Abstract | AIMS: METHODS: Human heart microvascular endothelial cells (HHMEC) and human umbilical vein endothelial cells (HUVEC) were treated with interleukin-1β (IL-1β) (200U/mL) or thrombin (5U/mL) and co-treated with or without levosimendan (0.1-10μM) for 2-24h. In addition, flow experiments were performed. Effects on plasminogen activator inhibitor-1 (PAI-1) and tissue factor (TF) expression and activity were measured by rt-PCR, specific ELISA and flow cytometry. RESULTS: Treatment with IL-1β or thrombin significantly increased the expression of PAI-1 and TF in endothelial cells. Co-treatment with levosimendan strongly attenuated the effects of IL-1β and thrombin on PAI-1 and TF mRNA by up to 50% and 45%, in a dose- and time-dependent manner. Similar results were obtained under flow conditions. Furthermore, co-treatment with levosimendan dampened the antigen production of PAI-1 and the surface expression of TF by 35% and 45%, respectively. Additionally, levosimendan diminished both TF and PAI-1 activity. CONCLUSION:
Levosimendan down-regulates the expression of the pro-thrombotic and anti-fibrinolytic biomolecules TF and PAI-1 in activated human endothelial cells. Our findings may, at least in part, explain some of the beneficial effects of levosimendan after myocardial reperfusion.
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Authors | Konstantin A Krychtiuk, Christoph Kaun, Philipp J Hohensinner, Stefan Stojkovic, Jacqueline Seigner, Stefan P Kastl, Andreas Zuckermann, Wolfgang Eppel, Sabine Rauscher, Rainer de Martin, Gerald Maurer, Kurt Huber, Johann Wojta, Walter S Speidl |
Journal | Vascular pharmacology
(Vascul Pharmacol)
Vol. 90
Pg. 44-50
(03 2017)
ISSN: 1879-3649 [Electronic] United States |
PMID | 28192257
(Publication Type: Journal Article)
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Copyright | Copyright © 2017 Elsevier Inc. All rights reserved. |
Chemical References |
- Fibrinolytic Agents
- Hydrazones
- Interleukin-1beta
- Plasminogen Activator Inhibitor 1
- Pyridazines
- SERPINE1 protein, human
- Simendan
- Thromboplastin
- Thrombin
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Topics |
- Cells, Cultured
- Dose-Response Relationship, Drug
- Down-Regulation
- Fibrinolysis
(drug effects)
- Fibrinolytic Agents
(pharmacology)
- Human Umbilical Vein Endothelial Cells
(drug effects, metabolism)
- Humans
- Hydrazones
(pharmacology)
- Interleukin-1beta
(pharmacology)
- Plasminogen Activator Inhibitor 1
(metabolism)
- Pyridazines
(pharmacology)
- Simendan
- Thrombin
(pharmacology)
- Thromboplastin
(metabolism)
- Time Factors
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