The role of apolipoprotein E in high density lipoprotein metabolism

在澳大利亚，冠心病是造成死亡和残疾的主要原因。血液中胆固醇水平高会增加患冠心病的风险。冠状动脉风险的增加是由低密度脂蛋白（LDL）中携带的胆固醇引起的。然而，并非所有的胆固醇都是有害的。血液中的一部分胆固醇携带高密度脂蛋白（HDL），它是预防心脏病的有力保护剂。血液中高密度脂蛋白水平高的人患心脏病的风险显著降低。高密度脂蛋白由几种不同类型的颗粒组成，这些颗粒含有脂质（或脂肪）和蛋白质。并不是所有的高密度脂蛋白都能预防冠心病。我们确定哪种高密度脂蛋白对心脏最具保护作用的能力是有限的，因为很难将不同类型的颗粒分开。我们知道的一件事是，高密度脂蛋白的心脏保护特性和代谢受到它们所含蛋白质的影响。关于两种主要HDL蛋白对HDL代谢和心脏保护特性的影响，我们已经知道了相当多的信息。然而，高密度脂蛋白含有其他几种在这方面也很重要的蛋白质。这个项目关注的是另一种叫做载脂蛋白E的蛋白质。载脂蛋白E预防心脏病的证据是无可争辩的。尽管如此，人们对其在高密度脂蛋白代谢中的作用几乎一无所知。这是因为很难从血浆中分离出大量含载脂蛋白e的高密度脂蛋白。为了克服这些问题，我开发了一种制备含载脂蛋白e的高密度脂蛋白的新方法，这些制剂可与人血浆中含载脂蛋白e的高密度脂蛋白相媲美。本项目将使用它们来研究载脂蛋白E对HDL代谢的影响。

Coronary heart disease is a major cause of death and disability in Australia. A high level of blood cholesterol increases the risk of developing coronary heart disease. This increase in coronary risk is caused by the cholesterol that is carried in low density lipoproteins (LDL). However, not all cholesterol is bad. A proportion of the cholesterol in blood is carried high density lipoproteins (HDL), which are powerful protectors against heart disease. People with high blood levels of HDL have a significantly reduced risk of developing heart disease. HDL consist of several different types of particles that contain lipids (or fats) and proteins. Not all HDL protect equally against coronary heart disease. Our ability to determine which HDL are the most cardioprotective is limited because it is difficult to separate the different types of particles from each other. One thing we do know is that the cardioprotective properties and metabolism of HDL are influenced by the proteins they contain. A considerable amount is known about the effects of the two main HDL proteins on the metabolism and cardioprotective properties of HDL. However, HDL contain several other proteins which are also important in this regard. This project is concerned with one of those other proteins called apolipoprotein E. The evidence that apolipoprotein E protects against heart disease is indisputable. Despite this, almost nothing is known about its role in HDL metabolism. This is because it is difficult to isolate large amounts of apolipoprotein E-containing HDL from plasma. In order to overcome these problems I have developed a novel method for preparing HDL which contain apolipoprotein E. These preparations are comparable to the apoE-containing HDL in human plasma. They will be used in this project to study the influence of apolipoprotein E on HDL metabolism.