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28 September 2012

The effect of AVE 0991, nebivolol and doxycycline on inflammatory mediators in an apoE-knockout mouse model of atherosclerosis

Jacek JawienABCDEFG, Justyna Toton-ZuranskaBCD, Katarzyna KusBCD, Malgorzata PawlowskaBCD, Rafal OlszaneckiAD, Ryszard KorbutADE

DOI: 10.12659/MSM.883478

Med Sci Monit 2012; 18(10): BR389-393

Abstract

Background: The aim of this study was to investigate whether the 3 different substances that can decrease the development of atherosclerosis – nebivolol, AVE 0991 and doxycycline – could at the same time diminish the level of inflammatory indicators interleukin-6 (IL-6), interleukin-12 (IL-12), serum amyloid A (SAA), and monocyte chemotactic protein-1 (MCP-1). Material/Methods: Forty 8-week-old female apoE–knockout mice on the C57BL/6J background were divided into 4 groups and put on chow diet for 4 months. Three experimental groups received the same diet as a control group, mixed with AVE 0991 at a dose 0.58 µmol per kg of body weight per day, nebivolol at a dose 2.0 µmol per kg of body weight per day, and doxycycline at a dose 1.5 mg per kg of body weight per day. At the age of 6 months, the mice were sacrificed. Results: All inflammatory indicators (MCP-1, IL-6, IL-12 and SAA) were diminished by AVE 0991. There was also a tendency to lower MCP-1, IL-6, IL-12 and SAA levels by nebivolol and doxycycline; however, it did not reach statistical significance. Conclusions: Of the 3 presented substances, only AVE 0991 was able to diminish the rise of inflammatory markers. Therefore, drug manipulations in the renin-angiotensin-aldosterone axis seem to be the most promising in the future treatment of atherogenesis.

Keywords: Inflammation Mediators - blood, Imidazoles - therapeutic use, Ethanolamines - therapeutic use, Doxycycline - therapeutic use, Benzopyrans - therapeutic use, Atherosclerosis - drug therapy, Apolipoproteins E - metabolism, Mice, Knockout

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750