Endogenous NO blockade enhances tissue factor expression via increased Ca2+ influx through MCP-1 in endothelial cells by monocyte adhesion
Endogenous NO blockade enhances tissue factor expression via increased Ca2+ influx through MCP-1 in endothelial cells by monocyte adhesion
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DOI：
10.1161/01.atv.0000178171.61754.cd
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发表时间：
2005-09-01
影响因子：
8.7
通讯作者：
Maruyama, Y
中科院分区：
文献类型：
--
作者：
Sakamoto, T;Ishibashi, T;Maruyama, Y
目的-Ca ~（2+）在组织因子（TF）基因表达中起重要作用。我们研究了内源性一氧化氮（NO）的作用，在内皮细胞（ECs）的TF表达的诱导单核细胞adhesion和NO action.Methods和Results的机制-抑制内源性NO的N-ω-硝基-L-精氨酸甲酯（L-NAME）增强TF启动子的活性和蛋白表达诱导的人冠状动脉内皮细胞单核细胞粘附，以及EC表面TF活性。L-NAME还诱导单核细胞趋化蛋白-1（MCP-1）的表达，其被NO供体NOC 18阻断。外源性MCP-1增强单核细胞粘附诱导的TF表达，而腺病毒介导的突变体MCP-1（7 ND）的表达消除了单核细胞粘附诱导的L-NAME对TF表达的增强。单核细胞粘附于L-NAME处理的EC增加Ca 2+内流，这被NOC 18、抗MCP-1抗体或7 ND阻止。结果表明，内源性NO阻断诱导的MCP-1与CCR 2的结合，仅在单核细胞粘附于EC时才能介导Ca ~（2+）内流的增加，从而上调单核细胞粘附所触发的EC TF表达。
Objective -Ca2+ plays an important role in tissue factor (TF) gene expression. We investigated the role of endogenous nitric oxide (NO) in the induction of TF expression in endothelial cells (ECs) by monocyte adhesion and the mechanisms of NO action.Methods and Results - Inhibition of endogenous NO by N-omega-nitro-L-arginine methyl ester (L-NAME) enhanced TF promoter activity and protein expression induced in human coronary ECs by monocyte adhesion, as well as EC surface TF activity. L-NAME also induced monocyte chemoattractant protein-1 (MCP-1) expression, which was blocked by an NO donor, NOC18. Exogenous MCP-1 enhanced TF expression induced by monocyte adhesion, whereas adenovirus-mediated expression of the mutant MCP-1, 7ND, abolished the L-NAME enhancement of TF expression induced by monocyte adhesion. Monocyte attachment to L-NAME - treated ECs increased Ca2+ influx, which was prevented by NOC18, anti - MCP-1 antibody or 7ND. These results indicate that the binding of increased MCP-1 induced by endogenous NO blockade to CCR2 mediated the enhancement of Ca2+ influx only when monocytes adhered to ECs, which upregulated TF expression in ECs triggered by monocyte adhesion.Conclusion - MCP-1/CCR2 may play a role in Ca2+ influx-dependent TF regulation in the monocyte - EC interaction in the impairment of NO synthesis.