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

High Molecular Weight Kininogen acts as an anti-apoptotic factor in vascular smooth muscle cells

Hochmolekulares Kininogen fungiert als antiapoptotischer Faktor in glatten Gefäßmuskelzellen

Meeting Abstract

Suche in Medline nach

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

Hypertonie 2005. 29. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Berlin, 23.-25.11.2005. Düsseldorf, Köln: German Medical Science; 2006. Doc05hochP135

Die elektronische Version dieses Artikels ist vollständig und ist verfügbar unter: http://www.egms.de/de/meetings/hoch2005/05hoch135.shtml

Veröffentlicht: 8. August 2006

© 2006 Doerfel 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

Objectives: Apoptosis of vascular smooth muscle cells (VSMC) is known as an important factor in the pathogenesis of aortic aneurysm. The aim of our study was to investigate the role of caspases, cathepsins and the cysteine protease inhibitor, high molecular weight kininogen (HMWK), in VSMC apoptosis.

Methods: Primary VSMC were isolated via enzyme digestion from aortae of male Wistar rats, Brown Norway (BN), which develop aortic lesions and Brown Norway Katholiek (BN/Ka), known to be genetically kininogen deficient. Apoptosis was induced via NO, FasL, cytokines TNF-alpha, Interferon-gamma and Interleukin-1alpha for 24 hours. Cleaved caspase 3 served as a marker for successful apoptosis induction. Protein expression of caspases, cathepsins, Fas receptor and kininogen were investigated in Western Blot analysis and activity assay. The influence of HMWK on the apoptotic cascade was investigated by simultaneous stimulation together with single chain HMWK (1 nM, 10 nM, 50 nM, 100 nM).

Results: 24 hours after apoptosis induction, cathepsin B was upregulated (5-fold) and cathepsin D was down-regulated (2-fold). Death receptor Fas showed no changes. Screening of the caspases cascade showed up-regulation of the caspases 6,8 and 9 in cells from BN/Ka compared to BN. After apoptosis induction the heavy chain of HMWK was down-regulated strongly in cells of all rat strains. After adding single chain HMWK (10 nM) to the stimulation cocktail the active cleaved caspase 3 form was down-regulated to control levels.

Conclusion: These data support the hypothesis that kininogen participates in apoptotic process as an anti-apoptotic factor.