内皮脂肪酶肝脏表达增加可抑制转基因兔胆固醇饮食诱导的高胆固醇血症和动脉粥样硬化。
Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet-Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits.
作者信息
Wang Chuan, Nishijima Kazutoshi, Kitajima Shuji, Niimi Manabu, Yan Haizhao, Chen Yajie, Ning Bo, Matsuhisa Fumikazu, Liu Enqi, Zhang Jifeng, Chen Y Eugene, Fan Jianglin
机构信息
From the Department of Molecular Pathology, Faculty of Medicine, Graduate Faculty of Interdisciplinary Research, Graduate School, University of Yamanashi, Japan (C.W., M.N., B.N., H.Y., Y.C., J.F.); Department of Pathology, Xi'an Medical University, China (B.N., J.F.); Animal Research Laboratory, Bioscience Education-Research Support Center, Akita University, Japan (K.N.); Analytical Research Center for Experimental Sciences, Saga University, Japan (S.K., F.M.); Research Institute of Atherosclerotic Disease and Laboratory Animal Center, Xi'an Jiaotong University School of Medicine, China (E.L.); and Center for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical Center, Ann Arbor (J.Z., Y.E.C.).
出版信息
Arterioscler Thromb Vasc Biol. 2017 Jul;37(7):1282-1289. doi: 10.1161/ATVBAHA.117.309139. Epub 2017 May 25.
OBJECTIVE
Endothelial lipase (EL) is a key determinant in plasma high-density lipoprotein-cholesterol. 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.
APPROACH AND RESULTS
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 with 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 high-density lipoprotein-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.
CONCLUSIONS
Increased hepatic expression of EL attenuates cholesterol diet-induced hypercholesterolemia and protects against atherosclerosis.
目的
内皮脂肪酶（EL）是血浆高密度脂蛋白胆固醇的关键决定因素。然而，EL在动脉粥样硬化发展中的功能作用尚未阐明。我们研究了肝脏中EL的表达是否会影响血浆脂蛋白代谢以及胆固醇饮食诱导的动脉粥样硬化。
方法与结果
我们培育了在肝脏中表达人EL基因的转基因（Tg）兔，然后检测EL表达对血浆脂质和脂蛋白的影响，并将Tg兔与胆固醇饮食诱导的动脉粥样硬化的易感性与非Tg同窝仔兔进行比较。在普通饮食条件下，与非Tg对照相比，Tg兔肝脏中人类EL的表达导致血浆总胆固醇、磷脂和高密度脂蛋白胆固醇水平显著降低。在富含胆固醇的饮食16周后，Tg兔表现出比非Tg同窝仔兔显著更低的高胆固醇血症和更少的动脉粥样硬化。在Tg兔中，主动脉粥样硬化的大体病变面积减少了52%，与非Tg同窝仔兔相比，病变特征为巨噬细胞和平滑肌细胞较少。
结论
肝脏中EL表达增加可减轻胆固醇饮食诱导的高胆固醇血症并预防动脉粥样硬化。
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