| Carbon monoxide (CO)-releasing molecule-derived CO regulates tissue factor and plasminogen activator inhibitor type 1 in human endothelial cells. | |
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MedLine Citation:
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PMID: 22819264 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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INTRODUCTION: Heme oxygenase-1 (HO-1) is the rate limiting enzyme that catalyzes the conversion of heme into biliverdin, free iron, and carbon monoxide (CO). The first human case of HO-1 deficiency showed abnormalities in blood coagulation and the fibrinolytic system. Thus, HO-1 or HO-1 products, such as CO, might regulate coagulation and the fibrinolytic system. This study examined whether tricarbonyldichlororuthenium (II) dimer (CORM-2), which liberates CO, modulates the expression of tissue factor (TF) and plasminogen activator inhibitor type 1 (PAI-1) in human umbilical vein endothelial cells (HUVECs), and TF expression in peripheral blood mononuclear cells (PBMCs). Additionally, we examined the mechanism by which CO exerts its effects. MATERIALS AND METHODS: HUVECs were pretreated with 50μM CORM-2 for 3hours, and stimulated with tumor necrosis factor-α (TNF-α, 10ng/ml) for an additional 0-5hours. PBMCs were pretreated with 50-100μM CORM-2 for 1hour followed by stimulating with lipopolysaccharid (LPS, 10ng/ml) for additional 0-9hours. The mRNA and protein levels were determined by RT-PCR and western blotting, respectively. RESULTS: Pretreatment with CORM-2 significantly inhibited TNF-α-induced TF and PAI-1 up-regulation in HUVECs, and LPS-induced TF expression in PBMCs. CORM-2 inhibited TNF-α-induced activation of p38 MAPK, ERK1/2, JNK, and NF-κB signaling pathways in HUVECs. CONCLUSIONS: CORM-2 suppresses TNF-α-induced TF and PAI-1 up-regulation, and MAPKs and NF-κB signaling pathways activation by TNF-α in HUVECs. CORM-2 suppresses LPS-induced TF up-regulation in PBMCs. Therefore, we envision that the antithrombotic activity of CORM-2 might be used as a pharmaceutical agent for the treatment of various inflammatory conditions. |
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Authors:
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Keiko Maruyama; Eriko Morishita; Takeo Yuno; Akiko Sekiya; Hidesaku Asakura; Shigeki Ohtake; Akihiro Yachie |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-7-19 |
Journal Detail:
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Title: Thrombosis research Volume: - ISSN: 1879-2472 ISO Abbreviation: - Publication Date: 2012 Jul |
Date Detail:
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Created Date: 2012-7-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0326377 Medline TA: Thromb Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012. Published by Elsevier Ltd. |
Affiliation:
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Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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