Title: Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein E-deficient mice against atherosclerotic media destruction but differentially affects plaque growth
Authors: Luttun, Aernout
Lutgens, Esther
Manderveld, Ann
Maris, Katleen
Collen, Desire
Carmeliet, Peter
Moons, Lieve # ×
Issue Date: Mar-2004
Publisher: American Heart Association
Series Title: Circulation vol:109 issue:11 pages:1408-1409
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.
ISSN: 0009-7322
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Animal Physiology and Neurobiology Section - miscellaneous
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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