Anti-inflammatory properties of simvastatin on leukocyte-endothelial cell interactions following hemorrhagic shock
| Autor: | Manfred Dahm, J. Meyer, Joachim Makowski, H. Oelert, Michael Buerke, Diethard Pruefer, S. Guth, Harald Darius, Eckhard Mayer |
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| Rok vydání: | 2002 |
| Předmět: |
Endothelium
P-selectin business.industry Leukocyte Rolling Emergency Nursing Pharmacology Critical Care and Intensive Care Medicine Microcirculation Endothelial stem cell Thrombin medicine.anatomical_structure Simvastatin Immunology Emergency Medicine medicine lipids (amino acids peptides and proteins) business Intravital microscopy medicine.drug |
| Zdroj: | Intensivmedizin und Notfallmedizin. 39:668-676 |
| ISSN: | 1435-1420 0175-3851 |
| DOI: | 10.1007/s00390-002-0309-4 |
| Popis: | Background Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to lower serum cholesterol levels. Recent studies reported that statins have vasculoprotective effects independent of their cholesterol-lowering properties. We studied simvastatin for its ability to modulate leukocyte-endothelial cell interactions under acute inflammation following hemorrhage and reperfusion. Methods The effects of simvastatin on leukocyte-endothelial cell interactions were observed by intravital microscopy in the rat mesenteric microcirculation and by immunohistochemical analyzes. Simvastatin (50 μg/kg or 100 μg/kg) was administrated intraperitoneally 18 h before study. Inflammatory effects (i.e., leukocyte rolling, firm adherence, and transmigration) were studied after mesenteric superfusion with thrombin (0.5U/ml) or after hemorrhage (60min) and reperfusion (90min). Results Simvastatin treatment significantly and dose dependently attenuated leukocyte rolling, adherence and transmigration in the rat mesenteric microcirculation superfused by thrombin or hemorrhage followed by reperfusion. Immunohistochemical detection of endothelial cell adhesion molecule P-selectin showed a 60% decrease in endothelial cell surface expression within the intestine. Conclusions These data provide evidence that simvastatin is a potent and effective vasculoprotective compound that inhibits leukocyte-endothelial cell interactions after ischemia and reperfusion. Thus, HMG-CoA reductase inhibitors like simvastatin seem to have important anti-inflammatory effects besides their well-known lipid-lowering actions. |
| Databáze: | OpenAIRE |
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