Artikel
Two-chain high molecular weight kininogen is involved in the regulation of MMP-2 and MMP-9 expression in vascular smooth muscle cells
Gespaltenes Kininogen ist an der Regulation von MMP-2 und MMP-9 in glatten Gefäßmuskelzellen beteiligt
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Autoren
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U. Vosgerau
- Charité - Universitätsmedizin Berlin Center for Cardiovascular Research (Berlin, D)
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T. Unger
- Charité - Universitätsmedizin Berlin Center for Cardiovascular Research (Berlin, D)
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E. Kaschina
- Charité - Universitätsmedizin Berlin Center for Cardiovascular Research (Berlin, D)
| Veröffentlicht: | 8. August 2006 |
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Gliederung
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Objektives: Increased activity of matrix metalloproteinases (MMPs) in the aortic wall, leading to degradation of extracellular matrix components, plays a crucial role in aneurysm formation. We have recently shown that rats lacking high molecular weight kininogen develop aortic aneurysm, associated with an increased activity of MMPs. We investigated if two-chain high molecular weight kininogen (HKa), the cleavage product of high molecular weight kininogen lacking the bradykinin moiety, is involved in the regulation of MMP-2 and MMP-9 expression.
Methods: Vascular smooth muscle cells (VSMC) were cultured from the abdominal aorta of Wistar rats. VSMC were stimulated for 48h with Interleukin-1alpha (IL-1alpha , 10 ng/ml). Simultaneously, the IL-1alpha stimulation was performed together with HKa (10 nM, 100 nM, 1 µM). Expression of MMP-2 and MMP-9 were analyzed by gelatin zymography and Western blotting.
Results: IL-1 alpha stimulation increased MMP-2 expression (1.8 fold vs. control) and induced MMP-9 expression. The expression levels of MMP-2 and MMP-9 were significantly decreased by HKa 1µM (29 % and 32% respectively).
Conclusions: Two-chain high molecular weight kininogen decreases MMP-2 and MMP-9 expression induced by Interleukin-1alpha in VSMC. These data demonstrate that two-chain high molecular weight kininogen is involved in the regulation of MMPs. Furthermore, these data support the hypothesis that kininogen deficiency leads to up-regulation of MMPs contributing to aneurysm formation.
