Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo-City, Japan.
J Atheroscler Thromb. 2012;19(3):213-26. doi: 10.5551/jat.11148. Epub 2012 Jan 12.
Existing evidence suggests that endothelial lipase (EL) plays an important role in high-densitylipoprotein (HDL) metabolism. Because rabbits are a useful animal model for the study of human lipid metabolism and atherosclerosis, we characterized rabbit EL (rEL) expression and investigated its relationship with plasma HDL levels in normal and hyperlipidemic rabbits.
We cloned the rEL cDNA and analyzed the EL tissue expression using Northern blotting, real-time RT-PCR, Western blotting, and in situ hybridization. We evaluated the effects of rEL antisense on plasma HDL levels.
We found that rEL mRNA was highly expressed in 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 the elevation of plasma large HDLs. Furthermore, we demonstrated that rEL mRNA was expressed by both endothelial cells and macrophages in the lesions of aortic atherosclerosis of WHHL rabbits.
rEL 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.
现有证据表明内皮脂肪酶（EL）在高密度脂蛋白（HDL）代谢中发挥重要作用。由于兔子是研究人类脂质代谢和动脉粥样硬化的有用动物模型，我们对兔 EL（rEL）的表达进行了表征，并研究了其与正常和高脂血症兔子血浆 HDL 水平的关系。
我们克隆了 rEL cDNA，并通过 Northern 印迹、实时 RT-PCR、Western 印迹和原位杂交分析了 EL 组织表达。我们评估了 rEL 反义对血浆 HDL 水平的影响。
我们发现 rEL mRNA 在胆固醇合成相关器官中高度表达，包括肝脏、睾丸和肾上腺，以及肺、肾脏、骨髓和小肠。有趣的是，Watanabe 遗传性高脂血症（WHHL）兔是人类家族性高胆固醇血症的模型，其血浆 HDL 水平低于正常兔。WHHL 兔的血浆 HDL 水平与血浆 rEL 蛋白水平升高和肝 rEL mRNA 表达呈负相关。向兔子注射 rEL 特异性反义寡核苷酸可导致血浆大 HDL 升高。此外，我们证明 rEL mRNA 由 WHHL 兔主动脉粥样硬化病变中的内皮细胞和巨噬细胞表达。
rEL 在多种组织中表达，可能具有许多生理和病理生理功能，如调节胆固醇代谢和动脉粥样硬化。我们的结果表明，EL 是兔子血浆 HDL 水平的重要调节因子。
