Complement Component Linked to Risk of Heart Attack or Stroke

In humans, the polypeptide contains 74 amino acids. It is a powerful inflammatory mediator, and seems to be a key factor in the development of pathology of many inflammatory diseases involving the complement system. In order to function, the C5a fragment binds to either the C5aR or CD88 receptor protein on the surface of target cells. One class of target cell is the macrophage.

Macrophages become localized in the rupture-prone shoulder regions of coronary plaques, and are thought to play a major role in plaque destabilization and rupture through the production of matrix metalloproteinases (MMPs). In the current study, investigators at the Medical University of Vienna (Austria) used immunochemical and immunohistological methods to study C5a both in macrophage cultures and in tissues removed from human coronary plaques.

They reported in the January 2011 issue of the FASEB Journal that when human monocyte-derived macrophages were stimulated in vitro with C5a, MMP-1 and MMP-9 mRNA levels were significantly increased. Furthermore, C5a stimulated increased MMP-1 and MMP-9 antigens and activity. These effects were blocked by antibodies against the receptor C5aR/CD88. Analysis of human coronary plaques demonstrated the co-localization of C5a, MMP-1, and MMP-9 in vivo.

"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 senior author Dr. Johann Wojta, professor of cardiovascular research at the Medical University of Vienna. "Our findings have identified a particular component possibly involved in the development of atherosclerosis as a target for future therapies."

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Medical University of Vienna