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Metalloproteinases in degenerative aortic disease
1Department of Biochemistry, Charing Cross and Westminster Medical School, London.
Clinical Science (London, England : 1979)
|August 1, 1991
Summary
Connective-tissue-degrading enzymes, like gelatinase, are elevated in abdominal aortic aneurysm and atherosclerosis, contributing to medial thinning. These enzymes, including collagenase and stromelysin, are linked to aortic disease progression.
Area of Science:
- Biochemistry
- Vascular Biology
- Pathology
Background:
- Abdominal aortic aneurysm and atherosclerosis involve medial connective tissue thinning.
- Metalloproteinases are key enzymes in connective tissue degradation.
Purpose of the Study:
- Investigate the presence and activity of connective-tissue-degrading metalloproteinases in atherosclerotic, aneurysmal, and control aortic media.
- Determine the role of these enzymes in the pathogenesis of aortic diseases.
Main Methods:
- Homogenates of aortic media from patients with atherosclerosis, aneurysm, and controls were analyzed.
- Gelatinase activity was quantified, and zymography was used to identify specific gelatinases.
- Collagenase and stromelysin were detected by immunoblotting and activity assays.
Main Results:
- Gelatinase activity was significantly increased in atherosclerotic and aneurysmal aorta compared to controls.
- A specific 92 kDa gelatinase was prominent in atherosclerotic aorta, while a spectrum of activities (92-55 kDa) was observed in aneurysmal aorta.
- Collagenase and stromelysin were detected in aneurysmal aorta, with increased activity after inhibiting tissue inhibitors of metalloproteinases.
Conclusions:
- Elevated gelatinase activity, particularly from inflammatory cells at the intima, may contribute to atherosclerotic plaque formation and medial thinning.
- Secretion of collagenase, gelatinase, and stromelysin from the adventitia could accelerate connective tissue degradation in aneurysmal aorta.