Reduced atherosclerotic lesions in mice deficient for total or macrophage-specific expression of scavenger receptor-A

Vladimir R. Babaev, Linda A. Gleaves, Kathy J. Carter, Hiroshi Suzuki, Tatsuhiko Kodama, Sergio Fazio, MacRae F. Linton

    Research output: Contribution to journalArticle

    137 Scopus citations

    Abstract

    The absence of the scavenger receptor A (SR-A)-I/II has produced variable effects on atherosclerosis in different murine models. Therefore, we examined whether SR-AI/II deficiency affected atherogenesis in C57BL/6 mice, an inbred strain known to be susceptible to diet-induced atherosclerotic lesion formation, and whether the deletion of macrophage SR-AI/II expression would modulate lesion growth in C57BL/6 mice and LDL receptor (LDLR)(-/-) mice. SR-AI/II-deficient (SR-AI/II(-/-)) female and male mice on the C57BL/6 background were challenged with a butterfat diet for 30 weeks. No differences were detected in plasma lipids between SR-AI/II(-/-) and SR-AI/II(+/+) mice, whereas both female and male SR-AI/II(-/-) mice had a tremendous reduction (81% to 86%) in lesion area of the proximal aorta compared with SR-AI/II(+/+) mice. Next, to analyze the effect of macrophage-specific SR-AI/II deficiency in atherogenesis, female C57BL/6 mice were lethally irradiated, transplanted with SR-AI/II(-/-) or SR-AI/II(+/+) fetal liver cells, and challenged with the butterfat diet for 16 weeks. In a separate experiment, male LDLR(-/-) mice were reconstituted with SR-AI/II(-/-) or SR-AI/II(+/+) fetal liver cells and challenged with a Western diet for 10 weeks. No significant differences in plasma lipids and lipoprotein profiles were noted between the control and experimental groups in either experiment. SR-AI/II(-/-)→C57BL/6 mice, however, had a 60% reduction in lesion area of the proximal aorta compared with SR-AI/II(+/+)→C57BL/6 mice. A similar level of reduction (60%) in lesion area was noted in the proximal aorta and the entire aorta en face of SR-AI/II(-/-)→LDLR(-/-) mice compared with SR-AI/II(+/+)→LDLR(-/-) mice. These results demonstrate in vivo that SR-AI/II expression has no impact on plasma lipid levels and that macrophage SR-AI/II contributes significantly to atherosclerotic lesion formation.

    Original languageEnglish (US)
    Pages (from-to)2593-2599
    Number of pages7
    JournalArteriosclerosis, thrombosis, and vascular biology
    Volume20
    Issue number12
    DOIs
    StatePublished - Jan 1 2000

    Keywords

    • Atherosclerosis
    • Fetal liver cell transplantation
    • Foam cells formation
    • Macrophages
    • Scavenger receptor type A

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

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