Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet-Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits.
Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet-Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits.
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DOI：
10.1161/atvbaha.117.309139
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发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Fan J
中科院分区：
文献类型：
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作者：
Wang C;Nishijima K;Kitajima S;Niimi M;Yan H;Chen Y;Ning B;Matsuhisa F;Liu E;Zhang J;Chen YE;Fan J
内皮脂酶（EL）是血浆HDL-C的关键决定因素。然而，EL在动脉粥样硬化发展中的功能作用尚未阐明。我们研究了肝脏EL表达是否影响血浆脂蛋白代谢和胆固醇饮食诱导的动脉粥样硬化。我们产生了转基因（Tg）兔在肝脏中表达的人EL基因，然后检查EL表达对血脂和脂蛋白的影响，并比较了Tg兔的易感性胆固醇饮食诱导的动脉粥样硬化与非Tg同窝出生。在普通饲料中，与非Tg对照组相比，Tg兔中人EL的肝脏表达导致血浆总胆固醇、磷脂和HDL-胆固醇水平显著降低。在富含胆固醇的饮食16周，Tg兔表现出显着较低的高胆固醇血症和动脉粥样硬化比非Tg同窝仔。在Tg兔中，主动脉粥样硬化的总病变面积减少了52%，病变的特点是与非Tg同窝仔相比，巨噬细胞和平滑肌细胞较少。EL的肝脏表达增加可减弱胆固醇饮食诱导的高胆固醇血症并预防动脉粥样硬化。
Endothelial lipase (EL) is a key determinant in plasma HDL-C. However, functional roles of EL on the development of atherosclerosis have not been clarified. We investigated whether hepatic expression of EL affects plasma lipoprotein metabolism and cholesterol diet-induced atherosclerosis. We generated transgenic (Tg) rabbits expressing the human EL gene in the liver and then examined the effects of EL expression on plasma lipids and lipoproteins and compared the susceptibility of Tg rabbits to cholesterol diet-induced atherosclerosis with non-Tg littermates. On a chow diet, hepatic expression of human EL in Tg rabbits led to remarkable reductions in plasma levels of total cholesterol, phospholipids, and HDL-cholesterol compared with non-Tg controls. On a cholesterol-rich diet for 16 weeks, Tg rabbits exhibited significantly lower hypercholesterolemia and less atherosclerosis than non-Tg littermates. In Tg rabbits, gross lesion area of aortic atherosclerosis was reduced by 52%, and the lesions were characterized by fewer macrophages and smooth muscle cells compared with non-Tg littermates. Increased hepatic expression of EL attenuates cholesterol diet-induced hypercholesterolemia and protects against atherosclerosis.