Pharmacological inhibition of epidermal growth factor receptor attenuates intracranial aneurysm formation by modulating the phenotype of vascular smooth muscle cells.
Pharmacological inhibition of epidermal growth factor receptor attenuates intracranial aneurysm formation by modulating the phenotype of vascular smooth muscle cells.
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表皮生长因子受体的药理学抑制通过调节血管平滑肌细胞的表型来减弱颅内动脉瘤的形成
DOI：
10.1111/cns.13735
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发表时间：
2022-01
影响因子：
5.5
通讯作者：
Liu J
中科院分区：
文献类型：
--
作者：
Luo Y;Tang H;Zhang Z;Zhao R;Wang C;Hou W;Huang Q;Liu J
研究药物抑制表皮生长因子受体（EGFR）对颅内动脉瘤（IA）发生的影响。通过免疫荧光（IF）分析人IA样本的p-EGFR和α平滑肌肌动蛋白（α-SMA）表达。建立IA大鼠模型以评价EGFR抑制剂厄洛替尼减弱IA发生率的能力。我们通过病理学和蛋白质组学检测分析大脑前动脉组织中p-EGFR及相关蛋白的表达，并通过血管铸型评估各组动脉瘤的发生率。提取大鼠血管平滑肌细胞（VSMC）和内皮细胞，并用于在有或无厄洛替尼处理的流动室中建立体外共培养模型。我们通过免疫印迹分析确定VSMCs中的p-EGFR和相关蛋白表达。表皮生长因子受体激活被发现在人类IA血管壁和大鼠大脑前动脉壁。厄洛替尼治疗通过抑制大鼠IA血管壁中血管重塑和VSMC的促炎性转化显著降低IA的发生率。大鼠VSMCs中EGFR的激活和大鼠VSMCs的表型调节与体外剪切应力的强度相关，厄洛替尼治疗降低了大鼠VSMCs的表型调节。体外实验还显示，TNF-α可诱导人脑VSMCs中EGFR活化。这些结果表明，EGFR在IA的启动中起着关键作用，EGFR抑制剂厄洛替尼通过调节VSMC的表型调节来保护大鼠免于IA的启动。在人颅内动脉瘤组织和大鼠颅内动脉瘤模型中发现表皮生长因子受体（EGFR）活化。厄洛替尼对EGFR的药理学抑制通过调节血管平滑肌细胞的表型来减轻颅内动脉瘤。
To study the effect of pharmacological inhibition of epidermal growth factor receptor (EGFR) on intracranial aneurysm (IA) initiation. Human IA samples were analyzed for the expression of p‐EGFR and alpha smooth muscle actin (α‐SMA) by immunofluorescence (IF). Rat models of IA were established to evaluate the ability of the EGFR inhibitor, erlotinib, to attenuate the incidence of IA. We analyzed anterior cerebral artery tissues by pathological and proteomic detection for the expression of p‐EGFR and relevant proteins, and vessel casting was used to evaluate the incidence of aneurysms in each group. Rat vascular smooth muscle cells (VSMCs) and endothelial cells were extracted and used to establish an in vitro co‐culture model in a flow chamber with or without erlotinib treatment. We determined p‐EGFR and relevant protein expression in VSMCs by immunoblotting analysis. Epidermal growth factor receptor activation was found in human IA vessel walls and rat anterior cerebral artery walls. Treatment with erlotinib markedly attenuated the incidence of IA by inhibiting vascular remodeling and pro‐inflammatory transformation of VSMC in rat IA vessel walls. Activation of EGFR in rat VSMCs and phenotypic modulation of rat VSMCs were correlated with the strength of shear stress in vitro, and treatment with erlotinib reduced phenotypic modulation of rat VSMCs. In vitro experiments also revealed that EGFR activation could be induced by TNF‐α in human brain VSMCs. These results suggest that EGFR plays a critical role in the initiation of IA and that the EGFR inhibitor erlotinib protects rats from IA initiation by regulating phenotypic modulation of VSMCs. Epidermal growth factor receptor (EGFR) activation was found in human intracranial aneurysm tissues and rat intracranial aneurysm models. Pharmacological inhibition of EGFR by erlotinib attenuates intracranial aneurysm through regulating phenotype of vascular smooth muscle cells.
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DOI：
10.1073/pnas.1323761111
发表时间：
2014-02-04
影响因子：
11.1
作者：
Chang, Shun-Fu;Chen, Li-Jing;Chiu, Jeng-Jiann
通讯作者：
Chiu, Jeng-Jiann
无标记定量蛋白质组学比较兔动脉瘤模型和人颅内动脉瘤的蛋白质组分析
影响因子：
5.5
作者：
Liu Y;Song Y;Liu P;Li S;Shi Y;Yu G;Quan K;Fan Z;Li P;An Q;Zhu W
通讯作者：
Zhu W
影响因子：
15.9
作者：
Cascone, Tina;Herynk, Matthew H.;Heymach, John V.
通讯作者：
Heymach, John V.
DOI：
10.1152/ajplung.00311.2006
发表时间：
2007-03-01
影响因子：
4.9
作者：
Lee, Chiang-Wen;Lin, Chih-Chung;Yang, Chuen-Mao
通讯作者：
Yang, Chuen-Mao
影响因子：
4.8
作者：
Eguchi, S;Dempsey, PJ;Inagami, T
通讯作者：
Inagami, T