Loss of matrix metalloproteinase-9 or matrix metalloproteinase-12 protects apolipoprotein E-deficient mice against atherosclerotic media destruction but differentially affects plaque growth

Article

关键词: ABDOMINAL AORTIC-ANEURYSMS;    SMOOTH-MUSCLE-CELLS;    TISSUE INHIBITOR;    GENE;    ANGIOGENESIS;    OVEREXPRESSION;    OSTEOPONTIN;    DISRUPTION;    MIGRATION;    RUPTURE;   

DOI  :  10.1161/01.CIR.0000121728.14930.DE

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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