leukocytes may contribute to this process. We sought to determine whether ischemic strokes that develop HT have differences in RNA expression in blood within 3 hours of stroke onset prior to treatment with thrombolytic therapy. Stroke patient blood samples were obtained prior to treatment with thrombolysis, and leukocyte RNA assessed by microarray analysis. Strokes that developed HT (n=11) were compared to strokes without HT (n=33) and controls (n=14). Genes were identified (corrected p-value <0.05, fold change ≥|1.2|) and functional analysis performed. RNA prediction of HT in stroke was evaluated using cross-validation, and in a second stroke cohort (n=52). Ischemic strokes that developed HT had differential expression of 29 genes in circulating leukocytes prior to treatment with thrombolytic therapy. A panel of 6 genes could predict strokes that later developed HT with 80% sensitivity and 70.2% specificity. Key pathways involved in HT of human stroke are described, including amphiregulin, a growth factor that regulates matrix metalloproteinase-9; a shift in transforming growth factor-beta signaling involving SMAD4, INPP5D and IRAK3; and a disruption of coagulation factors V and VIII. Identified genes correspond to differences in inflammation and coagulation that may predispose to HT in ischemic stroke. Given the adverse impact of HT on stroke outcomes, further evaluation of the identified genes and pathways is warranted to determine their potential as therapeutic targets to reduce HT and as markers of HT risk.
登录
查看更多内容
影响因子：
11.2
作者：
Jickling, Glen C.;Stamova, Boryana;Ander, Bradley P.;Zhan, Xinhua;Tian, Yingfang;Liu, Dazhi;Xu, Huichun;Johnston, S. Claiborne;Verro, Piero;Sharp, Frank R.
通讯作者：
Sharp, Frank R.
影响因子：
6.5
作者：
Chung, E;Cook, PW;Coffey, RJ
通讯作者：
Coffey, RJ
影响因子：
32.4
作者：
Cao, Wei;Yang, Yiqing;Zhang, Jingwu Z.
通讯作者：
Zhang, Jingwu Z.
影响因子：
168.9
作者：
Gallione, CJ;Repetto, GM;Marchuk, DA
通讯作者：
Marchuk, DA
影响因子：
8.3
作者：
Castellanos, Mar;Sobrino, Tomas;Davalos, Antoni
通讯作者：
Davalos, Antoni