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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">fcmedicine</journal-id><journal-title-group><journal-title xml:lang="ru">Фундаментальная и клиническая медицина</journal-title><trans-title-group xml:lang="en"><trans-title>Fundamental and Clinical Medicine</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2500-0764</issn><issn pub-type="epub">2542-0941</issn><publisher><publisher-name>КемГМУ</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.23946/2500-0764-2022-7-1-17-30</article-id><article-id custom-type="elpub" pub-id-type="custom">fcmedicine-511</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>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL RESEARCH</subject></subj-group></article-categories><title-group><article-title>Молекулярные маркеры фиброза при постинфарктном ремоделировании миокарда</article-title><trans-title-group xml:lang="en"><trans-title>Molecular markers of cardiac fibrosis after myocardial infarction</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4642-3610</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Барбараш</surname><given-names>О. Л.</given-names></name><name name-style="western" xml:lang="en"><surname>Barbarash</surname><given-names>O. L.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Барбараш Ольга Леонидовна, доктор медицинских наук, член-корреспондент РАН, директор</p><p>650002, г. Кемерово, Сосновый бульвар, д. 6</p></bio><bio xml:lang="en"><p>Olga L. Barbarash, MD, DSc, Corresponding Member of theRussian Academy of Sciences, Chief Executive Office</p><p>6, Sosnovy Boulevard, Kemerovo, 650002</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8679-4857</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кутихин</surname><given-names>А. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Kutikhin</surname><given-names>A. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кутихин Антон Геннадьевич, кандидат медицинских наук,заведующий лабораторией молекулярной, трансляционной и цифровой медицины отдела экспериментальной медицины</p><p>650002, г. Кемерово, Сосновый бульвар, д. 6</p></bio><bio xml:lang="en"><p>Anton G. Kutikhin, MD, PhD, Head of the Laboratory for Molecular,Translational and Digital Medicine</p><p>6, Sosnovy Boulevard, Kemerovo, 650002</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4771-484X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Печерина</surname><given-names>Т. Б.</given-names></name><name name-style="western" xml:lang="en"><surname>Pecherina</surname><given-names>T. B.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Печерина Тамара Борзалиевна, кандидат медицинских наук, доцент, старший научный сотрудник лаборатории патологии кровообращения отдела клинической кардиологии</p><p>650002, г. Кемерово, Сосновый бульвар, д. 6</p></bio><bio xml:lang="en"><p>Tamara B. Pecherina, MD, PhD, Senior Research Fellow, Laboratoryfor Circulation Pathology, Department of Clinical Cardiology</p><p>6, Sosnovy Boulevard, Kemerovo, 650002</p></bio><email xlink:type="simple">tb.pechorina@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3882-709X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тарасов</surname><given-names>Р. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Tarasov</surname><given-names>R. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Тарасов Роман Сергеевич, доктор медицинских наук, заведующий лабораторией рентгенэндоваскулярной и реконструктивной хирургии сердца и сосудов отдела хирургии сердца и сосудов</p><p>650002, г. Кемерово, Сосновый бульвар, д. 6</p></bio><bio xml:lang="en"><p>Roman S. Tarasov, MD, DSc, Head of the Laboratory forEndovascular and Reconstructive Surgery, Department of Cardiovascular Surgery</p><p>6, Sosnovy Boulevard, Kemerovo, 650002</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3729-616X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кашталап</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kashtalap</surname><given-names>V. