For decades, doctors have looked at fitness levels, weight, and overall health risk factors for heart disease and stroke. Now, they may soon add a new risk factor to the list: activation of the complement system. The complement system is usually implicated in immune responses, but now there's a role for it in cardiovascular disease. In a new research report appearing in the January 2011 print issue of the FASEB Journal (http://www.
"Given the huge impact of cardiovascular disease in general, and atherosclerosis in particular, on public health, we feel that unraveling mechanisms involved in the development and progression of the disease are of utmost importance," said Johann Wojta, Ph.D., a researcher involved in the work from the University of Vienna in Austria. "Our findings have identified a particular component possibly involved in the development of atherosclerosis as a target for future therapies."
To make this discovery, Wojta and colleagues treated white blood cells with the C5a. In turn, these cells responded with the production of specific enzymes capable of dissolving the inner wall of atherosclerotic plaques in coronary or brain vessels. This causes the plaques to rupture, break free from where they are anchored, and ultimately create a blockage of the vessels, leading to the development of more serious problems such as heart attacks or strokes. The researchers also showed that C5a was present in blood vessels of patients with myocardial infarction, but not in cardiac patients without infarct. This suggests that inhibiting C5a might provide a therapeutic tool in the prevention or treatment of atherosclerosis, as well as other diseases with immune system participation such as arthritis.
"Up to now, anaphylatoxin C5a has been mainly implicated in immunologic diseases such as asthma, rheumatoid arthritis or lupus," said Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "But now, this study shows that C5a, a product of an activated complement system may be responsible for the devastating effects of atherosclerosis."
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FASEB comprises 23 societies with more than 100,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB enhances the ability of scientists and engineers to improve--through their research--the health, well-being and productivity of all people. FASEB's mission is to advance health and welfare by promoting progress and education in biological and biomedical sciences through service to our member societies and collaborative advocacy.
Details: 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 January 2011 25:35-44; doi:10.1096/fj.10-156083 ; http://www.