| Item type |
学術雑誌論文 / Journal Article(1) |
| 公開日 |
2017-10-03 |
| タイトル |
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タイトル |
Fluvastatin Upregulates the Expression of Tissue Factor Pathway Inhibitor in Human Umbilical Vein Endothelial Cells |
| 言語 |
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言語 |
eng |
| 資源タイプ |
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資源タイプ識別子 |
http://purl.org/coar/resource_type/c_6501 |
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資源タイプ |
journal article |
| ID登録 |
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ID登録 |
10.24517/00014248 |
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ID登録タイプ |
JaLC |
| 著者 |
Sekiya, Akiko
Morishita, Eriko
Maruyama, Keiko
Torishima, Hiroki
Ohtake, Shigeki
|
| 著者別表示 |
關谷, 暁子
森下, 英理子
大竹, 茂樹
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| 書誌情報 |
Journal of Atherosclerosis and Thrombosis
巻 22,
号 7,
p. 660-668,
発行日 2015-01-01
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| ISSN |
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収録物識別子タイプ |
ISSN |
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収録物識別子 |
1340-3478 |
| NCID |
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収録物識別子タイプ |
NCID |
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収録物識別子 |
AA11018976 |
| DOI |
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関連タイプ |
isIdenticalTo |
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識別子タイプ |
DOI |
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関連識別子 |
10.5551/jat.28175 |
| 出版者 |
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出版者 |
Japan Atherosclerosis Society = 日本動脈硬化学会 |
| 抄録 |
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内容記述タイプ |
Abstract |
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内容記述 |
Aim: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are cholesterol-lowering drugs with a variety of pleiotropic effects including antithrombotic properties. Tissue factor pathway inhibitor (TFPI), which is produced predominantly in endothelial cells and platelets, inhibits the initiating phase of clot formation. We investigated the effect of fluvastatin on TFPI expression in cultured endothelial cells. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with fluvastatin (0–10μM). The expression of TFPI mRNA and antigen were detected by RT-PCR and western blotting, respectively. The effects of mevalonate intermediates, small GTP-binding inhibitors, and signal transduction inhibitors were also evaluated to identify which pathway was involved. A luciferase reporter assay was performed to evaluate the effect of fluvastatin on TFPI transcription. The stability of TFPI mRNA was estimated by quantitating its levels after actinomycin D treatment. Results: Fluvastatin increased TFPI mRNA expression and antigen in HUVECs. Fluvastatin-induced TFPI expression was reversed by co-treatment with mevalonate or geranylgeranylpyrophosphate (GGPP). NSC23766 and Y-27632 had no effect on TFPI expression. SB203580, GF109203, and LY294002 reduced fluvastatin-induced TFPI upregulation. Moreover, fluvastatin did not significantly affect TFPI promoter activity. TFPI mRNA degradation in the presence of actinomycin D was delayed by fluvastatin treatment. Conclusions: Fluvastatin increases endothelial TFPI expression through inhibition of mevalonate-, GGPP-, and Cdc42-dependent signaling pathways, and activation of the p38 MAPK, PI3K, and PKC pathways. This study revealed unknown mechanisms of the anticoagulant effect of statins and gave a new insight to its therapeutic potential for the prevention of thrombotic diseases. |
| 権利 |
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権利情報 |
Copyright © Japan Atherosclerosis Society |
| 著者版フラグ |
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出版タイプ |
VoR |
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出版タイプResource |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| 関連URI |
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識別子タイプ |
URI |
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関連識別子 |
http://www.j-athero.org/ |
| 関連URI |
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識別子タイプ |
URI |
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関連識別子 |
https://www.jstage.jst.go.jp/browse/jat |
ME-PR-SEKIYA-A-660.pdf (252.4 kB)
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