Lower plasma levels and accelerated clearance of high density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type I transgenic mice
Lower plasma levels and accelerated clearance of high density lipoprotein (HDL) and non-HDL cholesterol in scavenger receptor class B type I transgenic mice
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DOI：
10.1074/jbc.274.11.7165
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发表时间：
1999-03-12
影响因子：
4.8
通讯作者：
Rubin, EM
中科院分区：
文献类型：
--
作者：
Ueda, Y;Royer, L;Rubin, EM
最近的研究表明，清道夫受体B I型（SR-BI）可能在肝脏和类固醇生成组织摄取高密度脂蛋白（HDL）胆固醇酯中起重要作用。为了研究肝脏特异性SR-BI过表达对脂质代谢的体内影响，我们用SR-BI基因组构建体建立了几种SR-BI转基因小鼠品系，其中SR-BI启动子区域已被载脂蛋白（apo）A-I启动子取代。组成性增加SR-BI表达对血浆HDL和非HDL脂蛋白和载脂蛋白的影响进行了表征。有SR-BI的表达和apoA-I和HDL胆固醇水平之间的负相关性，在转基因小鼠喂养的小鼠饲料或高脂肪和高胆固醇的饮食。在SR-BI转基因小鼠中的意外发现是SR-BI转基因对非HDL胆固醇和apoB的显著影响，其水平也与SR-BI表达负相关。与血浆HDL和非HDL胆固醇的降低一致的是，与对照动物相比，转基因动物中HDL、非HDL及其主要相关载脂蛋白的清除加速。SR-BI过表达对血浆脂蛋白影响的这些体内研究支持先前提出的假设，即SR-BI加速HDL的代谢，并且还突出了该受体参与非HDL脂蛋白代谢的能力。
Recent studies have indicated that the scavenger receptor class B type I (SR-BI) may play an important role in the uptake of high density lipoprotein (HDL) cholesteryl ester in liver and steroidogenic tissues. To investigate the in vivo effects of liver-specific SR-BI overexpression on lipid metabolism, we created several lines of SR-BI transgenic mice with an SR-BI genomic construct where the SR-BI promoter region had been replaced by the apolipoprotein (apo)A-I promoter. The effect of constitutively increased SR-BI expression on plasma HDL and non-HDL lipoproteins and apolipoproteins was characterized. There was an inverse correlation between SR-BI expression and apoA-I and HDL cholesterol levels in transgenic mice fed either mouse chow or a diet high in fat and cholesterol. An unexpected finding in the SR-BI transgenic mice was the dramatic impact of the SR-BI transgene on non-HDL cholesterol and apoB whose levels were also inversely correlated with SR-BI expression. Consistent with the decrease in plasma HDL and non-HDL cholesterol was an accelerated clearance of HDL, non-HDL, and their major associated apolipoproteins in the transgenics compared with control animals. These in vivo studies of the effect of SR-BI overexpression on plasma lipoproteins support the previously proposed hypothesis that SR-BI accelerates the metabolism of HDL and also highlight the capacity of this receptor to participate in the metabolism of non-HDL lipoproteins.