Cathepsin K gene disruption does not affect murine aneurysm formation

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.