Levosimendan exerts anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro.
Konstantin A Krychtiuk, Lukas Watzke, Christoph Kaun, Elisabeth Buchberger, Renate Hofer-Warbinek, Svitlana Demyanets, Julia Pisoni, Stefan P Kastl, Sabine Rauscher, Marion Gröger, Arezu Aliabadi, Andreas Zuckermann, Gerald Maurer, Rainer de Martin, Kurt Huber, Johann Wojta, Walter S Speidl
Index: Thromb. Haemost. 113(2) , 350-62, (2015)
Full Text: HTML
Abstract
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.
Related Compounds
Related Articles:
2014-06-05
[Int. J. Pharm. 467(1-2) , 90-9, (2014)]
2014-01-01
[Am. J. Rhinol. Allergy 28(5) , 361-5, (2014)]
2014-07-01
[Ann. Biomed. Eng. 42(7) , 1381-90, (2014)]
Isothiocyanate analogs targeting CD44 receptor as an effective strategy against colon cancer.
2014-07-01
[Med. Chem. Res. 23(8) , 3836-3851, (2014)]
Autophagic dysregulation in glaucomatous trabecular meshwork cells.
2015-03-01
[Biochim. Biophys. Acta 1852(3) , 379-85, (2015)]