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

135 Citations (Scopus)

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
StatePublished - 2000
Externally publishedYes

Fingerprint

Scavenger Receptors
Inbred C57BL Mouse
Macrophages
LDL Receptors
Aorta
Class A Scavenger Receptors
Atherosclerosis
Diet
Lipids
Inbred Strains Mice
Liver
Lipoproteins
Control Groups
Growth

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Reduced atherosclerotic lesions in mice deficient for total or macrophage-specific expression of scavenger receptor-A. / Babaev, Vladimir R.; Gleaves, Linda A.; Carter, Kathy J.; Suzuki, Hiroshi; Kodama, Tatsuhiko; Fazio, Sergio; Linton, MacRae F.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 20, No. 12, 2000, p. 2593-2599.

Research output: Contribution to journalArticle

Babaev, Vladimir R. ; Gleaves, Linda A. ; Carter, Kathy J. ; Suzuki, Hiroshi ; Kodama, Tatsuhiko ; Fazio, Sergio ; Linton, MacRae F. / Reduced atherosclerotic lesions in mice deficient for total or macrophage-specific expression of scavenger receptor-A. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2000 ; Vol. 20, No. 12. pp. 2593-2599.
@article{932e6bf591a44462bf3ce85f6a670e6d,
title = "Reduced atherosclerotic lesions in mice deficient for total or macrophage-specific expression of scavenger receptor-A",
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.",
keywords = "Atherosclerosis, Fetal liver cell transplantation, Foam cells formation, Macrophages, Scavenger receptor type A",
author = "Babaev, {Vladimir R.} and Gleaves, {Linda A.} and Carter, {Kathy J.} and Hiroshi Suzuki and Tatsuhiko Kodama and Sergio Fazio and Linton, {MacRae F.}",
year = "2000",
language = "English (US)",
volume = "20",
pages = "2593--2599",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "12",

}

TY - JOUR

T1 - Reduced atherosclerotic lesions in mice deficient for total or macrophage-specific expression of scavenger receptor-A

AU - Babaev, Vladimir R.

AU - Gleaves, Linda A.

AU - Carter, Kathy J.

AU - Suzuki, Hiroshi

AU - Kodama, Tatsuhiko

AU - Fazio, Sergio

AU - Linton, MacRae F.

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - Atherosclerosis

KW - Fetal liver cell transplantation

KW - Foam cells formation

KW - Macrophages

KW - Scavenger receptor type A

UR - http://www.scopus.com/inward/record.url?scp=0033675698&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033675698&partnerID=8YFLogxK

M3 - Article

VL - 20

SP - 2593

EP - 2599

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 12

ER -