Abstract
Background - Epidemiological and histological evidence implicates proteinases of the matrix metalloproteinase (MMP) family in atherosclerosis and aneurysm formation. We previously indicated a role for urokinase-type plasminogen activator in atherosclerotic media destruction by proteolytic activation of MMPs. However, the role of specific MMPs, such as MMP-9 and MMP-12, in atherosclerosis remains undefined. Methods and Results - MMP-9- or MMP-12-deficient mice were crossed in the atherosclerosis-prone apolipoprotein E-deficient background and fed a cholesterol-rich diet. Mice were killed at 15 or 25 weeks of diet to study intermediate and advanced lesions, respectively. Loss of MMP-9 reduced atherosclerotic burden throughout the aorta and impaired macrophage infiltration and collagen deposition, while MMP-12 deficiency did not affect lesion growth. MMP-9 or MMP-12 deficiency conferred significant protection against transmedial elastin degradation and ectasia in the atherosclerotic media. Conclusions - This study is the first to provide direct genetic evidence for a significant involvement of MMP-9, but not of MMP-12, in atherosclerotic plaque growth. In addition, deficiency of MMP-9 or MMP-12 protected apolipoprotein E-deficient mice against atherosclerotic media destruction and ectasia, mechanisms that implicate the involvement of these MMPs in aneurysm formation.
Original language | English (US) |
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Pages (from-to) | 1408-1414 |
Number of pages | 7 |
Journal | Circulation |
Volume | 109 |
Issue number | 11 |
DOIs | |
State | Published - Mar 23 2004 |
Keywords
- Aneurysm
- Atherosclerosis
- Collagen
- Hypercholesterolemia
- Metalloproteinases
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)