Matrix metalloproteinases are involved in a complex multifactorial process of atherosclerotic plaque formation and play a leading role in the degradation of the extracellular matrix components and increase the migratory activity of cellular elements of the vascular wall. Despite a number of scientific studies, it is necessary to identify clear biochemical markers for the development of atherosclerotic lesions. The purpose of the study was to investigate the relationship between the activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 in myocardial homogenate with changes of the cells composition in the coronary arteries wall in experimental atherosclerosis. Materials and methods. The studies were performed on 76 nonlinear rats, which were divided into 3 groups: group Ia was the control (n=20) – animals, injected intracutaneously with 0.1 ml of 0.9 % sodium chloride solution; Ib – comparison group (n=20) – animals injected with incomplete Freund’s adjuvant at the dose of 0.1 ml intracutaneously and II – experimental group (n=36), which were immunized with native human low-density lipoprotein at a single dose of 200 μg, diluted in 0.1 ml of incomplete Freund’s adjuvant, regardless of the weight. The experiment lasted for 20 weeks. Material sampling was performed, starting from the 4th week after the drug administration. From the coronary arteries and the adjacent myocardium, microslides were made according to the generally accepted technique, which were stained with hematoxylin and eosin, according to the methods of Van Gizon, Mallory and Sudan III. The activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 was determined by enzyme-zimografic method. Results and discussion. The growth of matrix metalloproteinase-2 and matrix metalloproteinase-9 activity in atherosclerotic lesions showed stages of degradation of extracellular matrix components: the dynamics of matrix metalloproteinase-2 activity during the experiment increased from 109.1±1.23 % at the 12th week to 127.32±0.99 % at the 20th week. The increased activity of matrix metalloproteinase-2 was associated with an increase in the number of leukocytes and macrophages, including foam cells. The activity of matrix metalloproteinase-9 reached the highest values of 98.24±0.82% at the 8th period from the onset of changes to the final level of 86.26±0.54% at the maximum terms of the experiment. Conclusion. The growing activity of matrix metalloproteinase-9 indicated the development of early atherosclerotic lesions, while the high level of activity of matrix metalloproteinase-2 indicated significant structural changes in the wall of the coronary arteries

Keywords: atherosclerosis, coronary arteries, matrix metalloproteinases, rats

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1. Rahman MS, Woollard K. Atherosclerosis. Adv Exp Med Biol. 2017; 1003: 121-44. https://doi.org/10.1007/978-3-319- 57613-8_7
2. Pende A, Artom N, Bertolotto M, Montecucco F, Dallegri F. Role of neutrophils in atherogenesis: an update. European Journal of Clinical Investigation. 2016 Feb 2; 46(3): 252–63. https://doi.org/10.1111/eci.12566
3. Bobryshev YV, Nikiforov NG, Elizova NV, Orekhov AN. Macrophages and their contribution to the development of atherosclerosis. Results Probl Cell Differ. 2017; 62: 273-98. https://doi.org/10.1007/978-3-319-54090-0_11
4. Ruddy JM, Ikonomidis JS, Jones JA. Multidimensional contribution of matrix metalloproteinases to atherosclerotic plaque vulnerability: multiple mechanisms of inhibition to promote stability. J Vasc Res. 2016; 53: 1-16. https://doi.org/10.1159/000446703
5. Sapa-Wojciechowska А, Rak-Pasikowska А, Pormańczuk К, Czapla В. Extracellular Matrix Remodeling Factors as Markers of Carotid Artery Atherosclerosis. Cardiology Research and Practice. 2020 Aug 12; Article ID 9036157, 11 pages. https://doi.org/10.1155/2020/9036157
6. Markelova EV, Zdor VV, Romanchuk AL, Birko ON. Matriksnye metalloproteinazi i ih vzaimosvjaz' s sistemoj citokinov, diagnosticheskij i prognosticheskij potencial [Matrix metalloproteinases and their relationship with the cytokine system, diagnostic and prognostic potential]. Immunopatologija, Allergologija, Infektologija. 2016; 2: 11-22. [Russian]
7. Wagsater D, Zhu C, Bjorkegren J, Skogsberg J, Eriksson P. MMP-2 and MMP-9 are prominent matrix metalloproteinases during atherosclerosis development in the Ldlr(-/-) Apob (100/100) mouse. Int J Mol Med. 2011 Aug; 28(2): 247-53. https://doi.org/10.3892/ijmm.2011.693
8. Park J, Choi H, Abekura F, Lim HS, Im JH. Avenanthramide C Suppresses Matrix Metalloproteinase-9 Expression and Migration Through the MAPK/NF- κB Signaling Pathway in TNF-α-Activated HASMC Cells. Front Pharmacol. 2021 Mar 25; 12: 621854. https://doi.org/10.3389/fphar.2021.621854
9. Sabry M, Mostafa S, Rashed L, Abdelgwad M, Kamar S, Estaphan S. Matrix metalloproteinase 9 a potential major player connecting atherosclerosis and osteoporosis in high fat diet fed rats. PLoS One. 2021 Feb 11; 16(2): e0244650. https://doi.org/10.1371/journal.pone.0244650
10. Galis ZS, Johnson C, Godin D, Magid R, Shipley JM, Senior RM, et al. Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling. Circular Reseach. 2002 Nov 1; 91(9): 852-9.
11. Shlyakhto EV, Gavrysheva NA, Ovchynnykova OA, Khansson GK. Vlyyanye yndutsyrovannogo vospalenyya na metabolyzm kollagena v aterosklerotycheskykh blyashkakh u myshey [Effect of induced inflammation on collagen metabolism in atherosclerotic plaques in mice]. Medytsynskaya ymmunologyya. 2008; 10(6): 507-12. [Russian]. https://doi.org/10.15789/1563-0625-2008-6-507-512
12. Men'shykov YV, Fomyna KV, Beduleva LV. Eksperymental'naja model' ateroskleroza u krys, vyzvannogo ymmunyzacyej natyvnymy lypoproteynamy cheloveka [Experimental model of atherosclerosis in rats caused by immunization with native human lipoproteins]. Vestnyk Udmurdskogo unyversyteta. 2012; 1: 80-6. [Russian]
13. Patent 83196 Ukraine, MPK G01N 33/49, G01N 27/26, G01N 33/84, G01N 33/96. Sposib viznachennya zhelatinaz u plazmi krovi [Method for determination of gelatinazes in blood plasma] / Shevtsova AI, Gordienko YuA, Shaulska OE, Skoromna AS. (UA); zayavnik i vlasnik patentu Derzhavnyy Zaklad "Dnipropetrovska Medychna Akademiya Ministerstva Okhorony Zdorov'ya Ukrayiny" (UA). № u 2013 03700; zayavl 26.03.2013 ; opubl 27.08.2013. Byul № 16. [Ukrainian]
14. Shponka IS, Svyatenko TV, Voznyak IYa, Poslavska O.V. Analiz pokaznykiv ekspresiyi imunogistokhimichnykh markeriv proliferatsiyi, vaskulyaryzatsiyi, apoptozu, CD3+ i CD68+ mononuklearnoyi infiltratsiyi ta klityn Langergansa v zalezhnosti vid formy ta vazhkosti perebigu psoriazu [Analysis of expression indicators of immunohistochemical markers of proliferation, vascularization, apoptosis, CD3 + and CD68 + mononuclear infiltration and Langengars cells in the shape of the form and severity of psoriasis]. Morfologiya. 2013; 7(3): 117-26. [Ukrainian]