Molecular mechanisms in cholesterol export.

动脉粥样硬化是一种导致动脉狭窄、心脏病发作和中风的疾病。这是澳大利亚的主要死亡原因之一。虽然某些治疗，如降低血液胆固醇水平，降低动脉粥样硬化的发病率，目前的死亡率从这种疾病表明，仍然有很大的需要，以提高我们的理解和治疗的条件。在动脉粥样硬化的发展过程中，血管壁中的一些细胞积累了大量胆固醇沉积物。这些细胞是巨噬细胞，来源于迁移到血管壁中的循环白色血细胞。正常情况下，这些细胞能够有效地输出多余的胆固醇，但这一过程似乎在动脉粥样硬化中失败了。本项目将研究巨噬细胞中胆固醇输出的分子机制，重点是最近发现的胆固醇泵的运作机制。这些位于细胞膜中，包括在细胞表面，这是胆固醇转移到受体如HDL和apoAI的位点。通过了解这些泵如何工作，以及它们的活动是如何控制的，我们将能够更好地设计方法来提高它们在动脉粥样硬化中的效率，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.