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Trigger of heart attack found in immune system

(Vienna, 6 October 2010) Normally the human immune system protects the organism against infections but can, in exceptional cases, also damage healthy cells. In an evolutionarily very old part of our immune system, the complement system, scientists of MedUni Vienna have now been able to prove such a component. This work, which is of relevance for novel therapeutic approaches, was recently also published in the renowned medical journal "The FASEB Journal".

The human complement system forms part of the innate immune system and is therefore among the body's oldest methods to protect itself against invading microorganisms. Today it still represents the first defence line against bacteria. Dr. Walter Speidl and Dr. Stefan Kastl from the scientific team headed by Ao. Univ. Prof. Dr. Johann Wojta at the Clinical Division of Cardiology (Department of Medicine II) in cooperation with specialists from Germany and the US have been able to prove that one component of this complement system, the anaphylatoxin C5a, has a major impact on the development of acute cardiovascular events such as heart attack or stroke.

For the study, certain immune cells (macrophages) from vessel wall calcifications, so-called atherosclerotic plaques, were isolated and treated with the protein C5a, which originates in the complement system. This treatment led to an increased production of matrix metalloproteinases (MMP-1 and MMP-9). These are proteins which due to tissue degradation between cells (extracellular matrix) can lead to the rupture of the atherosclerotic plaques and therefore to acute vascular occlusion.

Furthermore, the study show that C5a jointly with these metalloproteinases could be found in the coronary arteries of patients with heart attack, whereas it was not found in the vessels of patients with a stable coronary heart disease without heart attack. Thanks to the findings of this study, which has met with wide international acclaim, the complement component C5a has been identified as a possible new target for the prevention and treatment of heart attacks and strokes.

Says Speidl about the findings: "Heart attacks and strokes are the most frequent cause of death for us Austrians. One third of our patients with a heart attack shows none of the classic risk factors such as smoking or elevated concentrations of blood lipids. Over recent years we have shown in several studies that elevated C5a-levels in the blood lead to an increased risk of heart attack, stroke and the reocclusion of vessels."

Adds Kastl: "In our previous works we have already been able to show connections between the complement system and the formation of blood clots. The trials have now identified C5a as one possible trigger for acute heart attack."

Wojta about the new therapeutic options: "To date it has only been possible to treat risk factors for vessel calcifications. But it has not been possible to treat the plaques directly by means of medication. After the discovery of C5a as one possible trigger of heart attack and stroke there is now a new target for the development of a direct, causal therapy.“

» Publication in The FASEB Journal:
Walter S. Speidl, Stefan P. Kastl, Randolph Hutter, Katharina M. Katsaros, Christoph Kaun, Gerhard Bauriedel, Gerald Maurer, Kurt Huber, Juan J. Badimon, and Johann Wojta
The complement component C5a is present in human coronary lesions in vivo and induces the expression of MMP-1 and MMP-9 in human macrophages in vitro
FASEB J. published Sep 2, 2010, doi:10.1096/fj.10-156083

Short biography:
Ao. Univ. Prof. Dr. Johann Wojta, born in 1957, has been employed at the Medical University (formerly Medical Faculty of the University of Vienna) since 1983, where he also qualified as a professor in 1990. Since 1998 he has headed the research laboratory of the Clinical Division of Cardiology at the Department of Medicine II, since 2009 he has been the coordinator of the Ludwig Boltzmann cluster for cardiovascular research and since 2010 coordinator of Anna Spiegel Centre of Translational Research at MedUni Vienna.
Within the framework of his teaching activities, Wojta not only holds various lectures but also initiated a medical traineeship programme for Austrian physicians in cooperation with three partner universities in Australia in 1995.
He has obtained numerous grants as well as national and international awards for his research and has published more than 160 publications in a large number of medical journals. In addition Wojta is active not only as a reviewer for many of these journals but also for national and international grants. He also fulfils different tasks in scientific societies of which he is a member.