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Cysteine protease activity in the wall of abdominal aortic aneurysms

Said Abisi1, Kevin G Burnand, Matthew Waltham

  • 1Academic Department of Surgery, Cardiovascular Division, King's College School of Medicine, St Thomas' Hospital, London, United Kingdom.

Journal of Vascular Surgery
|December 25, 2007
PubMed

Insights

Increased activity of cysteine proteases (cathepsins B, H, L, S) and reduced cystatin C in abdominal aortic aneurysm (AAA) walls compared to aortic occlusive disease (AOD) walls suggest a role in AAA development.

Area of Science:

  • Vascular Biology
  • Enzymology
  • Pathophysiology

Background:

  • Cysteine proteases and cystatin C are implicated in abdominal aortic aneurysm (AAA) growth.
  • Previous comparisons of AAA tissue with normal aorta may be confounded by atherosclerosis.
  • This study compares cysteine proteases and inhibitors in AAA with aortic occlusive disease (AOD) to isolate aneurysm-specific changes.

Purpose of the Study:

  • To compare the expression and activity of cysteine proteases and their inhibitors in AAA wall versus AOD wall.
  • To investigate the relationship between cysteine protease activity, cystatin C levels, and matrix metalloproteinase 9 (MMP-9) activity in AAA.

Main Methods:

  • Aortic wall tissue was collected from 82 AAA patients and 13 AOD patients.
  • Protein expression and activity of cathepsins (B, H, K, L, S) and cystatins (A, B, C) were quantified.
  • Matrix metalloproteinase 9 (MMP-9) activity was also measured.

Main Results:

  • AAA wall showed significantly higher cathepsin H protein and activity for cathepsins B, H, L, and S compared to AOD wall.
  • Cystatin C levels were significantly lower in AAA wall than in AOD wall.
  • MMP-9 activity was elevated in AAA and correlated with cathepsin L activity and inversely with cystatin C.

Conclusions:

  • Elevated activity of multiple cathepsins (B, H, L, S) and reduced cystatin C in AAA walls suggest their involvement in AAA pathogenesis.
  • Post-translational modifications likely activate cathepsins, as only cathepsin H showed a correlation between protein level and activity.
  • Increased cathepsin activity may modulate MMP-9 activity, contributing to aneurysm development.
Abstract

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