A potential new anti-oxidant approach to combating atherosclerosis

Lysosomal oxidation of low density lipoprotein causes inflammation in atherosclerosis

Researchers will investigate a potential new way to prevent the damaging effects of LDL cholesterol in arteries. ‘Bad’ LDL cholesterol contributes to artery disease, known as atherosclerosis, which causes heart attacks. Part of the process is that LDL cholesterol is ‘oxidised’ – becoming rancid – in the artery walls, which causes damaging inflammatory proteins to build up. Anti-oxidants have been tested as potential treatments for heart disease, but with disappointing results. These researchers have made a discovery that could explain why anti-oxidants haven’t worked in the past, and will investigate a new approach. It was thought that LDL cholesterol can be oxidised outside of cells, but Professor Leake has found that oxidation may instead take place inside ‘bags’ called lysosomes within cells called macrophages. This could be why anti-oxidant treatments haven’t worked in the past. However, one anti-oxidant treatment called cysteamine, accumulates in lysosomes. The treatment has potential: it is already used for people with a rare disease of lysosomes, and researchers have found it can reduce atherosclerosis in mice. In this grant the team will investigate the biological processes that take place after LDL cholesterol is oxidised in lysosomes, and if cysteamine can combat them. This will add to knowledge of how cysteamine acts. Hopefully it will pave the way for trials to see if it could help to protect against atherosclerosis and heart attacks in people.