Cathepsin K gene disruption does not affect murine aneurysm formation

被引：23

作者：

Bai, Lili ^{[1
]}

Beckers, Linda ^{[1
]}

Wijnands, Erwin ^{[1
]}

Lutgens, Suzanne P. M. ^{[1
]}

Herias, M. Veronica ^{[1
]}

Saftig, Paul ^{[2
]}

Daemen, Mat J. A. P. ^{[1
]}

Cleutjens, Kitty ^{[1
]}

Lutgens, Esther ^{[1
]}

Biessen, Erik A. L. ^{[1
,3
]}

Heeneman, Sylvia ^{[1
]}

机构：

[1] Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht, Dept Pathol,Expt Vasc Pathol Grp, NL-6229 HX Maastricht, Netherlands

[2] Univ Kiel, Inst Biochem, D-24098 Kiel, Germany

[3] Leiden Univ, Leiden Amsterdam Ctr Drug Res, Div Biopharmaceut, Gorlaeus Labs, NL-2333 CC Leiden, Netherlands

来源：

ATHEROSCLEROSIS | 2010年 / 209卷 / 01期

关键词：

Cathepsin K; Aneurysm; Elastolytic capacity; Collagenolytic activity; Angiotensin II; ABDOMINAL-AORTIC-ANEURYSM; MATRIX METALLOPROTEINASES; ATHEROSCLEROSIS; INFLAMMATION; DEGRADATION; DEFICIENCY; INHIBITOR;

D O I：

10.1016/j.atherosclerosis.2009.09.001

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

引用

页码：96 / 103

页数：8

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