Oxidized cholesterol in the diet accelerates the development of atherosclerosis in LDL receptor- and apolipoprotein E-deficient mice.
The aim of the current study was to determine whether oxidized cholesterol in the diet accelerates atherosclerosis in low density lipoprotein receptor- (LDLR) and apolipoprotein E- (apo E) deficient mice. Mice were fed either a control diet or a diet containing oxidized cholesterol. For LDLR-deficient mice, the control diet consisted of regular mouse chow to which 1.0% cholesterol was added. The oxidized diet was identical to the control diet except that 5% of the added cholesterol was oxidized. In apo E-deficient mice, the control diet contained 0.15% cholesterol, whereas in the oxidized diet, 5% of the added cholesterol was oxidized. LDLR-deficient and apo E-deficient mice were fed the experimental diets for 7 and 4 months, respectively. In mice fed the oxidized-cholesterol diets, the levels of oxidized cholesterol in sera were increased. At the end of the experiment, aortas were removed and atherosclerosis was assessed. We found that in LDLR-deficient mice, feeding of an oxidized-cholesterol diet resulted in a 32% increase in fatty streak lesions (15.93+/-1.59% versus 21.00+/-1.38%, P<0.03). Similarly, in apo E-deficient mice, feeding of an oxidized-cholesterol diet increased fatty streak lesions by 38% (15.01+/-0.92% versus 20. 70+/-0.86%, P<0.001). The results of the current study thus demonstrate that oxidized cholesterol in the diet accelerates fatty streak lesion formation in both LDLR- and apo E-deficient mice.
Staprans
I
I
Department of Veterans Affairs Medical Center, University of California, San Francisco 94121, USA. stapan@itsa.ucsf.edu
Pan
X M
XM
Rapp
J H
JH
Grunfeld
C
C
Feingold
K R
KR
D000818:Animals; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000097:blood / Q000235:genetics* / Q000473:pathology; D001835:Body Weight; D008076:Cholesterol, HDL / Q000097:blood; D003327:Coronary Disease / Q000097:blood / Q000235:genetics; D004036:Diet, Atherogenic; D005260:Female; D015227:Lipid Peroxidation / Q000502:physiology; D008077:Lipoproteins, LDL / Q000097:blood / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010545:Peroxides / Q000097:blood; D011973:Receptors, LDL / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; D010545:Peroxides; D011973:Receptors, LDL; D014280:Triglycerides; C099252:oxidized low density lipoprotein