极低密度脂蛋白
内科学
内分泌学
载脂蛋白B
基因亚型
载脂蛋白E
胆固醇
低密度脂蛋白受体
脂蛋白
内生
受体
生物
化学
医学
生物化学
基因
疾病
作者
Christopher W. Knouff,Myron E. Hinsdale,Hafid Mezdour,Michael K. Altenburg,Masahiko Watanabe,Steven H. Quarfordt,Patrick M. Sullivan,Nobuyo Maeda
摘要
We have generated mice expressing the human apo E4 isoform in place of the endogenous murine apo E protein and have compared them with mice expressing the human apo E3 isoform. Plasma lipid and apolipoprotein levels in the mice expressing only the apo E4 isoform (4/4) did not differ significantly from those in mice with the apo E3 isoform (3/3) on chow and were equally elevated in response to increased lipid and cholesterol in their diet. However, on all diets tested, the 4/4 mice had approximately twice the amount of cholesterol, apo E, and apo B-48 in their VLDL as did 3/3 mice. The 4/4 VLDL competed with human LDL for binding to the human LDL receptor slightly better than 3/3 VLDL, but the VLDL clearance rate in 4/4 mice was half that in 3/3 mice. On an atherogenic diet, there was a trend toward greater atherosclerotic plaque size in 4/4 mice compared with 3/3 mice. These data, together with our earlier observations in wild-type and human APOE*2-replacement mice, demonstrate a direct and highly significant correlation between VLDL clearance rate and mean atherosclerotic plaque size. Therefore, differences solely in apo E protein structure are sufficient to cause alterations in VLDL residence time and atherosclerosis risk in mice.
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