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кашталап Василий Васильевич, доктор медицинских наук, доцент, заведующий отделом клинической кардиологии</p><p>650002, г. Кемерово, Сосновый бульвар, д. 6</p></bio><bio xml:lang="en"><p>Vasiliy V. Kashtalap, MD, DSc, Head of the Department of ClinicalCardiology</p><p>6, Sosnovy Boulevard, Kemerovo, 650002</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3841-8539</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Федорова</surname><given-names>Н. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Fedorova</surname><given-names>N. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Федорова Наталья Васильевна, кандидат медицинских наук, врач-кардиолог, заведующая консультативно-диагностическим отделением</p><p>650002, г. Кемерово, Сосновый бульвар, д. 6</p></bio><bio xml:lang="en"><p>Natalia B. Fedorova, MD, PhD, Head of the Diagnostic Facility </p><p>6, Sosnovy Boulevard, Kemerovo, 650002</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4124-2316</contrib-id><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>Богданов Лев Александрович, младший научный сотрудниклаборатории фундаментальных аспектов атеросклероза отделаэкспериментальной медицины</p><p>650002, г. Кемерово, Сосновый бульвар, д. 6</p></bio><bio xml:lang="en"><p>Leo A. Bogdanov, BSc, Junior Research Fellow, Laboratory forMolecular, Translational and Digital Medicine</p><p>6, Sosnovy Boulevard, Kemerovo, 650002</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6620-5960</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Хрячкова</surname><given-names>О. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Hryachkova</surname><given-names>O. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Хрячкова Оксана Николаевна, кандидат биологических наук,младший научный сотрудник лаборатории геномной медицины отдела экспериментальной медицины</p><p>650002, г. Кемерово, Сосновый бульвар, д. 6</p></bio><bio xml:lang="en"><p>Oksana N. Hryachkova, PhD, Junior Research Fellow, Laboratoryfor Genomic Medicine, Department of Experimental Medicine</p><p>6, Sosnovy Boulevard, Kemerovo, 650002</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7058-2008</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Седых</surname><given-names>Д. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Sedykh</surname><given-names>D. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Седых Дарья Юрьевна, кандидат медицинских наук, научныйсотрудник лаборатории патологии кровообращения отделаклинической кардиологии</p><p>650002, г. Кемерово, Сосновый бульвар, д. 6</p></bio><bio xml:lang="en"><p>Daria Yu. Sedykh, MD, PhD, Research Fellow, Laboratory forCirculation Pathology, Department of Clinical Cardiology</p><p>6, Sosnovy Boulevard, Kemerovo, 650002</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>2022</year></pub-date><pub-date pub-type="epub"><day>30</day><month>03</month><year>2022</year></pub-date><volume>7</volume><issue>1</issue><fpage>17</fpage><lpage>30</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Барбараш О.Л., Кутихин А.Г., Печерина Т.Б., Тарасов Р.С., Кашталап В.В., Федорова Н.В., Богданов Л.А., Хрячкова О.Н., Седых Д.Ю., 2022</copyright-statement><copyright-year>2022</copyright-year><copyright-holder xml:lang="ru">Барбараш О.Л., Кутихин А.Г., Печерина Т.Б., Тарасов Р.С., Кашталап В.В., Федорова Н.В., Богданов Л.А., Хрячкова О.Н., Седых Д.Ю.</copyright-holder><copyright-holder xml:lang="en">Barbarash O.L., Kutikhin A.G., Pecherina T.B., Tarasov R.S., Kashtalap V.V., Fedorova N.V., Bogdanov L.A., Hryachkova O.N., Sedykh D.Y.</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://fcm.kemsmu.ru/jour/article/view/511">https://fcm.kemsmu.ru/jour/article/view/511</self-uri><abstract><p>Несмотря на высокую распространенность и клиническую значимость фиброза миокарда, молекулярно-генетические факторы его реализации в постинфарктном периоде остаются предметом дискуссий.</p><sec><title>Цель</title><p>Цель. Выявление молекулярных маркеров фиброза миокарда при его постинфарктном ремоделировании.