Lipoprotein clearance mechanisms in LDL receptor-deficient "Apo-B48-only" and '"Apo-B100-only" mice
Lipoprotein clearance mechanisms in LDL receptor-deficient "Apo-B48-only" and '"Apo-B100-only" mice
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DOI：
10.1172/jci4164
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发表时间：
1998-10-15
影响因子：
15.9
通讯作者：
Young, SG
中科院分区：
文献类型：
--
作者：
Véniant, MM;Zlot, CH;Young, SG
低密度脂蛋白受体（LDLR）在清除含载脂蛋白B48的脂蛋白中的作用以及LDLR相关蛋白（LRP）在清除含载脂蛋白B100的脂蛋白中的作用尚未明确。为了解决这些问题，我们对“apo-B48-only”等位基因、“apo-B100-only”等位基因或野生型apo-B等位基因（分别为Ldlr（-/-）Apob（48/48）、Ldlr（-/-）Apob（100/100）和Ldlr（-/-）Apob（+/+））纯合的LDL受体缺陷小鼠进行了表征。Ldlr（-/-）Apob（48/48）小鼠的血浆apo-B48和LDL胆固醇水平高于Apob（48/48）小鼠，表明LDL受体在清除含apo-B48的脂蛋白中起重要作用。为了检测LRP在含apo-B100脂蛋白清除中的作用，我们通过腺病毒介导的受体相关蛋白（RAP）表达阻断Ldlr（-/-）Apob（100/100）小鼠的肝脏LRP功能。RAP表达没有改变Ldlr（-/-）Apob（100/100）小鼠的apo-B100水平。相反，RAP表达引起Apob（48/48）和Ldlr（-/-）Apob（48/48）小鼠血浆apo-B48水平的显著增加。这些数据表明，LRP是重要的清除载脂蛋白B48-含有脂蛋白，但在清除载脂蛋白B100-含有脂蛋白没有显着的作用。
The role of the low density lipoprotein receptor (LDLR) in the clearance of apo-B48-containing lipoproteins and the role of the LDLR-related protein (LRP) in the removal of apo-B100-containing lipoproteins have not been clearly defined. To address these issues, we characterized LDLR-deficient mice homozygous for an "apo-B48-only" allele, an "apo-B100-only" allele, or a wild-type apo-B allele (Ldlr(-/-)Apob(48/48), Ldlr(-/-)Apob(100/100), and Ldlr(-/-)Apob(+/+), respectively). The plasma apo-B48 and LDL cholesterol levels were higher in Ldlr(-/-)Apob(48/48) mice than in Apob(48/48) mice, indicating that the LDL receptor plays a significant role in the removal of apo-B48-containing lipoproteins. To examine the role of the LRP in the clearance of apo-B100-containing lipoproteins, we blocked hepatic LRP function in Ldlr(-/-)Apob(100/100) mice by adenoviral-mediated expression of the receptor-associated protein (RAP). RAP expression did not change apo-B100 levels in Ldlr(-/-)Apob(100/100) mice. In contrast, RAP expression caused a striking increase in plasma apo-B48 levels in Apob(48/48) and Ldlr(-/-)Apob(48/48) mice. These data imply that LRP is important for the clearance of apo-B48-containing lipoproteins but plays no significant role in the clearance of apo-B100-containing lipoproteins.