gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Deficiency predisposes to aortic aneurysm formation via activation of elastolysis, apoptosis and proteolysis

Kininogen-Defizienz prädisponiert zur Aortenaneurysmen durch Aktivierung von Elastolyse, Apoptose und Proteolyse/Kininogen

Meeting Abstract (Hypertonie 2003)

  • presenting/speaker M. Stoll
  • M. Sommerfeld
  • R. Kreutz
  • T. Unger

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochV28

The electronic version of this article is the complete one and can be found online at:

Published: November 11, 2004

© 2004 Stoll et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



Kininogens are known to inhibit cysteine proteases which possess elastolytic activity and influence apoptosis. In the present study, we analysed the role of these mechanisms in aneurysm formation comparing kininogen deficient Brown Norway Katholiek rats (BN/Ka) with normal kininogen Brown Norway rats (BN).

Rats were proven to be inbred. A point mutation (G to A) at nucleotide 484 known to be responsible for the defective secretion of kininogens was detected in BN/Ka. At 10 weeks of age, male rats were fed an atherogenic diet for 12 weeks. The aortae were examined for aneurysms. Aortic elastin and total collagen content were demonstrated using Velocity Image System; apoptosis by in situ TUNEL staining and immunostaining for FasL. The expression of Fas-L, caspase-3, p53, Bcl-2, Bcl-xs/L, MMP-2, MMP-3, TIMP-1 and TIMP-4 was analysed by Western blot.

The increased incidence of aneurysms by BN/Ka on chow diet (cd) (2-fold) and atherogenic (ad) diet (2,5 fold) compared to BN cd, ad, respectively, was accompanied by a decreased elastin/total collagen ratio (cd: 0.5±0.03 vs 0.85±0.05; ad: 0.48±0.03 vs 0.83±0,04). An increase in apoptotic cells in aorta, heart and liver was observed in BN/Ka ad. In the aorta of BN/Ka cd, ad compared with BN cd, ad, Fas-L (2-fold), caspase-3 (3-fold), Bcl-xs/L, MMP-2, MMP-3 (2,5-fold) proteins were up-regulated, TIMP-4 strongly down-regulated (4-fold); p53 up-regulated in the heart and FasL in the liver. All differences were statistically significant (p<0.05-0.01).

Thus, genetic kininogen deficiency is associated with enhanced elastolysis, FasL and caspase-3 mediated apoptosis and the induction of the MMP-2, MMP-3 proteolytic cascade in aorta which all contribute to aneurysm formation. Kininogen deficiency also promotes apoptosis in the heart and liver.