gms | German Medical Science

29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Hochdruckliga e. V. DHL ® - Deutsche Hypertonie Gesellschaft Deutsches Kompetenzzentrum Bluthochdruck

23. bis 25.11.2005, Berlin

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

Meeting Abstract

Suche in Medline nach

  • U. Vosgerau - Charité - Universitätsmedizin Berlin Center for Cardiovascular Research (Berlin, D)
  • T. Unger - Charité - Universitätsmedizin Berlin Center for Cardiovascular Research (Berlin, D)
  • E. Kaschina - Charité - Universitätsmedizin Berlin Center for Cardiovascular Research (Berlin, D)

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP85

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2005/05hoch085.shtml

Veröffentlicht: 8. August 2006

© 2006 Vosgerau et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielf&aauml;ltigt, verbreitet und &oauml;ffentlich zug&aauml;nglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

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.