Endogenous NO blockade enhances tissue factor expression via increased Ca2+ influx through MCP-1 in endothelial cells by monocyte adhesion

Takayuki Sakamoto, Toshiyuki Ishibashi, Nobuo Sakamoto, Koichi Sugimoto, Kensuke Egashira, Hiroshi Ohkawara, Kenji Nagata, Keiko Yokoyama, Masashi Kamioka, Toshihiro Ichiki, Naotoshi Sugimoto, Masahiko Kurabayashi, Koji Suzuki, Yoh Takuwa, Yukio Maruyama

    研究成果: Contribution to journalArticle査読

    28 被引用数 (Scopus)

    抄録

    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 Nω-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.

    本文言語英語
    ページ(範囲)2005-2011
    ページ数7
    ジャーナルArteriosclerosis, thrombosis, and vascular biology
    25
    9
    DOI
    出版ステータス出版済み - 9 2005

    All Science Journal Classification (ASJC) codes

    • 循環器および心血管医学

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