© 2000 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Reduced Atherosclerotic Lesions in Mice Deficient for Total or Macrophage-Specific Expression of Scavenger Receptor-A
From the Departments of Medicine (V.R.B., L.A.G., K.J.C., S.F., M.F.L.), Pathology (S.F.), and Pharmacology (M.F.L.), Vanderbilt University Medical Center, Nashville, Tenn; and Department of Molecular Biology and Medicine (H.S., T.K.), University of Tokyo, Tokyo, Japan.
Correspondence to Dr MacRae Linton or Dr Sergio Fazio, Department of Cardiovascular Medicine, Vanderbilt University School of Medicine, 315 Medical Research Building II, Nashville, TN 37232-6300. E-mail macrae.linton (or sergio.fazio){at}mcmail.vanderbilt.edu
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.
Key Words: atherosclerosis • macrophages • scavenger receptor type A • foam cells formation • fetal liver cell transplantation
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