Lagor William R, Brown Robert J, Toh Sue-Anne, Millar John S, Fuki Ilia V, de la Llera-Moya Margarita, Yuen Tiffany, Rothblat George, Billheimer Jeffrey T, Rader Daniel J
Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Arterioscler Thromb Vasc Biol. 2009 Jan;29(1):40-6. doi: 10.1161/ATVBAHA.108.177105. Epub 2008 Nov 13.
Apolipoprotein F (ApoF) 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 ApoF 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 ApoF had similar effects. Human ApoF was nearly exclusively HDL-associated in mice. In agreement with this finding, greater than 90% of the ApoF in human plasma was found on HDL(3), with only a small amount on LDL. Overexpression of mouse ApoF accelerated the plasma clearance of [(3)H]-cholesteryl ether labeled HDL. Plasma from mice overexpressing ApoF showed improved macrophage cholesterol efflux on a per HDL-C basis.
ApoF overexpression reduces HDL cholesterol levels in mice by increasing clearance of HDL-CE. ApoF may be an important determinant of HDL metabolism and reverse cholesterol transport.
载脂蛋白F（ApoF）是包括高密度脂蛋白（HDL）在内的几种脂蛋白类别的蛋白质成分。基于其在体外抑制脂蛋白间脂质转移的能力，它也被称为脂质转移抑制蛋白（LTIP）。我们试图研究ApoF在HDL代谢中的作用。
使用基于8型血清型的腺相关病毒（AAV）在小鼠中过表达小鼠或人ApoF。小鼠ApoF的过表达使总胆固醇水平显著降低28%（P<0.001），HDL降低27%（P<0.001），磷脂水平降低19%（P<0.001）。人ApoF的过表达有类似作用。人ApoF在小鼠中几乎完全与HDL相关。与此发现一致，人血浆中超过90%的ApoF存在于HDL(3)上，仅少量存在于低密度脂蛋白（LDL）上。小鼠ApoF的过表达加速了[(3)H] - 胆固醇醚标记的HDL的血浆清除。过表达ApoF的小鼠血浆在每HDL - C基础上显示出改善的巨噬细胞胆固醇流出。
ApoF过表达通过增加HDL - CE的清除降低小鼠HDL胆固醇水平。ApoF可能是HDL代谢和胆固醇逆向转运的重要决定因素。
