Increased LDL cholesterol and atherosclerosis in LDL receptor-deficient mice with attenuated expression of scavenger receptor B1
Increased LDL cholesterol and atherosclerosis in LDL receptor-deficient mice with attenuated expression of scavenger receptor B1
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DOI：
10.1161/01.atv.20.4.1068
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发表时间：
2000-04-01
影响因子：
8.7
通讯作者：
Tall, AR
中科院分区：
文献类型：
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作者：
Huszar, D;Varban, ML;Tall, AR
清道夫受体BI（SR-BI）是一种多配体的细胞表面受体，在啮齿类动物的高密度脂蛋白稳态中起核心作用。为了研究SR-BI在动脉粥样硬化中的作用，将SR-BI表达减弱的小鼠与低密度脂蛋白（LDL）受体缺陷小鼠杂交。化合物纯合突变体显示血浆胆固醇增加，令人惊讶的是，这主要是由于LDL胆固醇和载脂蛋白B水平增加。低密度脂蛋白周转研究表明，这是由于增加低密度脂蛋白胆固醇的生产，而不是减少。LDL催化剂。与LDL受体缺陷对照组相比，化合物突变雄性小鼠的动脉粥样硬化病变大小显著增加（分别为93 427+/-16 079和34 448+/-5 331 μ m（2）; P=0.003）。SR-BI表达减弱的致动脉粥样硬化作用可能部分是由于LDL胆固醇水平升高。这些发现表明，受体的上调可能具有治疗动脉粥样硬化的治疗潜力，
Scavenger receptor BI (SR-BI) is a multiligand cell-surface receptor that plays a central role in high density lipoprotein homeostasis in rodents. To investigate a role for SR-BI in atherosclerosis, mice with attenuated SR-BI expression were crossed with low density Lipoprotein (LDL) receptor-deficient mice, Compound-homozygous mutants showed increased plasma cholesterol, surprisingly due primarily to increased LDL cholesterol and apolipoprotein B levels. LDL turnover studies showed that this resulted from increased LDL cholesterol production rather than decreased. LDL catabolism. Atherosclerotic lesion size was significantly increased in male compound-mutant mice relative to LDL receptor-deficient controls (93 427+/-16 079 versus 34 448+/-5 331 mu m(2), respectively; P=0.003). The proatherogenic effect of attenuated SR-BI expression may in part be due to increased LDL cholesterol levels. These findings suggest that upregulation of the receptor could have therapeutic potential for the treatment of atherosclerosis,