Knockdown of Nrf2 inhibits the angiogenesis of rat cardiac micro-vascular endothelial cells under hypoxic conditions.
Knockdown of Nrf2 inhibits the angiogenesis of rat cardiac micro-vascular endothelial cells under hypoxic conditions.
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DOI：
10.7150/ijbs.5887
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发表时间：
2013
影响因子：
9.2
通讯作者：
Jing T
中科院分区：
文献类型：
--
作者：
Kuang L;Feng J;He G;Jing T
血管生成在心肌梗死（MI）后的心肌修复中发挥着重要作用。心脏微血管内皮细胞（CMEC）是心肌血管生成过程的重要参与者。最近的研究表明，核因子-红细胞2相关因子2（Nrf2）是内源性抗氧化防御系统的主要转录因子，在心血管系统中发挥心脏保护作用。然而，Nrf2在心肌血管生成过程中的作用及相应机制尚不完全清楚。因此，本研究调查了Nrf2在大鼠CMEC缺氧血管生成中的作用。采用Trans-well实验、三维Matrigel实验测定细胞迁移和血管形成。实时RT-PCR、ELISA和Western blot检测mRNA和蛋白表达。在这里，我们报道了缺氧条件下Nrf2和血红素加氧酶-1（HO-1）的mRNA和蛋白表达暂时上调。此外，Nrf2的敲低显着抑制了大鼠CMEC向缺氧的迁移和血管形成，缺氧条件下转染后48小时，Nrf2的敲低还显着降低了HO-1和血管内皮生长因子（VEGF）的表达。最后，用 Nrf2 过表达慢病毒载体转染 CMEC 上调了 HO-1 表达，同时缺氧诱导的细胞迁移和血管形成增加，而这种效应在 ZnPP（一种 HO-1 抑制剂）存在下大大减弱。综上所述，这些结果表明Nrf2可能介导缺氧条件下CMEC的血管生成，HO-1通过Nrf2参与调节CMEC的血管生成。因此，Nrf2是CMEC中缺氧条件介导的血管生成的有效调节剂，这可能为MI后的心肌修复提供治疗策略。
Angiogenesis plays an important role in myocardial repair after myocardial infarction (MI). Cardiac micro-vascular endothelial cells (CMECs) are important participants in myocardial angiogenesis processes. Recent studies have revealed that Nuclear factor-erythroid 2-related factor 2 (Nrf2), a master transcription factor of endogenous anti-oxidative defense systems, exerts cardio-protection in the cardiovascular system. However, the role of Nrf2 in the process of myocardial angiogenesis and corresponding mechanisms are not fully understood. Thus, the present study investigated the role of Nrf2 in the angiogenesis of rat CMECs to hypoxia. Trans-well assay, three-dimensional Matrigel assay were used to determine cell migration and vascular tube formation. Real-time RT-PCR, ELISA and Western blot were measured mRNA and protein expression. Here, we report that the mRNA and protein expression of Nrf2 and heme oxygenase-1(HO-1) were temporarily upregulated under hypoxic condition. Furthermore, knock down of Nrf2 significantly suppressed the migration and vascular tube formation of rat CMECs to hypoxia, Nrf2 knockdown also significantly decreased HO-1 and vascular endothelial growth factor (VEGF) expression at 48 h after transfection under hypoxic condition. Finally, transfection of CMECs with the Nrf2 over-expressing lentiviral vector upregulated HO-1 expression with a concomitant increase in cell migration and vascular tube formation induced by hypoxia, and this effect was greatly attenuated in the presence of ZnPP (a HO-1 inhibitor). Taken together, these results suggest that Nrf2 may mediate the angiogenesis of CMECs under hypoxic condition, and HO-1 is involved in regulating the angiogenesis of CMECs through Nrf2. Therefore, Nrf2 is a potent regulator of hypoxia-condition mediated angiogenesis in CMECs, which may provide a therapeutic strategy for myocardial repair after MI.
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影响因子：
20.1
作者：
Dai, Guohao;Vaughn, Saran;Gimbrone, Michael A., Jr.
通讯作者：
Gimbrone, Michael A., Jr.
影响因子：
4.6
作者：
Polotsky, Vsevolod Y.;Savransky, Vladimir;Shimoda, Larissa A.
通讯作者：
Shimoda, Larissa A.
影响因子：
4
作者：
Feng, Jian;Zhang, Ping;He, Guoxiang
通讯作者：
He, Guoxiang
RNA干扰沉默基质相互作用分子1抑制内皮祖细胞的增殖和迁移
DOI：
10.1016/j.bbrc.2010.06.088
发表时间：
2010-07-23
影响因子：
3.1
作者：
Kuang, Chun-yan;Yu, Yang;Huang, Lan
通讯作者：
Huang, Lan
影响因子：
10.8
作者：
Tongers, Joern;Knapp, Julia-Marie;Wollert, Kai C.
通讯作者：
Wollert, Kai C.