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PMID: 10772649 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice.

The Journal of clinical investigation ·Vol. 105 ·No. 8 ·2000-04-00 ·Pages 1049-56

Febbraio M, Podrez EA, Smith JD, Hajjar DP, Hazen SL, Hoff HF, Sharma K, Silverstein RL

Abstract

Macrophage scavenger receptors have been implicated as key players in the pathogenesis of atherosclerosis. To assess the role of the class B scavenger receptor CD36 in atherogenesis, we crossed a CD36-null strain with the atherogenic apo E-null strain and quantified lesion development. There was a 76.5% decrease in aortic tree lesion area (Western diet) and a 45% decrease in aortic sinus lesion area (normal chow) in the CD36-apo E double-null mice when compared with controls, despite alterations in lipoprotein profiles that often correlate with increased atherogenicity. Macrophages derived from CD36-apo E double-null mice bound and internalized more than 60% less copper-oxidized LDL and LDL modified by monocyte-generated reactive nitrogen species. A similar inhibition of in vitro lipid accumulation and foam cell formation after exposure to these ligands was seen. These results support a major role for CD36 in atherosclerotic lesion development in vivo and suggest that blockade of CD36 can be protective even in more extreme proatherogenic circumstances.

MeSH Terms
Animals Apolipoproteins E/genetics,physiology Arteriosclerosis/etiology,prevention & control CD36 Antigens/genetics,physiology Cells, Cultured Cholesterol/blood Female Lipoproteins, LDL/metabolism Macrophages, Peritoneal/cytology Male Mice Mice, Inbred C57BL Receptors, Immunologic/antagonists & inhibitors,genetics,physiology Receptors, Scavenger Triglycerides/blood Weight Gain
Chemicals
Apolipoproteins E CD36 Antigens Lipoproteins, LDL Receptors, Immunologic Receptors, Scavenger Triglycerides oxidized low density lipoprotein Cholesterol
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Febbraio M
Department of Medicine, Division of Hematology and Medical Oncology, Center of Vascular Biology, Weill Medical College of Cornell University, New York, New York 10021, USA. [email protected]
Podrez E A
Smith J D
Hajjar D P
Hazen S L
Hoff H F
Sharma K
Silverstein R L
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI9259
Email
[email protected]
Published
2000-04-00
Pages
1049-56
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC300837
Subset
IM
Grants
NHLBI NIH HHS · HL-42540 · United States
NHLBI NIH HHS · HL-56987 · United States
NHLBI NIH HHS · HL-62526 · United States
Corrections
CommentIn
PMID: 10772646
CommentIn
PMID: 10974014
External Links
PubMed source DOI: 10.1172/JCI9259 PMC Full Text View journal details
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