Molecular mechanisms in cholesterol export.

动脉粥样硬化是一种使动脉变窄的疾病，会导致心脏病发作和中风。它是澳大利亚人死亡的主要原因之一。虽然某些治疗方法，如降低血液胆固醇水平，可以减少动脉粥样硬化的发病率，但目前这种疾病的死亡率表明，我们仍然非常需要提高对这种疾病的理解和治疗。在动脉粥样硬化的发展过程中，血管壁的一些细胞积聚了大量的胆固醇。这些细胞是巨噬细胞，来源于迁移到血管壁的循环白细胞。正常情况下，这些细胞能够有效地输出多余的胆固醇，但在动脉粥样硬化中，这一过程似乎失败了。本项目将研究巨噬细胞输出胆固醇的分子机制，重点研究最近发现的胆固醇泵的运作机制。它们位于细胞膜上，包括细胞表面，这是胆固醇转移到HDL和apoAI等受体的地方。通过了解这些泵是如何工作的，以及它们的活动是如何被控制的，我们将能够更好地设计出提高它们在动脉粥样硬化中的效率的方法，从而防止导致这种疾病的组织胆固醇积累。

Atherosclerosis is the disease which narrows arteries and causes heart attacks and stroke. It is one of the major causes of death in Australia. Although certain treatments, such as lowering blood cholesterol levels, reduce the incidence of atherosclerosis, current motality rates from this disease indicate that there is still a great need to improve our understanding and treament of the condition. In the development of atherosclerosis, some of the cells in the vessel wall accumulate large deposits of cholesterol. These cells are macrophages, derived from circulating white blood cells that have migrated into the vessel wall. Normally these cells are able to efficiently export excess cholesterol, but this process seems to fail in atherosclerosis. This project will study the molecular mechanism for cholesterol export from macrophages, concentrating on a the mechnisms by which recently identified cholesterol pumps operate. These are located in cell membranes, including at the cell surface, which is the site at which cholesterol is transferred to acceptors such as HDL and apoAI. By understanding how these pumps work, and how their activities are controlled, we will be better able to devise ways to increase their efficiency in atherosclerosis, and so to prevent the tissue cholesterol accumulation that drives this disease.