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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">vtio</journal-id><journal-title-group><journal-title xml:lang="ru">Вестник трансплантологии и искусственных органов</journal-title><trans-title-group xml:lang="en"><trans-title>Russian Journal of Transplantology and Artificial Organs</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1995-1191</issn><publisher><publisher-name>Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15825/1995-1191-2021-3-115-121</article-id><article-id custom-type="elpub" pub-id-type="custom">vtio-1217</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>РЕГЕНЕРАТИВНАЯ МЕДИЦИНА И КЛЕТОЧНЫЕ ТЕХНОЛОГИИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REGENERATIVE MEDICINE  AND CELL TECHNOLOGIES</subject></subj-group></article-categories><title-group><article-title>Экспрессия тканевых ингибиторов металлопротеиназ типа 1 и 2 в створках эксплантированных биопротезов клапанов сердца – новая патогенетическая параллель между структурной дегенерацией клапана и кальцинирующим аортальным стенозом</article-title><trans-title-group xml:lang="en"><trans-title>Expression of tissue inhibitors of metalloproteinases type 1 and type 2 in the leaflets of explanted bioprosthetic heart valves: a new pathogenetic parallel between structural valve degeneration and calcific aortic stenosis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Костюнин</surname><given-names>А. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Kostyunin</surname><given-names>A. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Костюнин Александр Евгеньевич, научный сотрудник Лаборатории новых биоматериалов</p><p>650002, Кемерово, Сосновый бульвар, 6</p></bio><bio xml:lang="en"><p>Alexander E. Kostyunin, Researcher, Laboratory of New Biomaterials</p><p>6, Sosnovy Boulevard, Kemerovo, 650002</p></bio><email xlink:type="simple">Rhabdophis_tigrina@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Глушкова</surname><given-names>Т. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Glushkova</surname><given-names>T. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кемерово</p></bio><bio xml:lang="en"><p>Kemerovo</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Богданов</surname><given-names>Л. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Bogdanov</surname><given-names>L. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кемерово</p></bio><bio xml:lang="en"><p>Kemerovo</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Овчаренко</surname><given-names>Е. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Ovcharenko</surname><given-names>E. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кемерово</p></bio><bio xml:lang="en"><p>Kemerovo</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Research Institute for Complex Issues of Cardiovascular Diseases</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>17</day><month>09</month><year>2021</year></pub-date><volume>23</volume><issue>3</issue><fpage>115</fpage><lpage>121</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Костюнин А.Е., Глушкова Т.В., Богданов Л.А., Овчаренко Е.А., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Костюнин А.Е., Глушкова Т.В., Богданов Л.А., Овчаренко Е.А.</copyright-holder><copyright-holder xml:lang="en">Kostyunin A.E., Glushkova T.V., Bogdanov L.A., Ovcharenko E.A.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://journal.transpl.ru/vtio/article/view/1217">https://journal.transpl.ru/vtio/article/view/1217</self-uri><abstract><sec><title>Цель</title><p>Цель: изучить клеточную и липидную инфильтрацию, а также экспрессию тканевых ингибиторов металлопротеиназ (ТИМП) типа 1 и 2 в створках биологических протезов клапанов сердца (БПК), эксплантированных по причине дисфункций.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. Исследовано 17 створок от 6 БПК, иссеченных из аортальной и митральной позиций при репротезировании клапанов. Для выполнения микроскопического анализа фрагменты створок БПК замораживали и с помощью криотома изготавливали серийные срезы. С целью изучения клеточной инфильтрации и степени дегенеративных изменений протезного биоматериала срезы окрашивали гематоксилином Джилла и эозином, для оценки отложения липидов использовали окраску Oil Red. С целью типирования клеток и выявления ТИМП-1/-2 применяли иммуногистохимический метод. Анализ окрашенных образцов осуществляли методом световой микроскопии.