Comparative reactivity of remnant-like lipoprotein particles (RLP) and low-density lipoprotein (LDL) to LDL receptor and VLDL receptor: effect of a high-dose statin on VLDL receptor expression
Comparative reactivity of remnant-like lipoprotein particles (RLP) and low-density lipoprotein (LDL) to LDL receptor and VLDL receptor: effect of a high-dose statin on VLDL receptor expression
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残留样脂蛋白颗粒（RLP）和低密度脂蛋白（LDL）对LDL受体和VLDL受体的比较反应性：高剂量他汀类药物对VLDL受体表达的影响
DOI：
10.1016/j.cca.2011.10.033
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发表时间：
2012
期刊：
影响因子：
5
通讯作者：
Imagawa M
中科院分区：
文献类型：
--
作者：
Mabuchi H;Nohara A;Imagawa M
方法采用LDL受体和VLDL受体转染的ldlA-7、HepG 2和L 6细胞，观察了LDL受体和VLDL受体对残粒样脂蛋白颗粒（RLP）和LDL颗粒的反应性的影响。用超离心法分离人LDL和兔β-VLDL。使用免疫亲和混合凝胶分离人RLP。观察他汀类药物对脂蛋白受体的影响，发现LDL受体和VLDL受体均识别RLP。在LDL受体转染子中，RLP、β-VLDL和LDL均与LDL受体结合。冷RLP与DiI-β-VLDL有效竞争;然而，冷LDL竞争较弱。在VLDL受体转染子中，RLP和β-VLDL与VLDL受体结合，而LDL不与之结合。RLP中载脂蛋白E含量较高，与VLDL受体的结合亲和力高于β-VLDL。低浓度他汀类药物诱导HepG 2细胞LDL受体表达，而高浓度他汀类药物诱导L 6成肌细胞VLDL受体表达。结论SRLP与肝LDL受体的结合效率高于LDL，这可能解释了他汀类药物主要通过降低血浆RLP而不是通过降低LDL来预防心血管风险的机制。此外，高剂量他汀类药物也可能通过肌肉VLDL受体降低血浆RLP。
BACKGROUNDComparison of the reactivity of remnant-like lipoprotein particles (RLP) and LDL particles to LDL receptor and VLDL receptor has not been investigated.METHODSLDL receptor- or VLDL receptor-transfected ldlA-7, HepG2 and L6 cells were used. Human LDL and rabbit β-VLDL were isolated by ultracentrifugation. Human RLP was isolated using an immunoaffinity mixed gel. The effect of statin on lipoprotein receptors was examined.RESULTSBoth LDL receptor and VLDL receptor recognized RLP. In LDL receptor transfectants, RLP, β-VLDL and LDL all bound to LDL receptor. Cold RLP competed efficiently with DiI-β-VLDL; however, cold LDL competed weakly. In VLDL receptor transfectants, RLP and β-VLDL bound to VLDL receptor, but not LDL. RLP bound to VLDL receptor with higher affinity than β-VLDL because of higher apolipoprotein E in RLP. LDL receptor expression was induced in HepG2 by the low concentration of statin while VLDL receptor expression was induced in L6 myoblasts at higher concentration.CONCLUSIONSRLP are bound to hepatic LDL receptor more efficiently than LDL, which may explain the mechanism by which statins prevent cardiovascular risk by primarily reducing plasma RLP rather than by reducing LDL. Additionally, a high-dose of statins also may reduce plasma RLP through muscular VLDL receptor.