title: The effect of AVE 0991, nebivolol and doxycycline on inflammatory mediators in an apoE-knockout mouse model of atherosclerosis.
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).
  
  
  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.
authors.affiliation: Jagiellonian University School of Medicine, Cracow, Poland. mmjawien@cyf-kr.edu.pl
authors.forename: Jacek
authors.initials: J
authors.lastname: Jawien
authors.forename: Justyna
authors.initials: J
authors.lastname: Toton-Zuranska
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kus
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Pawlowska
authors.forename: Rafal
authors.initials: R
authors.lastname: Olszanecki
authors.forename: Ryszard
authors.initials: R
authors.lastname: Korbut
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood* / Q000188:drug therapy*; D001578:Benzopyrans / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004318:Doxycycline / Q000627:therapeutic use*; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D007093:Imidazoles / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000068577:Nebivolol
chemical_list: C469726:AVE 0991; D001057:Apolipoproteins E; D001578:Benzopyrans; D004983:Ethanolamines; D007093:Imidazoles; D018836:Inflammation Mediators; D000068577:Nebivolol; D004318:Doxycycline