Cathepsin K gene disruption does not affect murine aneurysm formation.
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.
Bai
Lili
L
Experimental Vascular Pathology Group, Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, P. Debyelaan 25, Maastricht, The Netherlands.
Beckers
Linda
L
Wijnands
Erwin
E
Lutgens
Suzanne P M
SP
Herías
M Verónica
MV
Saftig
Paul
P
Daemen
Mat J A P
MJ
Cleutjens
Kitty
K
Lutgens
Esther
E
Biessen
Erik A L
EA
Heeneman
Sylvia
S
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D020789:Cathepsin C / Q000235:genetics; D056657:Cathepsin K / Q000235:genetics*; D002403:Cathepsins / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D001057:Apolipoproteins E; D000804:Angiotensin II; D003094:Collagen; D002403:Cathepsins; D020789:Cathepsin C; C533919:Ctsc protein, mouse; C028217:cathepsin S; D056657:Cathepsin K; C534132:Ctsk protein, mouse