Endothelial lipase mediates HDL levels in normal and hyperlipidemic rabbits.
Endothelial lipase mediates HDL levels in normal and hyperlipidemic rabbits.
复制标题
DOI：
10.5551/jat.11148
复制
发表时间：
2012
影响因子：
4.4
通讯作者：
Fan J
中科院分区：
文献类型：
--
作者：
Zhang J;Yu Y;Nakamura K;Koike T;Waqar AB;Zhang X;Liu E;Nishijima K;Kitajima S;Shiomi M;Qi Z;Yu J;Graham MJ;Crooke RM;Ishida T;Hirata K;Hurt-Camejo E;Chen YE;Fan J
现有证据表明，内皮脂肪酶（EL）在高密度脂蛋白（HDL）代谢中起重要作用。由于家兔是研究人类脂质代谢和动脉粥样硬化的有效动物模型，我们对家兔组织EL表达进行了表征，并研究了其与正常和高脂血症家兔血浆HDL水平的关系。首先，我们克隆了兔EL (rEL) cDNA及其基因。通过Northern blotting、real-time RT-PCR、Western blotting和原位杂交，我们发现relmrna在肝脏、睾丸和肾上腺等与胆固醇合成相关的器官中高表达，同时在肺、肾、骨髓和小肠中也有表达。有趣的是，Watanabe遗传性高脂血症（WHHL）兔（人类家族性高胆固醇血症的一种模型）的血浆hdl水平低于正常兔。WHHL家兔血浆HDL水平与血浆rEL蛋白水平和肝脏rEL mRNA表达呈负相关。家兔注射rel特异性反义寡核苷酸可引起血浆大尺寸hdl升高。此外，我们发现在WHHL家兔主动脉粥样硬化病变中，内皮细胞和巨噬细胞都表达了relmrna。EL在多种组织中表达，可能具有多种生理和病理生理功能，如调节胆固醇代谢和动脉粥样硬化。我们的研究结果表明，EL是家兔血浆HDL水平的重要调节因子。
Existing evidence suggests that endothelial lipase (EL) plays an important role in high-density-lipoprotein (HDL) metabolism. Because rabbits are a useful animal model for the study of human lipid metabolism and atherosclerosis, we characterized rabbit tissue EL expression and investigated its relationship with plasma HDL levels in normal and hyperlipidemic rabbits. First, we cloned the rabbit EL (rEL) cDNA and gene. Using Northern blotting, real-time RT-PCR, Western blotting, and in situ hybridization, we revealed that rEL mRNA was highly expressed in the cholesterol synthesis-related organs including the liver, testis, and adrenal along with its expression in the lung, kidney, bone marrow, and small intestine. Interestingly, Watanabe heritable hyperlipidemic (WHHL) rabbits, a model of human familial hypercholesterolemia, had lower plasma levels of HDLs than normal rabbits. The plasma HDL levels in WHHL rabbits were inversely associated with high levels of plasma rEL proteins and hepatic expression of rEL mRNA. Injection of rEL-specific antisense oligonucleotides into rabbits resulted in an elevation of plasma large-sized HDLs. Furthermore, we demonstrated that the rEL mRNA was expressed by both endothelial cells and macrophages in the lesions of aortic atherosclerosis of WHHL rabbits. EL is expressed in multiple tissues and may have many physiological and pathophysiological functions such as in the regulation of cholesterol metabolism and atherosclerosis. Our results suggest that EL is an important regulator of plasma HDL levels in rabbits.
登录
查看更多内容
影响因子：
37.8
作者：
Koike T;Kitajima S;Yu Y;Nishijima K;Zhang J;Ozaki Y;Morimoto M;Watanabe T;Bhakdi S;Asada Y;Chen YE;Fan J
通讯作者：
Fan J
影响因子：
10.8
作者：
Shimokawa, Y;Hirata, K;Yokoyama, M
通讯作者：
Yokoyama, M
影响因子：
56.9
作者：
YAMAMOTO, T;BISHOP, RW;RUSSELL, DW
通讯作者：
RUSSELL, DW
影响因子：
8.7
作者：
HOKANSON, JE;KRAUSS, RM;BRUNZELL, JD
通讯作者：
BRUNZELL, JD
代谢综合征中的内皮脂肪酶浓度增加，并与冠状动脉粥样硬化有关。
影响因子：
15.8
作者：
Badellino, KO;Wolfe, ML;Reilly, MP;Rader, DJ
通讯作者：
Rader, DJ