Gelatinases Expression Disturbance as a Possible Cause of Fibromuscular Dysplasia of Internal Carotid Arteries: Immunohistochemical Study

Background: Fibromascular dysplasia of internal carotid arteries (ICA) leading to their pathological deformities is one of the causes of cerebral vascular insufficiency. The structural changes of the artery wall and their causes remain poorly understood. Materials and Methods: We investigated the expression of elastin, collagen types I and III, smooth muscle cells, gelatinases degrading elastin (matrix metalloproteinases 2 and 9 (MMP2 and MMP9) and tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP1 and TIMP2) on formalin-fixed surgical samples with the methods of immunohistochemistry and confocal laser scanning microscopy. Results: We revealed the fragmentation of elastic fibers (100% of patients) and some reduction of smooth muscle cells (p<0.05) in the tunica media of ICA. There were no changes in collagen types I and III and TIMP2 expression. The study of the ratio of the expression of MMPs and TIMPs revealed the statistically significant predominance of high MMP2 and -9 and low TIMP1 content in ICA with pathological deformities. With the use of confocal microscopy, we showed the decrease of elastin expression with a high MMP9 activity which correlated with low expression of TIMP-1 in the group of ICA with pathological deformities. While in the control group there was a high level of elastin expression and a low level of MMP9 expression that correlated with the low TIMP-1 amount (p<0.05). Conclusion: Our data demonstrate that the main feature of fibromuscular dysplasia underlying the pathological deformities of ICA ?fragmentation of elastic fibers ? is caused by the disturbance of balance between gelatinases and their inhibitors