The endothelium is a thin layer of flat smooth cells that line the inner walls of blood vessels (veins and arteries). These cells play an important role in the mechanics of blood flow. If the endothelium gets damaged, which is exactly what happens in endothelial dysfunction, the walls of the artheries may lose their elasticity and become hard and thick. This, in turn, reduces the supply of blood - with its oxygen and nutrients - to the tissues. Endothelial dysfunction has shown to play a key role in the early steps of atherosclerosis as well as in the further development of this pathological process.

Within the EVGN project, the group of Rudi Busse and Ingrid Fleming, based at the Cardiovascular Physiology Department at the University of Frankfurt, coordinates the researchers that are trying to clarify the molecular basis of endothelial dysfunction.

Endothelial dysfunction reveals itself as a specific state called “endothelial activation” which is characterized by a particular environment (proinflammatory , proliferative and pro procoagulatory ) and by an abnormal enlargement of vessels (a process that is called vasodilation). This environment favors all stages necessary for the atherosclerosis development.

The main goal of the endothelian dysfuntion group at EVGN is to understand why and how this happens. Furthermore, the researchers will try to find a way to diagnose early signs of a predisposition to develop cardiovascular disease. Last but not least, this team will try to find molecules that can serve as a target for therapeutic strategies to preserve endothelial cells.

The EVGN “endothelial dysfuntion” research group is made up of 6 different international working group, that involve several EVGN research teams, coming from different countries.

The first four working groups are focused in understanding the role of specific enzymes in the endothelial physiology alteration. The molecules under study are: endothelial NO synthase, NADPH oxidase, cytocrome P450, kallikrein-kinin and renin-agiotensin. They are all present in the endothelial cells and have a specific role in the normal blood vessel function. But sometimes these enzymes can work badly, or can be present in too high or too low concentrations: in these cases the cells go toward an abnormal condition leading to endothelial dysfunction.

The aim of the fifth working group is to identify genetic differences between patients with coronary artery disease and healthy subjects. The team that works in this group is clinically-oriented and it has to collect a large number of blood samples to work on. In particular, the researchers are trying to find the little variations in genes (polymorphisms) associated with endothelial dysfunction.

The sixth working group studies the action of the microparticles that are shed from the membrane of activated endothelial cells. These particles are thought to play an important role in atherosclerotic plaque development: previous studies have shown the accumulation of the microbodies within the plaque and guessed their presence in the vessels during ischemic events . Once they are formed, the microparticles induce the cells to a progressive process, known as apoptosis , leading to cell death. The EVGN scientists want to clarify this mechanisms in order to identify enzymes and other molecules that can serve as potential target for developing new therapeutic strategies