The role of apolipoprotein E in high density lipoprotein metabolism

在澳大利亚，冠心病是导致死亡和残疾的主要原因。高水平的血液胆固醇会增加罹患冠心病的风险。这种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，并不是所有的胆固醇都是有害的。血液中胆固醇的一部分携带高密度脂蛋白(HDL)，高密度脂蛋白是预防心脏病的强大保护剂。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含有脂质(或脂肪)和蛋白质的颗粒组成。并不是所有的高密度脂蛋白都能同等地预防冠心病。我们确定哪些高密度脂蛋白对心脏保护作用最强的能力是有限的，因为很难将不同类型的颗粒彼此分开。我们知道的一件事是，高密度脂蛋白的心脏保护特性和新陈代谢受到它们所含蛋白质的影响。关于两种主要的高密度脂蛋白对高密度脂蛋白新陈代谢和心脏保护特性的影响，人们已经有了相当多的了解。然而，高密度脂蛋白含有其他几种蛋白质，这些蛋白质在这方面也很重要。该项目涉及另一种名为载脂蛋白E的蛋白质，载脂蛋白E预防心脏病的证据是无可争议的。尽管如此，人们对它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有载脂蛋白E的高密度脂蛋白。为了克服这些问题，我开发了一种新的方法来制备含有载脂蛋白E的高密度脂蛋白，这些制剂可以与人血浆中含有载脂蛋白E的高密度脂蛋白相媲美。它们将用于研究载脂蛋白E对高密度脂蛋白代谢的影响。

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.