MDOC™ and atorvastatin have potential antiinflammatory effects in vascular endothelium of apoE −/− mouse model of atherosclerosis

• Published in: Life sciences (1973) 2006-03, Vol.78 (17), p.1983-1989
• Main Authors: Nachtigal, Petr, Pospisilova, Nada, Pospechova, Katerina, Jamborova, Gabriela, Kopecky, Martin, Jaynes, Robert, Briestensky, Jiri, Santar, Ivan, Smahelova, Alena, Solichova, Dagmar, Zdansky, Petr, Semecky, Vladimir
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; Atherosclerosis; Atherosclerosis - drug therapy; Atorvastatin; Atorvastatin Calcium; Cell adhesion molecules; Cellulose, Oxidized - pharmacology; Cellulose, Oxidized - therapeutic use; Diet; Disease Models, Animal; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Endothelium, Vascular - pathology; Heptanoic Acids - pharmacology; Heptanoic Acids - therapeutic use; Hyperlipidemias - drug therapy; Intercellular Adhesion Molecule-1 - metabolism; Lipoproteins - blood; Male; MDOC; Mice; Mice, Knockout; Pyrroles - pharmacology; Pyrroles - therapeutic use; Simvastatin; Simvastatin - pharmacology; Triglycerides - blood; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2005.08.041

Members of the immunoglobulin superfamily of endothelial adhesion molecules, vascular cell adhesion molecule (VCAM-1) and intercellular cell adhesion molecule (ICAM- 1), strongly participate in leukocyte adhesion to the endothelium and play an important role in all stages of atherogenesis. The aim of this study was to detect and quantify the changes of endothelial expression of VCAM-1, and ICAM-1 in the vessel wall after the short-term administration of simvastatin, atorvastatin, and micro dispersed derivatives of oxidised cellulose (MDOC™) in apolipoprotein-E-deficient (apoE −/−) mice atherosclerotic model. Hyperlipidemic apoE −/− mice ( n = 32) received normal chow diet or diet containing simvastatin or atorvastatin 10 mg/kg/day or MDOC™ 50 mg/kg/day. Total cholesterol, VLDL, LDL, HDL and TAG were measured and the endothelial expression of VCAM-1 and ICAM-1 was visualized and quantified by means of immunohistochemistry and stereology, respectively. Total cholesterol levels was insignificantly lowered only in MDOC™ treated mice but not in mice treated with statins. ICAM-1 endothelial expression was not affected by neither simvastatin nor MDOC™ treatment. However, significant diminution of VCAM-1 endothelial expression was observed in both atorvastatin and MDOC™ treated mice. These results provide new information of potential hypolipidemic substance MDOC™ and its potential anti-inflammatory effects. Furthermore, we have confirmed anti-inflammatory effects of atorvastatin independent of plasma cholesterol lowering. Thus, the results of this study show potential benefit of both MDOC™ and atorvastatin treatment in apoE −/− mouse model of atherosclerosis suggesting their possible combination might be of interest.