The role of apolipoprotein E in high density lipoprotein metabolism

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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.