Atherosclerosis has been identified as an arterial immuno-inflammatory disease. It is a progressive process that can lead to severe clinical manifestations, including sudden death, myocardial infarction and stroke.
These acute events are manly due to atherosclerotic plaque rupture or erosion, a phenomenon known as "plaque instability". The atherosclerotic plaque is an accumulation of scar tissue, blood cells, cholesterol, and other fatty substances into the artery wall. The build-up of plaque narrows the arteries and slows the flow of blood. The plaque instability is the main cause of arterial thrombus (blood clot) formation leading to coronary artery occlusion and heart attack. Advanced and stable atherosclerotic plaques are very different from the unstable ones. The former have a thick fibrous cap, rich in collagen and smooth muscle cells, while the latter show a very thin fibrous cap with inflammatory infiltrate that covers a large lipid core.

^{narrowing of vessel lumen due to build up of atherosclerotic plaque}

The aim of this programme is to understand which differences lead to the formation of unstable plaque. To reach their goal the EVGN researchers are studying new animal models to be used to clarify the mechanism of plaque rupture, to improve in vivo detection of plaques and to identify molecular targets helpful to limit progression or inhibit atherosclerotic plaque instability.

Martin R. Bennet and Mat J. Daemen, from Addenbrookes in Cambridge and from Cardiovascular Research Institute of Maastricht respectively, have the responsibility to coordinate the working groups involved in this research field.

Two of them are specifically dedicated to the identification of the genes involved in the atherosclerotic plaque instability and in the inflammatory process. In particular, the people who are working in one of these teams want to find which genes correspond to a stable plaque and which genes correspond to an unstable one. The most advanced genomics and proteomics techniques are available to the scientists involved in this research.

The focus of another workin group is to develop a mouse model for atherosclerotic plaque rupture, which can be used in studies focused on the evaluation of different therapies efficacy. Both conventional pharmacological strategies and innovative gene therapies will be screened.

Two other groups are dedicated to understanding the role of innate and adaptive immunity in atherosclerosis. The scientists want to find out which is the role of specific population of T and B cells (lymphocyte ) using the mouse model developed by other groups. Furthermore, they intend to develop new strategies aimed at preventing atherosclerotic plaque development and promoting plaque stabilization.

The last working group of this section is more clinically-oriented. Working in close cooperation with the previous ones, this team is focused on designing improved tools for diagnosis and therapeutic intervention in patients at risk of acute ischemic cardiovascular disease.