Cathepsin K gene disruption does not affect murine aneurysm formation

Lili Bai, Linda Beckers, Erwin Wijnands, Suzanne P. M. Lutgens, M. Veronica Herias, Paul Saftig, Mat J.A.P. Daemen, Kitty Cleutjens, Esther Lutgens, Erik A. L. Biessen, Sylvia Heeneman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Web of Science)

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, weinvestigated 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.
Original languageEnglish
Pages (from-to)96-103
JournalAtherosclerosis
Volume209
Issue number1
DOIs
Publication statusPublished - Mar 2010

Keywords

  • Cathepsin K
  • Aneurysm
  • Elastolytic capacity
  • Collagenolytic activity
  • Angiotensin II

Cite this