Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms
Matrix metalloproteinase-2 production and its binding to the matrix are increased in abdominal aortic aneurysms
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DOI：
10.1161/01.atv.18.10.1625
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发表时间：
1998-10-01
影响因子：
8.7
通讯作者：
Baxter, BT
中科院分区：
文献类型：
--
作者：
Davis, V;Persidskaia, R;Baxter, BT
弹性介质的降解是腹主动脉瘤（AAA）的标志。我们检测了两种弹性蛋白溶解性基质金属蛋白酶（MMP-2和MMP-9）在AAA主动脉组织中的表达，并与动脉粥样硬化闭塞性疾病（AOD）和正常对照组织进行比较。定量竞争性逆转录-聚合酶链反应和明胶酶谱显示MMP-9 mRNA和蛋白在AAA和AOD组织中均较对照组增加，但在AAA和AOD组织中差异无统计学意义。与此相反，MMP-2的mRNA和蛋白水平显着高于AAA比在AOD或对照组织。用生理盐水、2%二甲基亚砜（DMSO）和10 mol/L尿素从主动脉组织中连续提取MMP，结果显示大量MMP-2和MMP-9与基质结合。最明显的发现是，MMP-2的水平显着升高，在AAA组织中的DMSO部分相比，AOD和对照组织。此外，在DMSO和尿素组分中发现的大部分MMP-2是活性62-kDa形式，表明AAA中MMP-2的前体在很大程度上局部活化并与组织基质紧密结合。通过免疫定位，发现MMP-9主要由巨噬细胞产生，MMP-2由间充质细胞产生。MMP-2的产生是突出的间充质细胞周围的炎性细胞，表明旁分泌调节MMP-2的表达在AAAs。这些观察结果强调，MMP-2通过降解主动脉组织基质成分参与AAA的进展。
Degradation of the elastic media is a hallmark of abdominal aortic aneurysms (AAAs). We examined the expression of 2 elastolytic matrix metalloproteinases (MMPs), MMP-2 and MMP-9, in AAA aortic tissues compared with those from atherosclerotic occlusive disease (AOD) and nondiseased control tissues. Quantitative competitive reverse transcription-polymerase chain reaction and gelatin zymography showed increased MMP-9 mRNA and protein in both AAA and AOD tissues compared with those in control tissue, but there was no significant difference between AAA and AOD. In contrast, MMP-2 mRNA and protein levels were significantly higher in AAA than in AOD or control tissues. Sequential extraction of the MMPs from the aortic tissue with a physiological salt solution, 2% dimethylsulfoxide (DMSO), and 10 mol/L urea showed that large amounts of MMP-2 and MMP-9 were bound to the matrix. The most conspicuous finding was that the levels of MMP-2 were significantly elevated in the DMSO fraction in AAA tissues compared with AOD and control tissues. In addition, a large portion of MMP-2 found in the DMSO and urea fractions was in the active 62-kDa form, indicating that the precursor of MMP-2 in AAA is largely activated locally and binds to the tissue matrix tightly. By immunolocalization, MMP-9 was found to be primarily produced by macrophages and MMP-2 by mesenchymal cells. The production of MMP-2 was prominent when mesenchymal cells were surrounded by inflammatory cells, suggesting paracrine modulation of MMP-2 expression in AAAs. These observations emphasize that MMP-2 participates in the progression of AAAs by degrading aortic tissue matrix components.