Protection against atherogenesis in mice mediated by human apolipoprotein A-IV
Protection against atherogenesis in mice mediated by human apolipoprotein A-IV
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DOI：
10.1126/science.273.5277.966
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发表时间：
1996-08-16
期刊：
影响因子：
56.9
通讯作者：
Denefle, P
中科院分区：
文献类型：
--
作者：
Duverger, N;Tremp, G;Denefle, P
载脂蛋白是血浆脂质转运颗粒的蛋白质组分。人载脂蛋白A-IV（apoA-IV）在C57 BL/6小鼠和apoE缺陷小鼠的肝脏中表达，这两种小鼠都容易发生动脉粥样硬化，以研究apoA-IV是否可以预防这种疾病。与正常饮食的转基因小鼠相比，在接受致动脉粥样硬化饮食的转基因C57 BL/6小鼠中，高密度脂蛋白（HDL）胆固醇的血清浓度增加了35%，而内源性apoA-I的浓度下降了29%。在正常饮食的apoE缺陷小鼠中表达人apoA-IV导致比非转基因apoE缺陷小鼠更严重的致动脉粥样硬化脂蛋白谱，而不影响HDL胆固醇的浓度。然而，两种背景的转基因小鼠显示动脉粥样硬化病变的大小大幅减少。因此，apoA-IV似乎通过不涉及HDL胆固醇浓度增加的机制来保护免受动脉粥样硬化。
Apolipoproteins ave protein constituents of plasma lipid transport particles. Human apolipoprotein A-IV (apoA-IV) was expressed in the liver of C57BL/6 mice and mice deficient in apoE, both of which are prone to atherosclerosis, to investigate whether apoA-IV protects against this disease. In transgenic C57BL/6 mice on an atherogenic diet, the serum concentration of high density lipoprotein (HDL) cholesterol increased by 35 percent, whereas the concentration of endogenous apoA-I decreased by 29 percent, relative to those in transgenic mice on a normal diet. Expression of human apoA-IV in apoE-deficient mice on a normal diet resulted in an even more severe atherogenic lipoprotein profile, without affecting the concentration of HDL cholesterol, than that in nontransgenic apoE-deficient mice. However, transgenic mice of both backgrounds showed a substantial reduction in the size of atherosclerotic lesions. Thus, apoA-IV appears to protect against atherosclerosis by a mechanism that does not involve an increase in HDL cholesterol concentration.