Das Undurti N
UND Life Sciences, 1083 Main Street, Walpole, MA 02081, USA.
Prostaglandins Leukot Essent Fatty Acids. 2005 Mar;72(3):173-9. doi: 10.1016/j.plefa.2004.10.016.
Endothelial lipase (EL), a new member of the lipase gene family, was recently cloned and has been shown to have a significant role in modulating the concentrations of plasma high-density lipoprotein levels (HDL). EL is closely related to lipoprotein and hepatic lipases both in structure and function. It is primarily synthesized by endothelial cells, functions at the cell surface, and shows phospholipase A1 activity. Overexpression of EL decreases HDL cholesterol levels whereas blocking its action increases concentrations of HDL cholesterol. Pro-inflammatory cytokines suppress plasma HDL cholesterol concentrations by enhancing the activity of EL. On the other hand, physical exercise and fish oil (a rich source of eicosapentaenoic acid and docosahexaenoic acid) suppress the activity of EL and this, in turn, enhances the plasma concentrations of HDL cholesterol. Thus, EL plays a critical role in the regulation of plasma HDL cholesterol concentrations and thus modulates the development and progression of atherosclerosis. The expression and actions of EL in specific endothelial cells determines the initiation and progression of atherosclerosis locally explaining the patchy nature of atheroma seen, especially, in coronary arteries. Both HDL cholesterol and EPA and DHA enhance endothelial nitric oxide (eNO) and prostacyclin (PGI2) synthesis, which are known to prevent atherosclerosis. On the other hand, pro-inflammatory cytokines augment free radical generation, which are known to inactivate eNO and PGI2. Thus, interactions between EL, pro- and anti-inflammatory cytokines, polyunsaturated fatty acids, and the ability of endothelial cells to generate NO and PGI2 and neutralize the actions of free radicals may play a critical role in atherosclerosis.
内皮脂肪酶（EL）是脂肪酶基因家族的一个新成员，最近已被克隆，并且已证明其在调节血浆高密度脂蛋白水平（HDL）浓度方面具有重要作用。EL在结构和功能上都与脂蛋白脂肪酶和肝脂肪酶密切相关。它主要由内皮细胞合成，在细胞表面发挥作用，并表现出磷脂酶A1活性。EL的过度表达会降低HDL胆固醇水平，而阻断其作用则会增加HDL胆固醇的浓度。促炎细胞因子通过增强EL的活性来抑制血浆HDL胆固醇浓度。另一方面，体育锻炼和鱼油（二十碳五烯酸和二十二碳六烯酸的丰富来源）会抑制EL的活性，进而提高血浆HDL胆固醇的浓度。因此，EL在调节血浆HDL胆固醇浓度方面起着关键作用，从而调节动脉粥样硬化的发生和发展。EL在特定内皮细胞中的表达和作用决定了动脉粥样硬化的起始和进展，局部解释了尤其是在冠状动脉中所见的动脉粥样斑块的斑块状性质。HDL胆固醇以及EPA和DHA均可增强内皮一氧化氮（eNO）和前列环素（PGI2）的合成，已知它们可预防动脉粥样硬化。另一方面，促炎细胞因子会增加自由基的产生，已知自由基会使eNO和PGI2失活。因此，EL、促炎和抗炎细胞因子、多不饱和脂肪酸之间的相互作用，以及内皮细胞产生NO和PGI2并中和自由基作用的能力，可能在动脉粥样硬化中起关键作用。
