Lipoprotein size and atherosclerosis susceptibility in Apoe(-/-) and Ldlr(-/-) mice.
Two hypercholesterolemic mouse models, the apo-E-deficient mouse (Apoe(-/-)) and the LDL receptor-deficient mouse (Ldlr(-/-)), have been used extensively as animal models of atherogenesis. Total plasma cholesterol levels in chow-fed Apoe(-/-) mice are much higher than in Ldlr(-/-) mice. In a recent study, we managed to even-up the cholesterol levels in Apoe(-/-) mice and Ldlr(-/-) mice by making both models homozygous for the Apob(100) (apo B-100-only) allele. On a chow diet, apo-E-deficient apo B-100-only mice (Apoe(-/-)Apob(100/100)) and LDL receptor-deficient apo B-100-only mice (Ldlr(-/-)Apob(100/100)) had similar total plasma cholesterol levels ( approximately 300 mg/dL). The plasma of Ldlr(-/-)Apob(100/100) mice contained large numbers of small lipoproteins, whereas the plasma of Apoe(-/-)Apob(100/100) mice contained much lower levels of much larger lipoproteins. Interestingly, the Ldlr(-/-)Apob(100/100) mice developed far more extensive atherosclerotic lesions than the Apoe(-/-)Apob(100/100) mice. The finding of substantially more atherosclerosis in Ldlr(-/-)Apob(100/100) mice than in Apoe(-/-)Apob(100/100) mice, despite nearly identical cholesterol levels, suggests that large numbers of small apo B-100-containing lipoproteins are far more atherogenic than lower numbers of large apo B-100-containing lipoproteins.
Véniant
M M
MM
Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94141-9100, USA. mveniant@amgen.com
Withycombe
S
S
Young
S G
SG
D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D006720:Homozygote; D008074:Lipoproteins / Q000737:chemistry*; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics*
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008074:Lipoproteins; D011973:Receptors, LDL; D002784:Cholesterol