Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice.
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.
Febbraio
M
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. mjfebbra@med.cornell.edu
Podrez
E A
EA
Smith
J D
JD
Hajjar
D P
DP
Hazen
S L
SL
Hoff
H F
HF
Sharma
K
K
Silverstein
R L
RL
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
D001057:Apolipoproteins E; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D002784:Cholesterol