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. J Atheroscler Thromb, 2010; 17:796-804.