Overexpression of apolipoprotein F reduces HDL cholesterol levels in vivo.
Overexpression of apolipoprotein F reduces HDL cholesterol levels in vivo.
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DOI：
10.1161/atvbaha.108.177105
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发表时间：
2009-01
期刊：
影响因子：
--
通讯作者：
Rader DJ
中科院分区：
文献类型：
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作者：
Lagor WR;Brown RJ;Toh SA;Millar JS;Fuki IV;de la Llera-Moya M;Yuen T;Rothblat G;Billheimer JT;Rader DJ
载脂蛋白F （Apo F）是包括HDL在内的几种脂蛋白类的蛋白质成分。它也被称为脂质转移抑制蛋白（LTIP），因为它能够在体外抑制脂蛋白之间的脂质转移。我们试图研究载脂蛋白F在HDL代谢中的作用。基于血清型8的腺相关病毒（AAV）在小鼠中过表达鼠或人ApoF。过表达小鼠ApoF可显著降低总胆固醇水平28% (p < 0.001)，降低高密度脂蛋白27% (p < 0.001)，降低磷脂水平19% （p < 0.001）。人类Apo F的过表达也有类似的效果。人类载脂蛋白F在小鼠中几乎完全与高密度脂蛋白相关。与这一发现一致的是，人类血浆中超过90%的载脂蛋白F存在于HDL3上，只有少量存在于LDL上。小鼠Apo F的过度表达加速了血浆中[3H]-胆固醇醚标记HDL的清除。过表达载脂蛋白F的小鼠血浆显示，巨噬细胞胆固醇外流在每个HDL-C的基础上得到改善。载脂蛋白F过表达通过增加HDL- ce清除率降低小鼠高密度脂蛋白胆固醇水平。载脂蛋白F可能是HDL代谢和逆向胆固醇转运的重要决定因素。
Apolipoprotein F (Apo F) is a protein component of several lipoprotein classes including HDL. It is also known as lipid transfer inhibitor protein (LTIP) based on its ability to inhibit lipid transfer between lipoproteins ex vivo. We sought to investigate the role of Apo F in HDL metabolism. Adeno-associated viruses (AAV) based on serotype 8, were used to overexpress either murine or human ApoF in mice. Overexpression of murine ApoF significantly reduced total cholesterol levels by 28% (p < 0.001), HDL by 27% (p < 0.001), and phospholipid levels by 19% (p < 0.001). Overexpression of human Apo F had similar effects. Human Apo F was nearly exclusively HDL-associated in mice. In agreement with this finding, greater than 90% of the Apo F in human plasma was found on HDL3, with only a small amount on LDL. Overexpression of mouse Apo F accelerated the plasma clearance of [3H]-cholesteryl ether labeled HDL. Plasma from mice overexpressing Apo F showed improved macrophage cholesterol efflux on a per HDL-C basis. Apo F overexpression reduces HDL cholesterol levels in mice by increasing clearance of HDL-CE. Apo F may be an important determinant of HDL metabolism and reverse cholesterol transport.