内皮脂肪酶与高密度脂蛋白胆固醇代谢、胆固醇逆转运、动脉粥样硬化的关系研究进展

Research Progress in the Role of Endothelial Lipase in High-Density Lipoprotein Metabolism,Reverse Cholesterol Transport and Atherosclerosis

胆固醇逆转运(RCT)是高密度脂蛋白(HDL)抗动脉粥样硬化的关键组成部分。内皮脂肪酶(EL)在高密度脂蛋白胆固醇(HDL-C)代谢过程中起着重要的作用,它对血浆HDL-C水平起负调节作用。尽管EL的过表达减少总RCT,但EL剔除并未使RCT受影响。EL虽能增加肝脏选择性的胆固醇摄取,但最终并没有将其转化,也未从胆汁、粪便中排泄。炎性因子,包括肿瘤坏死因子α和白细胞介素1β均能够正调节EL的表达,同时EL也能够影响这些细胞因子的表达,它们都在动脉粥样硬化中起着重要的作用。但EL对动脉粥样硬化的影响并不明确,在人体动脉粥样硬化病变中巨噬细胞也与EL有关。研究认识EL的生物特性,以期将EL作为对动脉粥样硬化心血管病的治疗靶点。

Reverse cholesterol transport（RCT） is a key part of the atheroprotective properties of highdensity lipoproteins （HDL）. Endothelial lipase （EL）plays an important role in high-density lipoprotein metabolism, which negatively regulates plasma HDL cholesterol levels. Although overexpression of EL decreases overall RCT,knockout of EL leaves RCT essentially unaffected. EL increase hepatic selective cholesterol uptake, however, this does not translate into altered biliary cholesterol and feces secretion. Inflammatory cytokines, including tumor necrosis factor-α （TNF-α） and interleukin-1 β （ IL-1 β ）, upregulate endothelial lipase expression,and endothelial lipase also affects the expression of cytokines, which in turn plays an important role in atherogenesis. The impact of EL on atherosclerosis is not clear yet. EL expression has been associated with macrophages within human atherosclerotic lesions. Studying the biological features of EL is expected to establish EL as targets for the treatment of atherosclerotic cardiovascular disease.