Abstract | BACKGROUND: 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.
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Authors | Aernout Luttun, Esther Lutgens, Ann Manderveld, Katleen Maris, Désiré Collen, Peter Carmeliet, Lieve Moons |
Journal | Circulation
(Circulation)
Vol. 109
Issue 11
Pg. 1408-14
(Mar 23 2004)
ISSN: 1524-4539 [Electronic] United States |
PMID | 14993123
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Apolipoproteins E
- Collagen
- Elastin
- Metalloendopeptidases
- Matrix Metalloproteinase 9
- Matrix Metalloproteinase 12
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Topics |
- Animals
- Aortic Diseases
(enzymology, etiology, pathology)
- Apolipoproteins E
(deficiency, genetics)
- Arteriosclerosis
(enzymology, etiology, pathology)
- Collagen
(metabolism)
- Diet, Atherogenic
- Dilatation, Pathologic
- Elastin
(metabolism)
- Extracellular Matrix
(pathology)
- Female
- Hypercholesterolemia
(complications)
- Macrophages
(pathology)
- Matrix Metalloproteinase 12
- Matrix Metalloproteinase 9
(deficiency, genetics, physiology)
- Metalloendopeptidases
(deficiency, genetics, physiology)
- Mice
- Mice, Inbred C57BL
- Tunica Media
(pathology)
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