Effect of altered expression of endothelial lipase on plasma lipids and atherosclerosis in rabbits

内皮脂肪酶表达改变对家兔血脂和动脉粥样硬化的影响

• 批准号: 23790854
• 负责人: SUN Li
• 金额: $ 2.66万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23790854/
• 关键词: 高比重リポ蛋白; 炎症; 脂質代謝; 血管内皮; リパーゼ; 動脈硬化; 家兎; HDL; 血管内皮リパーゼ; lipase

Endothelial lipase (EL) regulates circulating high-density lipoprotein-cholesterol (HDL-C) levels. There is a discrepancy of EL effect in lipid profiles between mise and humans. Therefore, we investigated the effect of altered EL expression on lipid profile and HDL anti-atherogenic properties in rabbits. Adenovirus encoding human EL (AdhEL) was injected into Japanese white rabbits, which induced hEL overexpression. Consequently, serum HDL-C levels were significantly decreased, while LDL-C levels were not affected. Lipoprotein fractions isolated from humans, rabbits and mice were treated with the EL-rich medium, and measured free fatty acids liberated from the lipoprotein substrates. The hEL hydrolyzed HDL from all three species, while it hydrolyzed mouse LDL much greater than rabbit- and human-LDL. Serum paraoxonase activity, a major component of HDL anti-oxidant properties, significantly reducedin EL-overexpressing rabbits, whereas serum cholesterol efflux capacity did not change despite of the reduced HDL levels. In conclusion, Human EL reduced HDL-C and HDL anti-oxidative property in rabbits. Considering that lipid profile of rabbits resembles that of humans, alteration of EL expression or activity may improve HDLlevels and anti-oxidant properties without affecting LDL-C levels in humans.

内皮脂肪酶（EL）调节循环高密度脂蛋白 - 胆固醇（HDL-C）水平。在米斯和人类之间的脂质谱中，EL效应存在差异。因此，我们研究了EL表达对兔子中脂质谱和HDL抗动脉粥样硬化特性的影响。将编码人类EL（ADHEL）的腺病毒注入日本白兔子中，这些兔子诱导HEL过表达。因此，血清HDL-C水平显着降低，而LDL-C水平不影响。用富含EL的培养基处理从人类，兔子和小鼠分离的脂蛋白级分，并测量从脂蛋白底物中释放的游离脂肪酸。 HEL从所有三个物种中水解HDL，而水解小鼠LDL远大于兔和人类LDL。血清二氧蛋白酶活性是HDL抗氧化特性的主要组成部分，显着降低了EL过表达的兔子，而血清胆固醇外排的能力并未改变，尽管HDL水平降低。总之，人类EL降低了兔子中的HDL-C和HDL抗氧化特性。考虑到兔子的脂质谱类似于人类的脂质，因此EL表达或活性的改变可能会改善HDLlevels和抗氧化特性，而不会影响人类的LDL-C水平。

项目成果

Generation of a high-sensitive and reliable ELISA system that can quantitatively measure human serum mass of endothelial lipase

建立高灵敏度、可靠的 ELISA 系统，可定量测量人血清内皮脂肪酶质量

• 发表时间: 2012
• 作者: 宮下かずや;石田達郎;安田知行;孫麗;木下憲明;中嶋克行;平田健一
• 通讯作者: 平田健一

Plasma mass and activity of endothelial lipase are associated with coronary risk factors in humans

血浆质量和内皮脂肪酶活性与人类冠状动脉危险因素相关

• 发表时间: 2012
• 作者: Ishida T;Mori K;Sun L;Yasuda T;Hirata K
• 通讯作者: Hirata K

Effect of overexpression of endothelial lipase on HDL metabolism and HDL anti-atherogenic properties in rabbits

内皮脂肪酶过表达对兔 HDL 代谢和 HDL 抗动脉粥样硬化特性的影响

• 发表时间: 2013
• 作者: Yasuda T;Ishida T;Mori K;Hirata K
• 通讯作者: Hirata K

Expression of Endothelial Lipase Correlates with the Size of Neointima in a Murine Model of Vascular Remodeling

• DOI: 10.5551/jat.13110
• 发表时间: 2012-01-01
• 期刊: JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
• 影响因子: 4.4
• 作者: Sun, Li;Ishida, Tatsuro;Hirata, Ken-ichi
• 通讯作者: Hirata, Ken-ichi

Role of endothelial lipase in HDL metabolism and atherosclerosis in humans

内皮脂肪酶在人类高密度脂蛋白代谢和动脉粥样硬化中的作用

• 发表时间: 2011
• 作者: Ishida T;Toh R;Sun L;Yasuda T;Hirata K
• 通讯作者: Hirata K