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J Atheroscler Thromb ; 17(8): 796-804, 2010 Aug 31.
Article in English | MEDLINE | ID: mdl-20379054

ABSTRACT

AIM: 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. CONCLUSION: 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.


Subject(s)
Aorta, Abdominal/pathology , Aorta, Thoracic/pathology , Apolipoproteins E/physiology , Atherosclerosis/prevention & control , Cholesterol, Dietary/administration & dosage , Metagenome , Animals , Aorta, Abdominal/metabolism , Aorta, Thoracic/metabolism , Atherosclerosis/etiology , Atherosclerosis/metabolism , Blotting, Western , Cholesterol/blood , Disease Models, Animal , Female , Germ-Free Life , Intestinal Mucosa/microbiology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction
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