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

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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.