</p></sec><sec><title>Результаты</title><p>Результаты. Клеточная и липидная инфильтрация ксенотканей выявлена во всех исследованных створках БПК. Клетки реципиентов коэкспрессировали панлейкоцитарный и макрофагальный маркеры PTPRC/CD45 и CD68. Положительная окраска на ТИМП-1/-2 солокализовалась с клеточными скоплениями, но отсутствовала в бесклеточных участках.</p></sec><sec><title>Заключение</title><p>Заключение. Клетки, проникающие в ксеногенные ткани БПК, экспрессируют ТИМП-1/-2. Это указывает на частичное сходство патофизиологии иммунного отторжения БПК с таковой кальцинирующего аортального стеноза.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Objective</title><p>Objective: to study cellular and lipid infiltration, as well as the expression of tissue inhibitors of metalloproteinases (TIMP) types 1 and 2 in biological prosthetic heart valves (BPHVs) explanted due to dysfunction.</p></sec><sec><title>Material and Methods</title><p>Material and Methods. We examined 17 leaflets from 6 BPHVs, dissected from the aortic and mitral positions during valve replacement. For microscopic analysis, fragments of the BPHV leaflets were frozen and serial sections were made using a cryotome. In order to study cellular infiltration and the degree of degenerative changes in the prosthetic biomaterial, the sections were stained with Gill’s hematoxylin and eosin; Oil Red O stain was used to assess lipid deposition. Immunohistochemistry was used for cell typing and detection of TIMP-1/-2. The stained samples were analyzed by light microscopy.</p></sec><sec><title>Results</title><p>Results. Cellular and lipid infiltration of xenogeneic tissues was detected in all BPHV flaps studied. Recipient cells coexpressed pan-leukocyte and macrophage markers PTPRC/CD45 and CD68. Positive staining for TIMP-1/-2 co-localized with cell clusters but was absent in acellular sections.</p></sec><sec><title>Conclusion</title><p>Conclusion. Cells infiltrating xenogeneic BPHV tissues express TIMP-1/-2. This suggests that BPHV immune rejection pathophysiology is partially similar to that of calcific aortic stenosis.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>биопротезы клапанов сердца</kwd><kwd>структурная дегенерация клапана</kwd><kwd>кальцинирующий аортальный стеноз</kwd><kwd>клеточная инфильтрация</kwd><kwd>липиды</kwd><kwd>тканевые ингибиторы металлопротеиназ</kwd></kwd-group><kwd-group xml:lang="en"><kwd>bioprosthetic heart valves</kwd><kwd>structural valve degeneration</kwd><kwd>calcific aortic stenosis</kwd><kwd>cellular infiltration</kwd><kwd>lipids</kwd><kwd>tissue inhibitors of metalloproteinases</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Pibarot P, Dumesnil JG. Prosthetic heart valves: selection of the optimal prosthesis and long-term management. Circulation. 2009; 119 (7): 1034–1048. doi: 10.1161/CIRCULATIONAHA.108.778886.</mixed-citation><mixed-citation xml:lang="en">Pibarot P, Dumesnil JG. Prosthetic heart valves: selection of the optimal prosthesis and long-term management. Circulation. 2009; 119 (7): 1034–1048. doi: 10.1161/CIRCULATIONAHA.108.778886.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Овчаренко ЕА, Клышников КЮ, Глушкова ТВ, Нуштаев ДВ, Кудрявцева ЮА, Саврасов ГВ. Выбор ксеноперикардиального лоскута для створчатого аппарата транскатетерных биопротезов клапанов сердца. Медицинская техника. 2015; 5: 1–4.</mixed-citation><mixed-citation xml:lang="en">Ovcharenko EA, Klyshnikov KYu, Glushkova TV, Nushtaev DV, Kudryavtseva YuA, Savrasov GV. The choosing of the xenopericardial patch for transcatheter heart valve. Medical equipment. 2015; 5: 1–4. [In Russ].</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Capodanno D, Petronio AS, Prendergast B, Eltchaninoff H, Vahanian A, Modine T et al. Standardized definitions of structural deterioration and valve failure in assessing long-term durability of transcatheter and surgical aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) endorsed by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2017; 38 (45): 3382–3390. doi: 10.1093/eurheartj/ehx303.