BACKGROUND Endothelial lipase (EL) plays an important role in lipoprotein metabolism and atherosclerosis. To study the functional roles of EL, we recently generated transgenic (Tg) rabbits and reported that increased hepatic expression of EL in male Tg rabbits significantly reduced diet-induced hypercholesterolemia compared with non-Tg controls. This gender difference suggests that sex hormones may mediate EL functions thereby influencing lipoprotein metabolism. To examine this hypothesis, we compared the effects of orchiectomy and ovariectomy on plasma lipids and diet-induced atherosclerosis in both Tg and non-Tg rabbits. METHODS Male rabbits were under orchiectomy whereas female rabbits were under ovariectomy. We compared plasma lipids, lipoproteins, and apolipoproteins of rabbits before and after surgery in each group fed either a chow diet or cholesterol-rich diet. RESULTS On a chow diet, both male and female Tg rabbits showed lower plasma lipids than non-Tg counterparts and this lipid-lowering effect of EL was not affected by either orchiectomy in male or ovariectomy in female Tg rabbits. On a cholesterol diet; however, male Tg rabbits but not female Tg rabbits showed significant resistance to diet-induced hypercholesterolemia and atherosclerosis. The EL-mediated atheroprotective effect was eliminated after orchiectomy in male Tg rabbits. Female Tg rabbits showed similar levels of total cholesterol and lesion size of atherosclerosis compared with non-Tg rabbits and ovariectomy did not affect diet-induced hypercholesterolemia or atherosclerosis. CONCLUSION These results suggest that increased EL protects against diet-induced hypercholesterolemia and atherosclerosis. The beneficial effect of EL was dependent upon the presence of androgenic hormones.

中文翻译：

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性激素会影响内皮脂肪酶介导的脂质代谢和动脉粥样硬化。

背景技术内皮脂肪酶（EL）在脂蛋白代谢和动脉粥样硬化中起重要作用。为了研究EL的功能作用，我们最近产生了转基因（Tg）兔，并报告说，与非Tg对照相比，雄性Tg兔中EL肝脏表达的增加显着降低了饮食引起的高胆固醇血症。这种性别差异表明性激素可能介导EL功能，从而影响脂蛋白代谢。为了检验这一假设，我们比较了睾丸切除术和卵巢切除术对Tg和非Tg兔血浆脂质和饮食诱导的动脉粥样硬化的影响。方法雄性兔子接受睾丸切除术，雌性兔子接受卵巢切除术。我们比较了血浆脂质，脂蛋白，每组中，兔子在手术前后的载脂蛋白和载脂蛋白均以低脂饮食或高胆固醇饮食为食。结果在日粮中，雄性和雌性Tg兔子的血浆脂质均低于非Tg雌性，而EL的这种降脂作用不受雄性睾丸切除术或雌性Tg兔子卵巢切除术的影响。使用胆固醇饮食；然而，雄性Tg兔而非雌性Tg兔对饮食诱导的高胆固醇血症和动脉粥样硬化表现出明显的抵抗力。雄性Tg兔睾丸切除术后消除了EL介导的抗动脉粥样硬化作用。与非Tg兔相比，雌性Tg兔的总胆固醇水平和病变大小均相似，卵巢切除术不会影响饮食诱发的高胆固醇血症或动脉粥样硬化。结论这些结果表明增加的EL可防止饮食引起的高胆固醇血症和动脉粥样硬化。EL的有益作用取决于雄激素的存在。