Reduced Atherosclerotic Plaque but Enhanced Aneurysm Formation in Mice With Inactivation of the Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) Gene
作者： J. Silence , D. Collen , H.R. Lijnen
DOI: 10.1161/01.RES.0000016501.56641.83
关键词:
摘要: Development and progression of atherosclerotic lesions aneurysm formation were investigated in mice with single or combined deficiency apolipoprotein E (ApoE) tissue inhibitor metalloproteinase-1 (TIMP-1) kept on a cholesterol-rich diet for 30 weeks. Atherosclerotic throughout the thoracic aorta significantly (P<0.001) larger wild-type TIMP-1 (ApoE-/-:TIMP-1+/+) than deficient (ApoE-/-:TIMP-1-/-). Aneurysms abdominal aortas less frequent ApoE-/-:TIMP-1+/+ ApoE-/-:TIMP-1-/- (11+/-3.0 versus 23+/-5.1 aneurysms per 100 sections analyzed, mean+/-SD, P<0.001). Immunocytochemistry revealed enhanced accumulation Oil red O-stained lipids, colocalizing macrophages (P<0.05). In situ zymography using casein substrate showed lysis plaques as compared (P<0.01). MMP activity was most pronounced at sites where degradation elastic lamina occurred. These data suggest that activity, result deficiency, contributes to reduction plaque size but promotes formation.
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