It has been known for over a century that inflammatory processes play a role during the development of arteriosclerosis. As a matter of fact, our group has shown that the very first stage of arteriosclerosis consists in the migration of cells of the immune system into the inner layers of arteries well before fatty streaks or arteriosclerotic plaques emerge. Further scrutiny of this phenomenon, both in experimental animals and in humans, revealed that the immune system recognizes a certain type of so-called stress proteins, collectively also designated as heat shock proteins (HSPs), on the surface of endothelial cells that form the innermost lining of blood vessels.

HSPs are phylogenetically very old molecules produced by all living cells when they are subjected to stress. Thus, a stess protein termed HSP60 that is found in all organisms, from bacteria to humans, shows a very similar chemical structure. Since everybody has protective immunity against microbial HSP60, the appearance of HSP60 on stressed human cells may lead to a “confusion” of the immune system recognizing the body’s own HSP60 as foreign and thus attacking cells producing this molecule.

We have shown that classical arteriosclerosis risk factors, such as hypertension, high blood cholesterol levels, smoking, etc. lead to the expression of HSP60 by arterial endothelial cells entailing an attack of the immune system on the body’s own arteries that finally leads to the above mentioned initial inflammatory, still reversible, stage of arteriosclerosis.

The aim of the group of Georg Wick in Innsbruck is to prevent the immune system from reacting against those parts of the HSP60 molecule (so called epitopes) that are involved in the pathogenesis of arteriosclerosis. This will be achieved by developing appropriate vaccination strategies, i.e. applying HSP60 and fragments thereof to mice via the nasal or oral route, a process that is known to make the immune system tolerant against this material. It is the goal of TOLERAGE to successfully develop such a vaccine in experimental animals to a stage where this approach can subsequently be translated into use in humans.