Vulnerable Atherosclerotic Plaques, Foam Cell Phenotypes & Extracellular Proteinases

Coronary heart disease is caused by obstruction of the arteries feeding the heart thanks to a build up of fatty deposits known as atherosclerotic plaques. Heart attacks are often caused by blood clots forming at the point where plaques rupture because they have become weakened by digestive enzymes called proteases. White blood cells enter plaques initially to get rid of the fatty deposits but can become trapped. Our recent work shows that white blood cells often over-produce proteases in this situation and therefore change from beneficial to harmful. This programme seeks to find ways of reversing this process and thereby prevent heart attacks.

Rag KO does not influence macrophage polarization or MMP expression during atherosclerosis. Tbet KO reduces atherosclerotic plaque size but not plaque vulnerability to rupture, as M1 polarization and related MMP expression is maintained.