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Krychtiuk, Konstantin A.; Watzke, Lukas; Kaun, Christoph; Buchberger, Elisabeth; Hofer-Warbinek, Renate; Demyanets, Svitlana; Pisoni, Julia; Kastl, Stefan P.; Rauscher, Sabine; Gröger, Marion; Aliabadi, Arezu; Zuckermann, Andreas; Maurer, Gerald; Martin, Rainer de; Huber, Kurt; Speidl, Walter S.; Wojta, Johann

Levosimendan exerts anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro

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  • Media type: E-Article
  • Title: Levosimendan exerts anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro
  • Contributor: Krychtiuk, Konstantin A.; Watzke, Lukas; Kaun, Christoph; Buchberger, Elisabeth; Hofer-Warbinek, Renate; Demyanets, Svitlana; Pisoni, Julia; Kastl, Stefan P.; Rauscher, Sabine; Gröger, Marion; Aliabadi, Arezu; Zuckermann, Andreas; Maurer, Gerald; Martin, Rainer de; Huber, Kurt; Speidl, Walter S.; Wojta, Johann
  • imprint: Georg Thieme Verlag KG, 2015
  • Published in: Thrombosis and Haemostasis
  • Language: English
  • DOI: 10.1160/th14-06-0549
  • ISSN: 0340-6245; 2567-689X
  • Keywords: Hematology
  • Origination:
  • Footnote:
  • Description: <jats:title>Summary</jats:title><jats:p>Levosimendan is a positive inotropic drug for the treatment of acute decompensated heart failure (HF). Clinical trials showed that levosimendan was particularly effective in HF due to myocardial infarction. Myocardial necrosis induces a strong inflammatory response, involving chemoattractants guiding polymorphonuclear neutrophils (PMN) into the infarcted myocardial tissue. Our aim was to examine whether levosimendan exhibits anti-inflammatory effects on human adult cardiac myocytes (HACM) and human heart microvascular endothelial cells (HHMEC). Cardiac myocytes and endothelial cells were stimulated with interleukin-1β (IL)-1β (200 U/ml) and treated with levosimendan (0.1–10 μM) for 2–48 hours. IL-1β strongly induced expression of IL-6 and IL-8 in HACM and E-selectin and intercellular adhesion molecule-1 (ICAM-1) in HHMEC and human umbilical vein endothelial cells (HUVEC). Treatment with levosimendan strongly attenuated IL-1β-induced expression of IL-6 and IL-8 in HACM as well as E-selectin and ICAM-1 in ECs. Levosimendan treatment further reduced adhesion of PMN to activated endothelial cells under both static and flow conditions by approximately 50 %. Incubation with 5-hydroxydecanoic acid, a selective blocker of mitochondrial ATP-dependent potassium channels, partly abolished the above seen anti-inflammatory effects. Additionally, levosimendan strongly diminished IL-1β-induced reactive oxygen species and nuclear factor-κB (NF-κB) activity through inhibition of S536 phosphorylation. In conclusion, levosimendan exhibits anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro. These findings could explain, at least in part, the beneficial effects of levosimendan after myocardial infarction.</jats:p>