Gelatinases Expression Disturbance as a Possible Cause of Fibromuscular Dysplasia of Internal Carotid Arteries: Immunohistochemical Study
International Journal of Clinical and Experimental Medical Sciences
Volume 2, Issue 4, July 2016, Pages: 52-58
Received: Mar. 16, 2016;
Accepted: May 17, 2016;
Published: Jul. 5, 2016
Views 3592 Downloads 76
Ekaterina M. Paltseva, B. V. Petrovsky Russian Research Center of Surgery, Moscow, Russia
Viktoria O. Polyakova, D. O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia
Svetlana A. Oskolkova, I. M. Sechenov First Moscow State Medical University, Moscow, Russia
Arsen V. Abramyan, B. V. Petrovsky Russian Research Center of Surgery, Moscow, Russia
Julia S. Krylova, D. O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia
Alexandre V. Gavrilenko, B. V. Petrovsky Russian Research Center of Surgery, Moscow, Russia
Igor M. Kvetnoy, D. O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia
Follow on us
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.
Pathological Deformities of Internal Carotid Artery, Elastin, Collagen, Smooth Muscle Cells, Matrix Metalloproteinase, Tissue Inhibitor of Matrix Metalloproteinases
To cite this article
Ekaterina M. Paltseva,
Viktoria O. Polyakova,
Svetlana A. Oskolkova,
Arsen V. Abramyan,
Julia S. Krylova,
Alexandre V. Gavrilenko,
Igor M. Kvetnoy,
Gelatinases Expression Disturbance as a Possible Cause of Fibromuscular Dysplasia of Internal Carotid Arteries: Immunohistochemical Study, International Journal of Clinical and Experimental Medical Sciences.
Vol. 2, No. 4,
2016, pp. 52-58.
Copyright © 2016 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/
) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Horev NG, Pathological tortuosity of internal carotid artery and its surgical treatment. Dissertation, Barnaul; 2000.
Bokeria LA, Sukhanov SG, Katkov AI, Pirtskhalaishvili ZK Surgery of pathological tortuosity of brachiocephalic arteries. Perm: Kursiv; 2006.
Illuminati G, Caliо FG, Papaspyropoulos V, Montesano G, D'Urso A Revascularization of the internal carotid artery for isolated, stenotic, and symptomatic kinking. Arch Surg. 2003; 138(2): 192-197.
Nikonenko AS, Gubka AV, Masterukhin AN, Gubka VA Estimation of the cerebral hemodynamics in patients with pathological kinking of arteries originated from the aortal arch according to angiography. Klin Khir. 2000; 10:5-7.
Smirnova YuV, Al'myasheva LI Etiology of pathological deformation of internal carotid arteries and pathogenesis of cerebral circulation disturbances in this anomaly (review). Klinicheskaya Nevrologiya. 2012; 1: 33-38.
Khaimovich G Vascular surgery on Khaimovich in 2 volumes. Under edition E. Asher. Moscow: Binom; 2010.
Timina IE, Burtseva EA, Losik IA Modern approach to the complex ultrasound examination of patients with pathological deformation of internal carotid artery. Angiologiya i Sosudistaya Khirurgiya. 2011; 3: 49-57.
Aleksic M, Schütz G, Gerth S, Mulch J Surgical approach to kinking and coiling of the internal carotid artery. J Cardiovasc Surg. 2004; 45(1): 43-48.
Togay-Işikay C, Kim J, Betterman K et al. Carotid artery tortuosity, kinking, coiling: stroke risk factor, marker, or curiosity? Acta Neurol Belg. 2005; 105(2):68-72.
Weibel J, Fields WS Tortuosity, coiling and kinking of the internal carotid artery. I. Etiology and radiographic anatomy. Neurology. 1965; 15: 7-18.
Weibel J, Fields WS Tortuosity, coiling and kinking of the internal carotid artery. II. Relationship of morphological variation to cerebrovascular insufficiency. Neurology. 1965; 15: 462-468.
Mumoli N, Cei M Asymptomatic carotid kinking. Circ J. 2007; 72: 682-683.
Kuzyk YuI Pathological deformations of carotid arteries: etiology, pathogenesis, clinical and pathomorphological changes. Angiologiya i Sosudistaya Khirurgiya. 2014; 20(3): 123-128.
La Barbera G, La Marca G, Martino A et al. Kinking, coiling, and tortuosity of extracranial internal carotid artery: is it the effect of a metaplasia? Sur Radiol Anat. 2006; 28(6): 573-580.
Minkina SM Morphogenesis of fibro-muscular dysplasia of renal arteries. Dissertation, Moscow; 1980.
Ponticos M, Smith B Extracellular matrix synthesis in vascular disease: hypertension, and atherosclerosis. J Biomed Res. 2014; 28(1): 25-39.
Bonderman D, Gharehbaghi-Schnell E, Wollenek G, Maurer G, Baumgartner H, Lang IM Mechanisms underlying aortic dilatation in congenital aortic valve malformation. Circulation. 1999; 99: 2138-2143.
Goodall S, Porter KE, Bell PR, Thompson MM Enhanced invasive properties exhibited by smooth muscle cells are associated with elevated production of MMP-2 in patients with aortic aneurisms. Eur J Vasc Endovasc Surg. 2002; 24(1): 72-80.
Lipp C, Lohoefer F, Reeps C et al. Expression of a disintegrin and metalloprotease in human abdominal aortic aneurysms. J Vasc Res. 2012; 49: 198-206.
Wilson WR, Schwalbe EC, Jones JL, Bell PR, Thompson MM Matrix metalloproteinase 8 (neutrophil collagenase) in the pathogenesis of abdominal aortic aneurism. Br J Surg. 2005; 92(7): 828-833.