</p></sec><sec><title>Материалы и методы</title><p>Материалы и методы. При проведении плановой коронаровентрикулографии выполнялась эндомиокардиальная биопсия миокарда пораженных и интактных областей межжелудочковой перегородки со стороны правого желудочка 7 пациентов с перенесенным передним распространенным инфарктом миокарда. Получены биоптаты фиброзированного и прилежащего здорового миокарда, которые были механически разделены на два равных сегмента и подвергнуты: 1) гомогенизации с последующим выделением РНК, синтезом кД-НК и анализом генной экспрессии при помощи количественной полимеразной цепной реакции; 2) фиксации в формалине и заключению в парафин с дальнейшим окрашиванием по ван Гизону для гистологической верификации фиброза.</p></sec><sec><title>Результаты</title><p>Результаты. Обнаружено, что экспрессия генов ACTA2, VIM, CTGF, COL1A1, TGFB1, TGFBR1, AGTR1, CCL2 и TNF в фиброзированном миокарде более чем в три раза выше, чем в прилежащем здоровом миокарде, что может отражать активный синтез белков экстрацеллюлярного матрикса миофибробластами, дифференцирующимися из синтетически неактивных фибробластов в процессе развития фиброза миокарда, который сопровождается асептическим воспалением.</p></sec><sec><title>Заключение</title><p>Заключение. Впервые показано, что гены AGTR1, CCL2 и TNF могут быть вовлечены в развитие фиброза у пациентов после перенесенного инфаркта миокарда; подтверждена значимость генов ACTA2, VIM, CTGF, COL1A1, TGFB1 и TGFBR1 для этого патологического процесса.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Aim</title><p>Aim. To perform a screening for molecular markers of cardiac fibrosis upon myocardial infarction.</p></sec><sec><title>Materials and Methods</title><p>Materials and Methods. We carried out echocardiography-guided endomyocardial biopsy of affected and intact interventricular septum segments of 7 patients with anterior myocardial infarction. Fibrotic and adjacent intact cardiac tissue was dissected into 2 equal segments and: 1) homogenized with the further RNA extraction, reverse transcription, and quantitative polymerase chain reaction; 2) fixed in formalin and embedded into paraffin with the further van Gieson staining for the histological verification of cardiac fibrosis.</p></sec><sec><title>Results</title><p>Results. We found that the expression of ACTA2, VIM, CTGF, COL1A1, TGFB1, TGFBR1, AGTR1, CCL2 and TNF genes in fibrotic cardiac tissue was ≥ 3-fold higher as compared with the adjacent intact myocardium reflective of active extracellular matrix production by fibroblast-derived myofibroblasts.</p></sec><sec><title>Conclusion</title><p>Conclusion. We have for the first time shown AGTR1, CCL2, and TNF genes as candidates for post-infarction cardiac fibrosis in addition to ACTA2, VIM, CTGF, COL1A1, TGFB1, and TGFBR1 genes.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>инфаркт миокарда</kwd><kwd>фиброз миокарда</kwd><kwd>молекулярные маркеры</kwd><kwd>гены AGTR1</kwd><kwd>CCL2</kwd><kwd>TNF</kwd></kwd-group><kwd-group xml:lang="en"><kwd>myocardial infarction</kwd><kwd>cardiac fibrosis</kwd><kwd>molecular markers</kwd><kwd>AGTR1</kwd><kwd>CCL2</kwd><kwd>TNF</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование выполнено в рамках фундаментальной темы НИР НИИ КПССЗ № 0419-2022-0002 (период выполнения 2022-2026 гг.) «Разработка инновационных моделей управления риском развития болезней системы кровообращения с учетом коморбидности на основе изучения фундаментальных, клинических, эпидемиологических механизмов и организационных технологий медицинской помощи в условиях промышленного региона Сибири» (научный руководитель – член-корреспондент РАН О.Л. Барбараш), № госрегистрации 122012000364-5 от 20.01.2022 г.</funding-statement><funding-statement xml:lang="en">This research was funded by the Complex Program of Basic Research under the Siberian Branch of the Russian Academy of Sciences within the Basic Research Topic of Research Institute for Complex Issues of Cardiovascular Diseases № 0419-2022-0002 «Development of innovative models for management of cardiovascular disease risk factors and comorbid conditions».</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC. Cardiac Fibrosis: The Fibroblast Awakens. Circ Res. 2016;118(6):1021-1040. https://doi.org/10.1161/CIRCRESAHA.115.306565</mixed-citation><mixed-citation xml:lang="en">Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC. Cardiac Fibrosis: The Fibroblast Awakens. 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