title: Absence of microbiota (germ-free conditions) accelerates the atherosclerosis in ApoE-deficient mice fed standard low cholesterol diet.
abstract: OBJECTIVE
  The aim of our work was to determine the influence of intestinal bacteria on the development of atherosclerotic lesions using apolipoprotein E (ApoE)-deficient knockout mice.
  
  
  METHODS
  The experiments were performed on ApoE-/--deficient mouse strain C57BL/6, bred under germ-free (GF) conditions for two generations or under conventional conditions with defined microflora (CV). The mice were fed a standard low cholesterol diet or cholesterol-rich diet for 3-4 months. We studied the development of advanced lesions in the thoracic and abdominal aorta by histological, morphometric and immunohistological methods.
  
  
  RESULTS
  Conventionally reared ApoE-/- mice (containing no pathogenic intestinal microbiota) and fed a standard low cholesterol diet in contrast to a high cholesterol diet did not develop atherosclerotic aortic plaques. In contrast, ApoE-/- mice reared under germfree conditions for 2 generations and fed a low cholesterol diet exhibited atherosclerotic plaques in the aorta. Characteristic lipid deposition with foam cells and macrophages was found in their arterial walls.
  
  
  CONCLUSIONS
  In contrast to the absence of atherosclerotic plaques in conventionally reared ApoE-deficient mice, germ-free ApoE-/- mice consuming the same low cholesterol standard diet developed atherosclerotic plaques in the aorta. Differences in atherosclerotic plaques between GF and CV ApoE-/- mice are not so apparent when mice are fed a high cholesterol diet. Our findings thus document the protective effect of microbiota (commensal bacteria) on atherosclerosis development.
authors.affiliation: Department of Immunology and Gnotobiology, Institute of Microbiology, vvi, Czech Academy of Sciences, Praque, Czech Republic. stepankova.renata@seznam.cz
authors.forename: Renata
authors.initials: R
authors.lastname: Stepankova
authors.forename: Zbynek
authors.initials: Z
authors.lastname: Tonar
authors.forename: Jirina
authors.initials: J
authors.lastname: Bartova
authors.forename: Lukas
authors.initials: L
authors.lastname: Nedorost
authors.forename: Pavel
authors.initials: P
authors.lastname: Rossman
authors.forename: Rudolf
authors.initials: R
authors.lastname: Poledne
authors.forename: Martin
authors.initials: M
authors.lastname: Schwarzer
authors.forename: Helena
authors.initials: H
authors.lastname: Tlaskalova-Hogenova
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism / Q000473:pathology*; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology*; D001057:Apolipoproteins E / Q000502:physiology*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D015153:Blotting, Western; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D005856:Germ-Free Life; D007413:Intestinal Mucosa / Q000382:microbiology; D008297:Male; D054892:Metagenome; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001057:Apolipoproteins E; D002791:Cholesterol, Dietary; D012333:RNA, Messenger; D002784:Cholesterol