</mixed-citation><mixed-citation xml:lang="en">Capodanno D, Petronio AS, Prendergast B, Eltchaninoff H, Vahanian A, Modine T et al. Standardized definitions of structural deterioration and valve failure in assessing long-term durability of transcatheter and surgical aortic bioprosthetic valves: a consensus statement from the European Association of Percutaneous Cardiovascular Interventions (EAPCI) endorsed by the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2017; 38 (45): 3382–3390. doi: 10.1093/eurheartj/ehx303.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Dvir D, Bourguignon T, Otto CM, Hahn RT, Rosenhek R, Webb JG et al. Standardized definition of structural valve degeneration for surgical and transcatheter bioprosthetic aortic valves. Circulation. 2018; 137 (4): 388–399. doi: 10.1161/CIRCULATIONAHA.117.030729.</mixed-citation><mixed-citation xml:lang="en">Dvir D, Bourguignon T, Otto CM, Hahn RT, Rosenhek R, Webb JG et al. Standardized definition of structural valve degeneration for surgical and transcatheter bioprosthetic aortic valves. Circulation. 2018; 137 (4): 388–399. doi: 10.1161/CIRCULATIONAHA.117.030729.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Lindman BR, Clavel MA, Mathieu P, Iung B, Lancellotti P, Otto CM et al. Calcific aortic stenosis. Nat Rev Dis Primers. 2016; 2: 16006. doi: 10.1038/nrdp.2016.6.</mixed-citation><mixed-citation xml:lang="en">Lindman BR, Clavel MA, Mathieu P, Iung B, Lancellotti P, Otto CM et al. Calcific aortic stenosis. Nat Rev Dis Primers. 2016; 2: 16006. doi: 10.1038/nrdp.2016.6.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Shetty R, Pibarot P, Audet A, Janvier R, Dagenais F, Perron J et al. Lipid-mediated inflammation and degeneration of bioprosthetic heart valves. Eur J Clin Invest. 2009; 39 (6): 471–480. doi: 10.1111/j.1365-2362.2009.02132.x.</mixed-citation><mixed-citation xml:lang="en">Shetty R, Pibarot P, Audet A, Janvier R, Dagenais F, Perron J et al. Lipid-mediated inflammation and degeneration of bioprosthetic heart valves. Eur J Clin Invest. 2009; 39 (6): 471–480. doi: 10.1111/j.1365-2362.2009.02132.x.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Simionescu A, Simionescu DT, Deac RF. Matrix metalloproteinases in the pathology of natural and bioprosthetic cardiac valves. Cardiovasc Pathol. 1996; 5 (6): 323–332. PMID: 25851789.</mixed-citation><mixed-citation xml:lang="en">Simionescu A, Simionescu DT, Deac RF. Matrix metalloproteinases in the pathology of natural and bioprosthetic cardiac valves. Cardiovasc Pathol. 1996; 5 (6): 323–332. PMID: 25851789.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Cote N, Pibarot P, Clavel MA. Incidence, risk factors, clinical impact, and management of bioprosthesis structural valve degeneration. Curr Opin Cardiol. 2017; 32 (2): 123–129. doi: 10.1097/HCO.0000000000000372.</mixed-citation><mixed-citation xml:lang="en">Cote N, Pibarot P, Clavel MA. Incidence, risk factors, clinical impact, and management of bioprosthesis structural valve degeneration. Curr Opin Cardiol. 2017; 32 (2): 123–129. doi: 10.1097/HCO.0000000000000372.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Bosse Y, Miqdad A, Fournier D, Pepin A, Pibarot P, Mathieu P. Refining molecular pathways leading to calcific aortic valve stenosis by studying gene expression profile of normal and calcified stenotic human aortic valves. Circ Cardiovasc Genet. 2009; 2 (5): 489–498. doi: 10.1161/CIRCGENETICS.108.820795.</mixed-citation><mixed-citation xml:lang="en">Bosse Y, Miqdad A, Fournier D, Pepin A, Pibarot P, Mathieu P. Refining molecular pathways leading to calcific aortic valve stenosis by studying gene expression profile of normal and calcified stenotic human aortic valves. Circ Cardiovasc Genet. 2009; 2 (5): 489–498. doi: 10.1161/CIRCGENETICS.108.820795.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Fondard O, Detaint D, Iung B, Choqueux C, Adle-Biassette H, Jarraya M et al. Extracellular matrix remodelling in human aortic valve disease: the role of matrix metalloproteinases and their tissue inhibitors. Eur Heart J. 2005; 26 (13): 1333–1341. doi: 10.1093/eurheartj/ehi248.