Elucidation of endothelial lipase as a new therapeutic strategy foratherosclerosis: a study using transgenic rabbits

阐明内皮脂肪酶作为动脉粥样硬化新治疗策略：一项使用转基因兔子的研究

• 批准号: 22390068
• 负责人: FAN Jianglin
• 金额: $ 10.4万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390068/
• 关键词: 高脂血症; 動脈硬化; 遺伝子改変ウサギ; HDL; アンチセンス; 内皮リパーゼ; ウサギ; EL; 遺伝子改変; リパーゼ; ウサギモデル

Existing evidence suggests that endothelial lipase (EL) plays an important role inhigh-density-lipoprotein (HDL) metabolism. First, we cloned the rEL cDNA and gene ofrabbits. Using Northern blotting, real-time RT-PCR, Western blotting, and in situhybridization, we revealed that rEL mRNA was highly expressed in the cholesterolsynthesis-related organs including the liver, testis, and adrenal along with itsexpression in the lung, kidney, bone marrow, and small intestine. The plasma HDL levelsin WHHL rabbits were inversely associated with high levels of plasma rEL proteins andhepatic expression of rEL mRNA. Injection of rEL-specific antisense oligonucleotides intorabbits resulted in an elevation of plasma large-sized HDLs. Furthermore, we demonstratedthat the rEL mRNA was expressed by both endothelial cells and macrophages in the lesionsof aortic atherosclerosis of WHHL rabbits. rEL is expressed in multiple tissues and mayhave many physiological and pathophysiological functions such as in the regulation ofcholesterol metabolism and atherosclerosis. Our results suggest that EL is an importantregulator of plasma HDL levels in rabbits. In addition, we generated two transgenicrabbits expressing different levels of human EL in the liver

现有证据表明，内皮脂酶（EL）在高密度脂蛋白（HDL）代谢中起重要作用。首先，我们克隆了rEL的cDNA和兔的基因。利用北方印迹、实时荧光定量RT-PCR、Western印迹和原位杂交技术，我们发现rEL mRNA在胆固醇合成相关器官中高表达，包括肝脏、睾丸和肾上腺，沿着其在肺、肾、骨髓和小肠中的表达。WHHL兔血浆HDL水平与血浆rEL蛋白水平及肝脏rEL mRNA表达水平呈负相关。兔体内注射rEL特异性反义寡核苷酸导致血浆大分子HDL升高。此外，我们还证实在WHHL兔主动脉粥样硬化病变中，内皮细胞和巨噬细胞均表达rEL mRNA。rEL在多种组织中表达，可能具有调节胆固醇代谢、动脉粥样硬化等多种生理和病理生理功能。结果提示，EL是家兔血浆HDL水平的重要调节剂。此外，我们还制备了两只在肝脏中表达不同水平人EL的转基因兔，

项目成果

Immunohistochemicaldemonstration of apolipoprotein b-48in the lesions of humanatherosclerosis

载脂蛋白b-48在人动脉粥样硬化病变中的免疫组织化学研究

• 发表时间: 2012
• 作者: 戸塚直也;田原聡子;永井恵;小田(中橋)ちぐさ;人見香織;栗田尚樹;本多伸一郎;渋谷和子;渋谷彰;澤下仁子;Liu ZC
• 通讯作者: Liu ZC

Production of apolipoprotein C-III knockout rabbits using zinc finger nucleases.

• DOI: 10.3791/50957
• 发表时间: 2013-11-18
• 期刊: Journal of visualized experiments : JoVE
• 作者: Yang D;Zhang J;Xu J;Zhu T;Fan Y;Fan J;Chen YE
• 通讯作者: Chen YE

内皮リパーゼ特異的アンチセンスによる発現阻害効果とHDL代謝への影響

内皮脂肪酶特异性反义对表达抑制和 HDL 代谢的影响

• 发表时间: 2010
• 作者: Yu Y;Koike T;Zhang X Zhang J;Fan J
• 通讯作者: Fan J

Transgenic rabbit models for the study of atherosclerosis.

用于研究动脉粥样硬化的转基因兔模型。

• DOI: 10.2741/a192
• 发表时间: 1997
• 期刊: Frontiers in bioscience : a journal and virtual library
• 作者: Taylor,JM;Fan,J
• 通讯作者: Fan,J

動脈硬化の分子病態の解明及びトランスレーショナルリサーチへの挑戦

阐明动脉硬化的分子病理学并迎接转化研究的挑战

• 发表时间: 2010
• 作者: Reifenberg K;et al.;Koike T;Liu E;Fan J;Niimi M;Liu G;Koike T;Zhang J;Koike T;範江林;範江林;範江林
• 通讯作者: 範江林