More than half of all deaths in Europe are caused by cardiovascular disease, and 80% of all these are due to atherosclerosis. Repairing a heart after a myocardial infarction by an infusion of progenitor cells and developing a vaccination against atherosclerosis are two of the main objectives of EVGN, the network of excellence in vascular biology that has been at the forefront of European research in this field.
The trial to regenerate damaged heart tissue and restore cardiac function involved a number of European hospitals. The progenitor cells were isolated from the bone marrow of patients who had suffered from a recent acute myocardial infarction and reintroduced into the same donor’s organism. The achievements of the double blind EVGN trial in Frankfurt and Zuerich were later described as “extremely encouraging”, namely a considerable improvement of the cardiac pump function. After 4 months the clinicians observed a neat recovery in the performance of the left ventricule, that could eject a bigger flux of blood”.
In addition, the Frankfurt and Zuerich patients who received the therapeutic cells showed a marked positive effect on the remodeling process of the cardiac tissue and an improvement in the growth of new blood vessels within the infarct area. This was especially beneficial in patients with a vaster myocardial infarction.
The other big topic of EVGN (European Vascular Genomics Network), such as the development of a vaccination against atherosclerosis, presupposes that the immune system is involved in the process. In this case, scientist need to create a counterimmunity to block or slow down the development of the disease.
At a previous EVGN conference, scientists had described a new model of atherosclerosis development, suggesting that this pathology might result from an imbalance between inflammatory and anti-inflammatory processes which would then lead to blood clot formation and heart attacks. The inflammatory process acts like a kind of alarm bell indicating the onset of atherosclerosis.
A joint EVGN effort allowed to identify a subpopulation of T lymphocites (also called natural T regulatory cells, or Treg), which inhibit the formation of atherosclerotic plaques. EVGN coordinator, Professor Alain Tedgui, together with Dr. Ziat Mallat of INSERM in Paris and Dr. Goran Hansson of the Karolinska Institute’s Centre for Molecular Medicine in Stockholm led two of the research teams in the study, which postulates that in atherosclerosis there is an imbalance between regulatory and pathogenic immunity, promoting both plaque development and inflammation. In a mouse model, scientists noticed the animals without Tregs developed bigger atherosclerotic lesions. But the Tregs, when injected, could turn off the atherosclerotic process.
EVGN scientists went one step further and also identified a signaling molecule, called TGF-beta, which is made by Treg and inhibits atherosclerosis. By turning it off with gene technology, scientists noticed that Treg cells lost their protective ability and concluded that TGF-beta is an important tool by which Treg cells defend the body against atherosclerosis. Although it might still be early days, it seems now reasonable to Professor Tedgui to start thinking about novel kinds of therapies based on regulatory immune cells.
(11 November 2009)