Lipoprotein Size and Atherosclerosis Susceptibility in <b> <i>Apoe</i> </b> ^−/− and <b> <i>Ldlr</i> </b> ^−/− Mice

• Murielle M. Véniant

  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.

• Shannon Withycombe

  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.

• 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.

抄録

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 (≈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.

収録刊行物

• Arteriosclerosis, Thrombosis, and Vascular Biology

  Arteriosclerosis, Thrombosis, and Vascular Biology 21 (10), 1567-1570, 2001-10

  Ovid Technologies (Wolters Kluwer Health)

キーワード

• Cardiology and Cardiovascular Medicine

詳細情報

• CRID: 1362544420106881152
• NII論文ID: 30029759000
• DOI: 10.1161/hq1001.097780
• ISSN: 15244636
• ISSN: 10795642
• Web Site: https://www.ahajournals.org/doi/full/10.1161/hq1001.097780
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