Nitric Oxide Increases Arterial Endotheial Permeability through Mediating VE-Cadherin Expression during Arteriogenesis.
Nitric Oxide Increases Arterial Endotheial Permeability through Mediating VE-Cadherin Expression during Arteriogenesis.
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一氧化氮通过介导动脉生成过程中 VE-钙粘蛋白的表达来增加动脉内皮渗透性
DOI：
10.1371/journal.pone.0127931
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Schaper W
中科院分区：
文献类型：
--
作者：
Yang B;Cai B;Deng P;Wu X;Guan Y;Zhang B;Cai W;Schaper J;Schaper W
巨噬细胞侵入是动脉形成过程中的重要事件，但其机制仍不完全清楚。本研究测试的假设，一氧化氮（NO）和VE-钙粘蛋白，血管通透性的两个关键介质，有助于这一事件在大鼠缺血后肢模型。此外，在培养的HUVECs中，还研究了NO对VE-caherin表达和内皮通透性的影响。结果发现：1）在正常小动脉血管（NAV）中，内皮细胞（EC）中eNOS呈中度表达，而iNOS则很少表达;而在单纯股动脉结扎诱导的侧支血管中，eNOS和iNOS均显著上调（P<0.05）。诱导型NOS主要在平滑肌细胞中表达，但也可在其他血管细胞和巨噬细胞中表达; 2）在NAV中，VE-钙粘蛋白在EC中表达较强。在CV中，VE-钙粘蛋白显著下调，具有不连续和点状模式。NO合成酶抑制剂L-NAME可抑制CV中VE-钙粘蛋白的下调; 3）正常大鼠股薄肌伊文思蓝外渗（EBE）较低，血管壁未见FITC-右旋糖酐渗漏，血管周围未见巨噬细胞浸润。相比之下，股动脉结扎大鼠的EBE显着增加，检测到FITC-右旋糖酐泄漏和CV中巨噬细胞数量增加，NONOate给药进一步增强，但L-NAME补充剂抑制了这种情况; 4）体外实验证实，NO产生的增加减少了VE-cadherin的表达，与HUVEC的渗透性增加相关。总之，我们的数据首次揭示了VE-钙粘蛋白的表达谱和血管通透性的改变，表明NO介导的VE-钙粘蛋白途径可能是一个重要的机制，负责，至少部分，在动脉生成过程中的巨噬细胞侵袭。
Macrophage invasion is an important event during arteriogenesis, but the underlying mechanism is still only partially understood. The present study tested the hypothesis that nitric oxide (NO) and VE-cadherin, two key mediators for vascular permeability, contribute to this event in a rat ischemic hindlimb model. In addition, the effect of NO on expression of VE-caherin and endothelial permeability was also studied in cultured HUVECs. We found that: 1) in normal arteriolar vessels (NAV), eNOS was moderately expressed in endothelial cells (EC) and iNOS was rarely detected. In contrast, in collateral vessels (CVs) induced by simple femoral artery ligation, both eNOS and iNOS were significantly upregulated (P<0.05). Induced iNOS was found mainly in smooth muscle cells, but also in other vascular cells and macrophages; 2) in NAV VE-cadherin was strongly expressed in EC. In CVs, VE-cadherin was significantly downregulated, with a discontinuous and punctate pattern. Administration of nitric oxide donor DETA NONOate (NONOate) further reduced the amounts of Ve-cadherin in CVs, whereas NO synthase inhibitor L-NAME inhibited downregulation of VE-cadherin in CVs; 3) in normal rats Evans blue extravasation (EBE) was low in the musculus gracilis, FITC-dextron leakage was not detected in the vascular wall and few macrophages were observed in perivascular space. In contrast, EBE was significantly increased in femoral artery ligation rats, FITC-dextron leakage and increased amounts of macrophages were detected in CVs, which were further enhanced by administration of NONOate, but inhibited by L-NAME supplement; 4) in vitro experiments confirmed that an increase in NO production reduced VE-cadherin expression, correlated with increases in the permeability of HUVECs. In conclusion, our data for the first time reveal the expression profile of VE-cadherin and alterations of vascular permeability in CVs, suggesting that NO-mediated VE-cadherin pathway may be one important mechanism responsible, at least in part, for macrophage invasion during arteriogenesis.
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影响因子：
4
作者：
Dejana, Elisabetta;Orsenigo, Fabrizio;Lampugnani, Maria Grazia
通讯作者：
Lampugnani, Maria Grazia
DOI：
10.1016/s0006-291x(03)00546-1
发表时间：
2003-04-25
影响因子：
3.1
作者：
González, D;Herrera, B;Rojas, A
通讯作者：
Rojas, A
DOI：
10.1073/pnas.96.17.9815
发表时间：
1999-08-17
影响因子：
11.1
作者：
Corada, M;Mariotti, M;Dejana, E
通讯作者：
Dejana, E
动脉生成过程中整合素 α 5β 1 和 α V β 3 以及粘着斑激酶 (FAK) 的激活。
影响因子：
4.3
作者：
Cai, Wei-Jun;Li, Ming Bo;Wu, Xiaoqiong;Wu, Song;Zhu, Wu;Chen, Dan;Luo, Mingying;Eitenmueller, Inka;Kampmann, Andreas;Schaper, Jutta;Schaper, Wolfgang
通讯作者：
Schaper, Wolfgang
影响因子：
16
作者：
Eliceiri, BP;Paul, R;Cheresh, DA
通讯作者：
Cheresh, DA