McPherson Peter A C, Young Ian S, McKibben Bronac, McEneny Jane
Centre for Clinical and Population Sciences, Nutrition and Metabolism Group, Queen's University, Belfast, United Kingdom.
J Lipid Res. 2007 Jan;48(1):86-95. doi: 10.1194/jlr.M600094-JLR200. Epub 2006 Oct 25.
The plasma HDLs represent a major class of cholesterol-transporting lipoprotein that can be divided into two distinct subfractions, HDL(2) and HDL(3), by ultracentrifugation. Existing methods for the subfractionation of HDL requires lengthy ultracentrifugations, making them unappealing for large-scale studies. We describe a method that subfractionates HDL from plasma in only 6 h, representing a substantial decrease in total isolation time. The subfractions so isolated were assessed for a variety of lipid and protein components, in addition to their susceptibility to oxidation, both alone and in combination with VLDL and LDL. We report for the first time a prooxidant role for HDL during VLDL oxidation, in which HDL donates preformed hydroperoxides to VLDL in a cholesteryl ester transfer protein (CETP)-dependent process. Examination of the participation of HDL in LDL oxidation has reinforced its classic role as a potent antioxidant. Furthermore, we have also implicated the second major HDL-associated enzyme, LCAT, in these processes, whereby it acts as a potent prooxidant during VLDL oxidation but as an antioxidant during LDL oxidation. Thus, we have identified a potentially duplicitous role for HDL in the pathogenesis of atherosclerosis, attributable to both CETP and LCAT.
血浆高密度脂蛋白（HDL）是一类主要的胆固醇转运脂蛋白，通过超速离心可分为两个不同的亚组分，即HDL(2)和HDL(3)。现有的HDL亚组分分离方法需要长时间的超速离心，这使得它们对于大规模研究缺乏吸引力。我们描述了一种仅需6小时就能从血浆中分离HDL亚组分的方法，这代表着总分离时间大幅减少。除了单独以及与极低密度脂蛋白（VLDL）和低密度脂蛋白（LDL）联合时对氧化的敏感性外，还对如此分离得到的亚组分的各种脂质和蛋白质成分进行了评估。我们首次报道了HDL在VLDL氧化过程中的促氧化作用，即在胆固醇酯转移蛋白（CETP）依赖的过程中，HDL将预先形成的氢过氧化物捐赠给VLDL。对HDL参与LDL氧化的研究强化了其作为强效抗氧化剂的经典作用。此外，我们还发现HDL相关的第二种主要酶——卵磷脂胆固醇酰基转移酶（LCAT）也参与了这些过程，即在VLDL氧化过程中它作为强效促氧化剂起作用，但在LDL氧化过程中作为抗氧化剂起作用。因此，我们确定了HDL在动脉粥样硬化发病机制中可能具有的双重作用，这归因于CETP和LCAT。
