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Activated forms of MMP2 and MMP9 in abdominal aortic aneurysms
N Sakalihasan1, P Delvenne, B V Nusgens
1Department of Cardiovascular Surgery, CHU Sart Tilman, University of Liège, Belgium.
Purpose:
This consistent observation of a reduction of the elastin concentration in abdominal aortic aneurysms (AAAs) has led us to investigate in AAA specimens two metalloproteinases that display elastase activity, MMP2 (gelatinase A/72kDa) and MMP9 (gelatinase B/92 kDa).
Methods:
Samples of full-thickness aortic wall, adherent thrombus, and serum were collected in 10 patients with AAAs. Samples of normal aortic wall and serum were taken from 6 age-matched control patients. Quantitative gelatin-zymography and gelatinolytic soluble assays after acetyl-phenyl mercuric acid activation were performed on serum and tissue extracts, and the results were expressed in units on a comparative wet-weight basis. Histologic analysis was performed in parallel to score the inflammatory infiltrate.
Results:
The luminal and parietal parts of the thrombus contained, respectively, 20- and 10-fold more gelantinolytic activity than the serum. The predominate form was MMP9. Although the total gelatinolytic activity was in the same range both in AAAs and in normal walls, a significantly higher proportion of MMP9 was found in the aneurysmal aortic walls. Furthermore, a significant proportion of MMP9 was under its processed active form, which was never observed in normal samples. A significantly higher proportion of MMP2 was also present as processed active form in AAA wall. This latter parameter positively correlated with the inflammatory score.
Conclusions:
The presence of activated MMP9 and MMP2 might contribute to the degradation of the extracellular matrix proteins that occurs during the development of aneurysms.
Insights
Activated matrix metalloproteinases (MMPs), specifically MMP9 and MMP2, are elevated in abdominal aortic aneurysms (AAAs), suggesting their role in extracellular matrix degradation during AAA development.
Area of Science:
- Biochemistry
- Vascular Biology
- Pathology
Background:
- Abdominal aortic aneurysms (AAAs) are characterized by reduced elastin concentration.
- Metalloproteinases (MMPs) with elastase activity are implicated in AAA pathogenesis.
Purpose of the Study:
- To investigate the role of matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) in abdominal aortic aneurysm (AAA) specimens.
- To quantify gelatinolytic activity and identify active forms of MMP2 and MMP9 in AAA tissue.
Main Methods:
- Collected aortic wall, thrombus, and serum samples from AAA patients and controls.
- Utilized quantitative gelatin-zymography and soluble assays for MMP activity.
- Performed histological analysis to assess inflammatory infiltrate.
Main Results:
- Gelatinolytic activity was significantly higher in AAA thrombus compared to serum.
- A higher proportion of MMP9, particularly its active form, was found in AAA walls versus normal walls.
- Processed active forms of MMP2 and MMP9 were elevated in AAA walls, with MMP2 correlating with inflammation.
Conclusions:
- Activated MMP9 and MMP2 are present in AAA tissues.
- These activated enzymes may contribute to the degradation of extracellular matrix proteins in AAA development.