Modulation of cell phospholipids and membranes by 7-ketocholesterol and their role in cholesterol efflux.

在澳大利亚，动脉粥样硬化是主要的死亡原因。这种疾病是由主要血管壁上形成大量胆固醇沉积引起的。这种胆固醇来自血液中携带胆固醇的颗粒，这些颗粒渗透到血管组织中。它们被组织中的细胞吸收，组织中充斥着大量的胆固醇，被称为“泡沫细胞”。这些泡沫细胞还含有少量但数量可观的受损(氧化)形式的胆固醇，称为氧化类固醇。我们已经发现，一种名为7-酮胆固醇的氧化类固醇会使细胞难以清除多余的胆固醇。因此，这种氧固醇可能是泡沫细胞发育的部分原因。这个项目将研究7-酮胆固醇如何阻止细胞中胆固醇的去除。这可能会导致药物的开发，以消除或防止7-酮胆固醇在血管中积聚，从而预防或逆转动脉粥样硬化。

Atherosclerosis is a leading cause of death in Australia. The disease is caused by the formation of large deposits of cholesterol in the walls of major blood vessels. This cholesterol comes from cholesterol-carrying particles in the blood which penetrate into the tissue of the blood vessel. They are taken up by the cells of the tissue which become engorged with large amounts of cholesterol and are called 'foam cells'. These foam cells also contain a small but signficant amount of damaged (oxidised) forms of cholesterol, called oxysterols. We have found than an oxysterol called 7-ketocholesterol makes it difficult for cells to get rid of excess cholesterol. Therefore this oxysterol may be part of the reason why foam cells develop. This project will study how 7-ketocholesterol blocks cholesterol removal from cells. This may lead to the development of drugs which remove or prevent 7-ketcholesterol accumulation in the blood vessel and so prevent or reverse atherosclerosis.