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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1567.)
© 2001 American Heart Association, Inc.

Brief Review

Lipoprotein Size and Atherosclerosis Susceptibility in Apoe^-/- and Ldlr^-/- Mice

Murielle M. Véniant; Shannon Withycombe; Stephen G. Young

From Amgen Inc (M.M.V.), Thousand Oaks, Calif; the Gladstone Institute of Cardiovascular Disease (S.W., S.G.Y.), University of California, San Francisco; the Cardiovascular Research Institute (S.G.Y.), University of California, San Francisco; and the Department of Medicine (S.G.Y.), University of California, San Francisco, and the Medical Service (S.G.Y.), San Francisco General Hospital, San Francisco, Calif.

Correspondence to Stephen G. Young, MD, or Murielle Véniant, PhD, Gladstone Institute of Cardiovascular Disease, PO Box 419100, San Francisco, CA 94141-9100. E-mail syoung{at}gladstone.ucsf.edu or mveniant@amgen.com

Abstract—— 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 Apob¹⁰⁰ (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 (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.

Key Words: atherosclerosis • apolipoprotein B • LDL receptor • Cre recombinase • microsomal triglyceride transfer protein

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