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

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.