title: Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice.
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.
authors.affiliation: 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. mjfebbra@med.cornell.edu
authors.forename: M
authors.initials: M
authors.lastname: Febbraio
authors.forename: E A
authors.initials: EA
authors.lastname: Podrez
authors.forename: J D
authors.initials: JD
authors.lastname: Smith
authors.forename: D P
authors.initials: DP
authors.lastname: Hajjar
authors.forename: S L
authors.initials: SL
authors.lastname: Hazen
authors.forename: H F
authors.initials: HF
authors.lastname: Hoff
authors.forename: K
authors.initials: K
authors.lastname: Sharma
authors.forename: R L
authors.initials: RL
authors.lastname: Silverstein
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000502:physiology; D001161:Arteriosclerosis / Q000209:etiology / Q000517:prevention & control*; D018955:CD36 Antigens / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D005260:Female; D008077:Lipoproteins, LDL / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D051116:Receptors, Scavenger; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain
chemical_list: D001057:Apolipoproteins E; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D002784:Cholesterol