Badellino Karen O, Rader Daniel J
School of Nursing, University of Pennsylvania, Philadelphia 19104, USA.
Curr Opin Cardiol. 2004 Jul;19(4):392-5. doi: 10.1097/01.hco.0000130161.89169.02.
Elevating high-density lipoprotein levels is increasingly being identified as an essential strategy for the prevention of atherosclerosis. Plasma levels of high-density lipoprotein cholesterol and its major protein, apoAI, are largely influenced by the rate of turnover. Lipases play an important role in modulating the metabolism of high-density lipoprotein. In particular, endothelial lipase has been shown to be an important determinant of high-density lipoprotein metabolism and levels in murine models. This article reviews new developments in our understanding of the biology of endothelial lipase and its relation to high-density lipoprotein metabolism.
Inhibition of the endothelial lipase gene, either by antibody injection or by targeted gene deletion, results in an approximately 50% increase in high-density lipoprotein cholesterol levels in mice. As many as 31 single-nucleotide polymorphisms have been identified in the endothelial lipase gene. The 584 C/T mutation, which results in a threonine-to-isoleucine amino acid change, has been associated with higher high-density lipoprotein cholesterol levels in three separate studies.
Increasing evidence suggests that endothelial lipase plays a significant role in high-density lipoprotein metabolism. Endothelial lipase could be an important new target for novel therapies to raise high-density lipoprotein levels.
提高高密度脂蛋白水平日益被视为预防动脉粥样硬化的重要策略。血浆中高密度脂蛋白胆固醇及其主要蛋白质载脂蛋白AI的水平在很大程度上受周转率影响。脂酶在调节高密度脂蛋白代谢中起重要作用。特别是，在内皮细胞模型中，内皮脂肪酶已被证明是高密度脂蛋白代谢和水平的重要决定因素。本文综述了我们对内皮脂肪酶生物学及其与高密度脂蛋白代谢关系理解的新进展。
通过抗体注射或靶向基因缺失抑制内皮脂肪酶基因，可使小鼠高密度脂蛋白胆固醇水平升高约50%。在内皮脂肪酶基因中已鉴定出多达31个单核苷酸多态性。在三项独立研究中，导致苏氨酸至异亮氨酸氨基酸变化的584 C/T突变与较高的高密度脂蛋白胆固醇水平相关。
越来越多的证据表明，内皮脂肪酶在高密度脂蛋白代谢中起重要作用。内皮脂肪酶可能成为提高高密度脂蛋白水平新疗法的重要新靶点。
