Macrophage scavenger receptor (SR-A I/II) deficiency reduced diet-induced atherosclerosis in C57BL/6J mice.
The effects of SR-A I/II deficiency and a synthetic anti-oxidant BO-653 on a diet-induced atherosclerosis in C57BL/6J, an inbred strain known to be susceptible to diet-induced atherosclerotic lesion formation, were examined. Quantitative analysis of the extent of atherosclerotic lesions in the mice fed the high-fat diet revealed that the atherosclerotic lesion area in SR-A I/II mutants was significantly reduced by 70% compared to wild type mice. A similar level of lesion reduction (75%) was found in wild type mice fed the high-fat diet supplemented with 0.6% BO-653 compared to those without BO-653. Thus, for C57BL/6J in the setting of prolonged exposure to a high-fat diet, defect of SR-A I/II expression is significantly protective against the development of atherosclerosis, as is the synthetic anti-oxidant BO-653. These results indicate that SR-A I/II has a crucial role in atherosclerotic lesion formation with uptake of oxidized-LDL in this mouse model.
Kamada
N
N
Pharmaceutical Technology Laboratory, Chugai Pharmaceutical Co., Ltd., Shizuoka, Japan.
Kodama
T
T
Suzuki
H
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001161:Arteriosclerosis / Q000188:drug therapy / Q000503:physiopathology*; D001572:Benzofurans / Q000494:pharmacology; D018955:CD36 Antigens / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004032:Diet; D005260:Female; D008077:Lipoproteins, LDL / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009154:Mutation; D051117:Scavenger Receptors, Class A
C106512:2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran; D000975:Antioxidants; D001572:Benzofurans; D018955:CD36 Antigens; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; C495140:Msr1 protein, mouse; D051117:Scavenger Receptors, Class A; D002784:Cholesterol