Controlling inflammation that arises in atherosclerosis and after a stent

Regulation of anti-inflammatory gene expression in vascular endothelial cells by EPAC1

Dr Stephen Yarwood is studying ways to combat chronic inflammation, a key part of heart and circulatory disease. In conditions like atherosclerosis, when blood vessels narrow with fatty plaques, chronic inflammation causes excessive leakiness and more white blood cells attach to the vascular endothelial cells lining the blood vessels. This causes long term damage, including blocked arteries and blood clots, which can lead to heart attacks or strokes. Inflammation can also lead to restenosis, when the artery re-narrows after it has been widened using a stent. In chronic blood vessel inflammation, blood levels of inflammatory messengers, or cytokines, rise – particularly a cytokine called interleukin 6 (IL-6). Dr Yarwood has discovered that activating the enzyme EPAC1 ultimately suppresses IL-6 and prevents this inflammatory activity in vascular endothelial cells. In this project, they will determine exactly how recruiting EPAC1 to the central hub of the cell, the nucleus, controls genes involved in regulating inflammatory activity in these cells. This research could identify new ways to prevent inflammation and combat deadly heart and circulatory diseases such as atherosclerosis and restenosis.