</mixed-citation><mixed-citation xml:lang="en">Fondard O, Detaint D, Iung B, Choqueux C, Adle-Biassette H, Jarraya M et al. Extracellular matrix remodelling in human aortic valve disease: the role of matrix metalloproteinases and their tissue inhibitors. Eur Heart J. 2005; 26 (13): 1333–1341. doi: 10.1093/eurheartj/ehi248.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Arpino V, Brock M, Gill SE. The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix Biol. 2015; 44–46: 247–254. doi: 10.1016/j.matbio.2015.03.005.</mixed-citation><mixed-citation xml:lang="en">Arpino V, Brock M, Gill SE. The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix Biol. 2015; 44–46: 247–254. doi: 10.1016/j.matbio.2015.03.005.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Ries C. Cytokine functions of TIMP-1. Cell Mol Life Sci. 2014; 71 (4): 659–672. doi: 10.1007/s00018-013-1457-3.</mixed-citation><mixed-citation xml:lang="en">Ries C. Cytokine functions of TIMP-1. Cell Mol Life Sci. 2014; 71 (4): 659–672. doi: 10.1007/s00018-013-1457-3.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Богданов ЛА, Кутихин АГ. Оптимизация окрашивания элементов системы кровообращения и гепатолиенальной системы гематоксилином и эозином. Фундаментальная и клиническая медицина. 2019; 4 (4): 70–77. doi: 10.23946/2500-0764-2019-4-4-70-77.</mixed-citation><mixed-citation xml:lang="en">Bogdanov LA, Kutikhin AG. Optimization of hematoxylin and eosin staining of heart, blood vessels, liver, and spleen. Fundamental and Clinical Medicine. 2019; 4 (4): 70–77. [in Russian]. doi: 10.23946/2500-0764-2019-4-4-70-77.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Костюнин АЕ, Глушкова ТВ. Первые результаты изучения экспрессии матриксных металлопротеиназ-1/-2/-9/-12 в ксеногенных тканях эпоксиобработанных биопротезов клапанов сердца, эксплантированных по причине дисфункций. Российский кардиологический журнал. 2020; 25 (10): 49–55. doi: 10.15829/1560-4071-2020-3978.</mixed-citation><mixed-citation xml:lang="en">Kostyunin AE, Glushkova TV. The first results of the study of matrix metalloproteinases-1/-2/-9/-12 expression in xenogenic tissues of epoxy-treated bioprosthetic heart valves explanted due to dysfunctions. Russian Journal of Cardiology. 2020; 25 (10): 49–55. doi: 10.15829/1560-4071-2020-3978.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Kostyunin A, Mukhamadiyarov R, Glushkova T, Bogdanov L, Shishkova D, Osyaev N et al. Ultrastructural pathology of atherosclerosis, calcific aortic valve disease, and bioprosthetic heart valve degeneration: commonalities and differences. Int J Mol Sci. 2020; 21 (20): E7434. doi: 10.3390/ijms21207434.</mixed-citation><mixed-citation xml:lang="en">Kostyunin A, Mukhamadiyarov R, Glushkova T, Bogdanov L, Shishkova D, Osyaev N et al. Ultrastructural pathology of atherosclerosis, calcific aortic valve disease, and bioprosthetic heart valve degeneration: commonalities and differences. Int J Mol Sci. 2020; 21 (20): E7434. doi: 10.3390/ijms21207434.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Lee S, Levy RJ, Christian AJ, Hazen SL, Frick NE, Lai EK et al. Calcification and oxidative modifications are associated with progressive bioprosthetic heart valve dysfunction. J Am Heart Assoc. 2017; 6 (5). pii: e005648. doi: 10.1161/JAHA.117.005648.</mixed-citation><mixed-citation xml:lang="en">Lee S, Levy RJ, Christian AJ, Hazen SL, Frick NE, Lai EK et al. Calcification and oxidative modifications are associated with progressive bioprosthetic heart valve dysfunction. J Am Heart Assoc. 2017; 6 (5). pii: e005648. doi: 10.1161/JAHA.117.005648.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Di Gregoli K, George SJ, Jackson CL, Newby AC, Johnson JL. Differential effects of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 on atherosclerosis and monocyte/macrophage invasion. Cardiovasc Res. 2016; 109 (2): 318–330. doi: 10.1093/cvr/cvv268.</mixed-citation><mixed-citation xml:lang="en">Di Gregoli K, George SJ, Jackson CL, Newby AC, Johnson JL. Differential effects of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 on atherosclerosis and monocyte/macrophage invasion. Cardiovasc Res. 2016; 109 (2): 318–330. doi: 10.1093/cvr/cvv268.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
