There was a large audience and stimulating presentations in this Basic Science Track symposium.
Dr G Wick (Innsbruck) presented clinical evidence on the role of heat shock proteins (HSP). HSP are known to have been conserved for more than 2.5 billion years and, more recently, it has been demonstrated that certain important HSP, such as HSP-60, participate in the immuno-inflammatory process of Atherosclerosis. Recent data suggest that traditional cardiovascular risk factors, such as smoking, might influence and activate some of these HSP in men and in women, and produce more evidence about the implications of the innate immune system during the process of Atherosclerosis.
Dr Z Mallat (Paris) explained the biological roles of activated lymphocytes at the cellular and molecular levels. Within the vascular Atherosclerotic lesion, activated T lymphocytes can secrete pro- and anti-inflammatory molecules. Basically, Th1 lymphocytes secrete pro-inflammatory cytokines such interferon-gamma, and Th2 lymphocytes anti-inflammatory cytokines, such as Interleukin-10 or TGF-beta. Recently, a new sub-type of lymphocyte, named T-regulatory lymphocyte, has been shown to participate in, and even induce, Atheroprotection in mice. One of the important issues now will be to identify strategies to expand the number of active T-regulatory lymphocytes at sites of atherosclerotic lesions.
Dr J Nilsson (Malmo) described the rational for developing a vaccine against atherosclerosis. As the first initial step of atherogenesis always starts with oxidized LDL, the development of a vaccine against ox-LDL began some years ago. Indeed, it has recently been shown that immunisation with recombinant human IgG (directed against a specific epitope of ox-LDL) protects mice from either the development and also the progression (possibly more important) of atherosclerosis, with even regression of lesions. These effects are probably mediated via an increase in the reverse cholesterol transport (increase of ABCA-1), and a decrease in MCP-1 (a major molecule for attraction and activation of leukocytes). As the oxidized LDL antigen is almost the same in mice and humans, this type of vaccine could be used in humans. Before this happens, however, concerns about possible side effects need to be resolved.
Will this vaccine induce immune complexes?
Could some effects be pro-Atherogenic?
What about the need of possible repeated immunisation?
The first human protocol with this vaccine will be tested for safety in 2007 and, hopefully, clinical studies will start in 2008.