Paltseva E M, Polyakova V O, Oskolkova S A, Abramyan A V, Ivanova A G, Krylova Yu S, Gavrilenko A V
Academician B.V. Petrovsky Russian Surgery Research Center, Moscow, Russia.
D.O. Ott Research Institute of Obstetrics, Gynecology, and Reproductology, Saint Petersburg, Russia.
Arkh Patol. 2016 May-Jun;78(3):26-31. doi: 10.17116/patol201678326-31.
The principal morphological sign of fibromuscular dysplasia in pathological tortuosity (PT) of the internal carotid artery (ICA) is the fragmentation of elastic fibers that are degraded by matrix metalloproteinases 2 and 9 (MMP-2, MMP-9). Nevertheless, the role of MMPs and their inhibitors in the pathogenesis of ICA PT remains completely unexplored.
to investigate the expression of elastin-degrading MMPs and their inhibitors in the wall of the ICA in PT by immunohistochemistry and confocal laser scanning microscopy.
Immunohistochemical examination was made using antibodies to MMP-2, MMP-9 and their tissue inhibitors TIMP-1 and TIMP-2. MMP-9 and TIMP-1 levels were determined by confocal laser scanning microscopy.
Immunohistochemical examination revealed a statistically significant predominance of high concentrations of MMP-2 and MMP-9 and a low level of their inhibitor TIMP-1 in ICA PT, while simultaneous obvious accumulation of both markers was most often identified in the control group (p<0.05). Analysis of MMP-2/TIMP-2 and MMP-9/TIMP-2 ratios showed the prevalence of the simultaneously high expression of both proteins in ICA PT and in the control group too. The similar data were also obtained by confocal microscopy: the control group showed elevated MMP-9 and TIMP-1 expressions and the ICA PT control displayed a high proteinase and low inhibitor levels (p<0.05).
Elastic fiber fragmentation in ICA PT is due to imbalance between MMPs and their inhibitors; namely, the prevalence of MMP-2 and MMP-9 over their inhibitor TIMP-1, which leads to the degradation of extracellular matrix components, primarily elastin.
颈内动脉（ICA）病理性迂曲（PT）中纤维肌发育不良的主要形态学标志是弹性纤维的碎片化，这些弹性纤维被基质金属蛋白酶2和9（MMP - 2、MMP - 9）降解。然而，MMPs及其抑制剂在ICA PT发病机制中的作用仍完全未被探索。
通过免疫组织化学和共聚焦激光扫描显微镜研究PT中ICA壁内降解弹性蛋白的MMPs及其抑制剂的表达。
使用针对MMP - 2、MMP - 9及其组织抑制剂TIMP - 1和TIMP - 2的抗体进行免疫组织化学检查。通过共聚焦激光扫描显微镜测定MMP - 9和TIMP - 1水平。
免疫组织化学检查显示，在ICA PT中，高浓度的MMP - 2和MMP - 9占统计学上的显著优势，而其抑制剂TIMP - 1水平较低，而在对照组中最常同时发现两种标志物的明显积累（p<0.05）。MMP - 2/TIMP - 2和MMP - 9/TIMP - 2比值分析表明，在ICA PT和对照组中两种蛋白同时高表达的情况都很普遍。共聚焦显微镜也获得了类似的数据：对照组显示MMP - 9和TIMP - 1表达升高，而ICA PT组显示蛋白酶水平高且抑制剂水平低（p<0.05）。
ICA PT中的弹性纤维碎片化是由于MMPs及其抑制剂之间的失衡；即MMP - 2和MMP - 9相对于其抑制剂TIMP - 1占优势，这导致细胞外基质成分（主要是弹性蛋白）的降解。
