Collagen and elastin degradation by matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase in aortic dissection
Collagen and elastin degradation by matrix metalloproteinases and tissue inhibitors of matrix metalloproteinase in aortic dissection
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DOI：
10.1053/hupa.2000.7642
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发表时间：
2000-06-01
期刊：
影响因子：
3.3
通讯作者：
Asuwa, N
中科院分区：
文献类型：
--
作者：
Ishii, T;Asuwa, N
对21例急性主动脉夹层（AD）胶原纤维和弹性纤维的降解进行了超微结构和免疫组化观察，并对分解代谢的基质金属蛋白酶（MMPs）-1、-2、-3、-9及其抑制剂基质金属蛋白酶组织抑制剂（TIMPs）-1、-2的表达进行了研究。将夹层（ES; 21例升结肠）入口部位的特征与完全远端部位（RS; 19例未夹层的腹主动脉瘤）和10例对照病例的升结肠进行比较。通过电子显微镜，在ES和相邻的完整的主动脉壁的中层表现出明显增厚的胶原纤维，具有典型的带状图案，几乎总是与弹性层共定位，这往往表现出衰减，碎片，或中断。此外，在ES时，包围构成中膜的平滑肌细胞（SMC）的基底膜经常变薄或丢失。这些发现很少见于RS或对照组的直肠。免疫组化结果显示，与对照组和RS组相比，MMP-1在ES组和邻近的完整壁的内膜和中膜SMC的胞浆中表达显著，MMP-2和MMP-9在内膜SMC中表达显著。TIMP-1和TIMP-2在ES和邻近完整壁的SMC胞浆中的表达与RS和对照标本相比显著增加。这些研究结果表明，与纤维化和AD的发生相关的蛋白质的降解不仅是一致的，而是AD是由细胞外基质的改变引起的，所述细胞外基质的改变是由通过血流动力学应激，特别是由高血压引起的升主动脉的一段平滑肌细胞的变化引起的。《人文哲学》31：640-646。Copyright（C）2000 by W.B.桑德斯公司
The degradation of collagen fibrils and elastic fibers in 21 cases of acute aortic dissection (AD) was ultrastructurally and immunohistochemically investigated; and the expression of the catabolic matrix metalloproteinases (MMPs)-1, -2, -3, and -9 and their inhibitors, the tissue inhibitors of matrix metalloproteinase (TIMPs)-1 and -2, was studied. The features of the entry site of the dissection (ES; 21 ascending aortas) were compared with those of fully remote sites (RS; 19 nondissected abdominal aortas) and the ascending aortas from 10 control cases. By electron microscopy, the medial layer at the ES and adjacent intact aortic wall demonstrated spirally thickened collagen fibrils with a typical banding pattern that were almost always colocalized with elastic lamellae, which often exhibited attenuation, fragmentation, or disruption. In addition, the basement membrane surrounding the smooth muscle cells (SMCs) comprising the media was frequently thinned or lost at the ES. These findings were rarely seen at the RS or in the aortas of controls. Immunohistochemically, the expression of MMP-1 was significantly in the cytoplasm of SMCs of both the intima and media at the ES and adjacent intact wall, and significant expression of MMP-2 and -9 was found in SMCs of the intima compared with the RS and controls. Significant expression of TIMP-1 and -2 was demonstrated in the cytoplasm of SMCs at the ES and adjacent intact wall compared with that at the RS and the control specimens. These findings suggest that the degradation of proteins associated with fibrosis and the occurrence of AD are not merely coincident, but rather that AD is induced by alterations of the extracellular matrix caused by changes of SMCs at a segment of the ascending aorta made vulnerable through hemodynamic stress, especially that caused by hypertension. HUM PATHOL 31:640-646. Copyright (C) 2000 by W.B. Saunders Company.