A novel endothelial-derived lipase that modulates HDL metabolism
A novel endothelial-derived lipase that modulates HDL metabolism
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DOI：
10.1038/7766
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发表时间：
1999-04-01
期刊：
影响因子：
30.8
通讯作者：
Rader, DJ
中科院分区：
文献类型：
--
作者：
Jaye, M;Lynch, KJ;Rader, DJ
高密度脂蛋白（HDL）胆固醇水平与动脉粥样硬化性心血管疾病的风险呈负相关（1）。至少50%的HDL胆固醇水平的变化是由遗传决定的（2，3），但负责HDL水平变化的基因尚未完全阐明。脂蛋白脂肪酶（LPL）和肝脂肪酶（HL）是三酰甘油（TC）脂肪酶家族的两个成员，均影响HDL代谢（2，4 -6），HL（LIPC）基因座与人体HDL胆固醇水平的变化相关（7，8）。我们在这里描述的TG脂肪酶家族的一个新成员的克隆和体内功能分析。与其他家族成员相比，这种新的脂肪酶由内皮细胞在体外合成，因此被称为内皮脂肪酶（由LIPG基因编码）。EL在体内器官中表达，包括肝、肺、肾和胎盘，但在骨骼肌中不表达。与LPL和HL相反，EL具有仅19个残基的盖。EL具有显著的磷脂酶活性，但甘油三酯脂肪酶活性较低。EL在小鼠中的过表达降低了HDL胆固醇及其主要蛋白载脂蛋白A-I的血浆浓度。EL的内皮表达、酶谱和体内作用表明它可能在脂蛋白代谢和血管生物学中起作用。
High-density lipoprotein (HDL) cholesterol levels are inversely associated with risk of atherosclerotic cardiovascular disease(1). At least 50% of the variation in HDL cholesterol levels is genetically determined(2,3), but the genes responsible for variation in HDL levels have not been fully elucidated. Lipoprotein lipase (LPL) and hepatic lipase (HL), two members of the triacylglyerol (TC) lipase family, both influence HDL metabolism(2,4-6) and the HL (LIPC) locus has been associated with variation in HDL cholesterol levels in humans(7,8). We describe here the cloning and in vivo functional analysis of a new member of the TG lipase family. In contrast to other family members, this new lipase is synthesized by endothelial cells in vitro and thus has been termed endothelial lipase (encoded by the LIPG gene). EL is expressed in vivo in organs including liver, lung, kidney and placenta, but not in skeletal muscle. In contrast to LPL and HL, EL has a lid of only 19 residues. EL has substantial phospholipase activity, but less triglyceride lipase activity. Overexpression of EL in mice reduced plasma concentrations of HDL cholesterol and its major protein apolipoprotein A-I. The endothelial expression, enzymatic profile and in vivo effects of EL suggest that it may have a role in lipoprotein metabolism and vascular biology.