Abstract
Cathepsin K (catK), a lysosomal cysteine protease, exerts strong elastinolytic and
collagenolytic activity and is implicated in a range of pathological disorders including
cardiovascular disease. CatK expression was found to be elevated in human aortic aneurysm
pointing to a role in this vasculopathy. In the angiotensin II (Ang II)-induced mouse
model for aneurysm formation, catK, S and C expression was strongly upregulated. Therefore,
we investigated the effect of catK deficiency on Ang II-induced aneurysm formation
in the abdominal aorta of apoE−/− mice.
Contrary to our expectations, catK deficiency did not protect against aneurysm formation,
nor did it affect medial elastin breaks. Proteolytic activity in abdominal aortic
lysates were comparable between apoE−/− and catK−//−apoE−/− mice. Adventitial presence
of catS- and catC-expressing cells was significantly increased in catK−/−//apoE−/−
versus apoE−/− mice, which might have compensated for the deficiency of catK-derived
proteolysis in the aneurysm tissue of catK deficient apoE−/− mice. Circulating granulocytes
and activated T cell numbers were significantly increased in Ang II-infused catK−/−//apoE−/−
mice, which is consistent with the borderline significant increase in adventitial
leukocyte content in catK−/−//apoE−/− compared to apoE−/− mice. Strikingly, despite
unchanged proteolytic activity in AAA lesions, collagen content in the aneurysm was
significantly increased in catK−//−apoE−/− mice. In conclusion, while catK deficiency
has major impact on various vasculopathies, it did not affect murine aneurysm formation.
Keywords
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Article info
Publication history
Published online: September 24, 2009
Accepted:
September 1,
2009
Received in revised form:
August 27,
2009
Received:
July 15,
2009
Footnotes
☆The authors (MJAPD, KC, EALB, SH) participate in the European Vascular Genomics Network (http://www.evgn.org), a Network of Excellence supported by the European Community's Sixth Framework Program for Research Priority 1 (Life Sciences, Genomics, and Biotechnology for Health; contract LSHM-CT-2003-503254). This study was supported by grant 2003T201 from the Netherlands Heart Foundation (EALB).
Identification
Copyright
© 2009 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
