Collagen and Elastin Degradation by Matrix Metalloproteinases and Tissue Inhibitors of Matrix Metalloproteinases in Acute Aortic Dissection and Atherosclllerotic Aneurysm.

应用基质金属蛋白酶S(MMPs)-1、2、3和9及其组织抑制物(TIMPS)-1和2对急性主动脉夹层中胶原和弹性蛋白的降解过程进行了超微结构和免疫组织化学研究。将年龄、性别匹配的对照组的夹层进入点(ES)的结果与与ES及升主动脉完全远离的点(RS)的结果进行比较。电子显微镜下可见螺旋增厚的胶原蛋白与正常的胶原蛋白、弹性蛋白同时出现，呈螺旋状增厚，常呈条带状或断裂。此外，在这种情况下，包括介质的平滑肌细胞(SMC)细胞质周围的基底膜经常变薄或丢失。这些结果仅见于AAD患者RS的主动脉壁，不仅在动脉内膜和中膜的SMC胞浆中有明显的表达，而且在瘤内的表达也明显高于AAD患者的RS和对照组的升主动脉。TIMP-1和TIMP-2在AAD患者的ES显著表达，与AAD患者的RS和对照组升主动脉相比，差异有统计学意义。这些结果表明，胶原和弹性蛋白的降解和AAD的发生并不是偶然发生的，而AAD是由升主动脉易损段的SMC通过血流动力学应激改变而引起的细胞外基质的先前改变而引起的，这是高血压进一步介导的结果。

Degradation process of collagen and elastin in acute aortic dissection (AAD) has been ultra-structurally and immunohistochemically investigated with matrix metalloproteinase s(MMPs)-1, 2, 3 amd-9, and their counterparts of tissue inhibitors of matrix metalloproteinases (TIMPs)-1 and -2. The results at entry site(ES) of dissection were compared with those at fully remote site from ES(RS) and ascending aortas from age-sex matched control cases. By electron microscopy on disscted media, spirally thickened collagen with usual banding pattern were con-currently noted together with normal collagen and elastin often exhibiting fragmentation or disruption. In addition, basement membrane surrounding cytoplasm of smooth muscle cells(SMCs) comprising media was frequently thinned or lost at such circumstances. These findings were only rarely shown in the aortic walls at RS in AAD cases, not only the expression of MMP-1 was significantly distinct in SMC cytoplasm of both intima and media, but also significant expression of MMP-2 and -9 was recognized in intoma, when compared with those expressions at RS in AAD cases and at ascending aortas of controls. Significant expression of TIMP-1 and -2 was correspondingly demonstrated at ES in AAD cases, when compared with that at RS in AAD cases and at ascending aorta of controls. These findings suggest that both degradation of collagen and elastin and occurrence of AAD do not incidentally take place, rather AAD is induced by the preceding alterations of those extracellular matrices caused by alterations of SMCs at vulnerable segment of ascending aorta through hemodynamic stress, which is further mediated by hypertension.