Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms
Matrix metalloproteinases 2 and 9 work in concert to produce aortic aneurysms
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DOI：
10.1172/jci200215334
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发表时间：
2002-09-01
影响因子：
15.9
通讯作者：
Baxter, BT
中科院分区：
文献类型：
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作者：
Longo, GM;Xiong, WF;Baxter, BT
基质金属蛋白酶（MMPs）9和2在人腹主动脉瘤（AAA）组织中增加，但它们的确切作用和潜在的相互作用尚不清楚。在这些肽酶基因缺陷的小鼠中实验诱导主动脉瘤可以为AAA发病机制提供新的见解。MMP-9（MMP-9 KO）或MMP-2（MMP-2KO）表达缺陷的小鼠及其相应的野生型背景小鼠（WT）通过近腔应用氯化钙（CaCl 2）进行AAA诱导。在MMP-9 KO或MMP-2 KO小鼠中，在治疗后10周未观察到动脉瘤形成，而相应的WT小鼠显示主动脉直径分别平均增加74%和52%。将来自相应WT菌株的感受态巨噬细胞再输注到敲除小鼠中导致MMP-9 KO而非MMP-2 KO小鼠中AAA的重建。这些发现表明，巨噬细胞来源的MMP-9和间充质细胞MMP-2都是必需的，并协同工作，以产生AAA。
Matrix metalloproteinases (MMPs) 9 and 2 are increased in human abdominal aortic aneurysm (AAA) tissue, but their precise role and potential interaction remain unclear. Experimental induction of aortic aneurysms in mice genetically deficient in these peptidases could provide new insight into AAA pathogenesis. Mice deficient in the expression of MMP-9 (MMP-9KO) or MMP-2 (MMP-2KO) and their corresponding wild-type background mice (WT) underwent AAA induction by abluminal application of calcium chloride (CaCl2). No aneurysm formation was observed at 10 weeks after treatment in either the MMP-9KO or the MMP-2KO mice, whereas the corresponding WT mice showed an average 74% and 52% increase in aortic diameter, respectively. Reinfusion of competent macrophages from the corresponding WT strains into knockout mice resulted in reconstitution of AAA in MMP-9KO but not MMP-2KO mice. These findings suggest that macrophage-derived MMP-9 and mesenchymal cell MMP-2 are both required and work in concert to produce AAA.