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Updated: Jun 20, 2026
Creation of Murine Experimental Abdominal Aortic Aneurysms with Elastase
Published on: July 23, 2009
Cathepsin K gene disruption does not affect murine aneurysm formation
Lili Bai1, Linda Beckers, Erwin Wijnands
1Experimental Vascular Pathology Group, Department of Pathology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, P. Debyelaan 25, Maastricht, The Netherlands.
Insights
Cathepsin K (catK) deficiency did not prevent abdominal aortic aneurysm formation in mice. Compensatory proteases and increased collagen content suggest complex roles in vascular disease.
Area of Science:
- Biochemistry
- Vascular Biology
- Protease Function
Background:
- Cathepsin K (catK), a protease, is implicated in cardiovascular diseases and elevated in human aortic aneurysms.
- Angiotensin II (Ang II) infusion upregulates catK, S, and C expression in a mouse model of aneurysm formation.
Purpose of the Study:
- To investigate the effect of catK deficiency on Angiotensin II-induced abdominal aortic aneurysm formation in apoE-/- mice.
Main Methods:
- Utilized a mouse model (apoE-/-) subjected to Angiotensin II infusion.
- Assessed aneurysm formation, medial elastin breaks, proteolytic activity, and collagen content in wild-type and catK-deficient mice.
- Quantified circulating immune cells and adventitial leukocyte content.
Main Results:
- Cathepsin K deficiency did not protect against aneurysm formation or affect medial elastin breaks.
- Proteolytic activity in aortic lysates was comparable between groups.
- Increased presence of catS- and catC-expressing cells was observed in catK-deficient mice.
- Collagen content was significantly increased in aneurysms of catK-deficient mice despite unchanged proteolytic activity.
Conclusions:
- Cathepsin K deficiency does not influence Angiotensin II-induced murine abdominal aortic aneurysm formation.
- Upregulation of other cathepsins (S and C) may compensate for catK deficiency.
- Increased collagen content in catK-deficient aneurysms warrants further investigation into protease roles in vascular remodeling.
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.
