mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-CEP-2869mimmun-2869Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESОценка локального профиля цитокинов, экспрессируемых нативными клапанами сердца, полученными от пациентов с инфекционным эндокардитомCytokine expression profile of native heart valves obtained from patients with infective endocarditisСиницкаяА. В.SinitskayaA. V.

Синицкая А.В. – к.б.н., научный сотрудник лаборатории геномной медицины отдела экспериментальной медицины 

г. Кемерово

Sinitskaya A.V., PhD (Biology), Research Associate, Laboratory of Genomic Medicine, Department of Experimental Medicine 

Kemerovo

cepoav1991@gmail.comСиницкийМ. Ю.SinitskyM. Yu.

Синицкий М.Ю. – к.б.н., старший научный сотрудник лаборатории геномной медицины отдела экспериментальной медицины 

г. Кемерово

Sinitsky M.Yu., PhD (Biology), Senior Research Associate, Laboratory of Genomic Medicine, Department of Experimental Medicine 

Kemerovo

КазачекЯ. В.KazachekYa. V.

Казачек Я.В. – к.м.н., главный фармаколог

г. Кемерово

Kazachek Ya.V., PhD (Medicine), Chief Pharmacologist 

Kemerovo

ЕвтушенкоА. В.EvtushenkoA. V.

Евтушенко А.В. – д.м.н., заведующий лабораторией пороков сердца 

г. Кемерово

Evtushenko A.V., PhD, MD (Medicine), Head, Laboratory of Heart Diseases, Department of heart and vascular surgery 

Kemerovo

ХуторнаяМ. В.KhutornayaM. V.

Хуторная М.В. – младший научный сотрудник лаборатории геномной медицины отдела экспериментальной медицины 

г. Кемерово

Khutornaya M.V., Junior Research Associate, Laboratory of Genomic Medicine, Department of Experimental Medicine 

Kemerovo

АсановМ. А.AsanovM. A.

Асанов М.А. – младший научный сотрудник лаборатории геномной медицины отдела экспериментальной медицины 

г. Кемерово

Asanov M.A., Junior Research Associate, Laboratory of Genomic Medicine, Department of Experimental Medicine 

Kemerovo

ПоддубнякА. О.PoddubnyakA. O.

Поддубняк А.О. – лаборант-исследователь лаборатории геномной медицины отдела экспериментальной медицины 

г. Кемерово

Poddubnyak A.O., Research Laboratory Assistant, Laboratory of Genomic Medicine, Department of Experimental Medicine 

Kemerovo

ПонасенкоА. В.PonasenkoA. V.

Понасенко А.В. – к.м.н., заведующая лабораторией геномной медицины отдела экспериментальной медицины 

г. Кемерово

Ponasenko A.V., PhD (Medicine), Head, Laboratory of Genomic Medicine, Department of Experimental Medicine 

Kemerovo

ФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний»РоссияResearch Institute for Complex Issues of Cardiovascular DiseasesRussian Federation20241610202326612231234Copyright © Синицкая А.В., Синицкий М.Ю., Казачек Я.В., Евтушенко А.В., Хуторная М.В., Асанов М.А., Поддубняк А.О., Понасенко А.В., 20242024Синицкая А.В., Синицкий М.Ю., Казачек Я.В., Евтушенко А.В., Хуторная М.В., Асанов М.А., Поддубняк А.О., Понасенко А.В.Sinitskaya A.V., Sinitsky M.Y., Kazachek Y.V., Evtushenko A.V., Khutornaya M.V., Asanov M.A., Poddubnyak A.O., Ponasenko A.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2869

Инфекционный эндокардит характеризуется дисфункцией клапанов сердца и вносит значительный вклад в структуру заболеваемости и смертности среди всех патологий сердечно-сосудистой системы. Иммунный ответ играет важную роль в патофизиологии данного заболевания. Структурные модификации в генах, кодирующих молекулы, вовлеченные в иммунный ответ, а также изменение их экспрессии, могут приводит к изменению функциональной активности и количества синтезируемых белков, что, в свою очередь, оказывает влияние на эффективности иммунного ответа. Целью исследования стала оценка локального профиля цитокинов, экспрессируемых нативными клапанами сердца, полученными от пациентов с инфекционным эндокардитом в процессе кардиохирургического вмешательства. Профиль секретируемых цитокинов изучали в нативных клапанах сердца, полученных от 4 пациентов с инфекционным эндокардитом (экспериментальная группа) и 10 пациентов с ревматической болезнью сердца (контрольная группа) методом дот-блоттинга с использованием наборов Proteome Profiler™ Human Cytokine Array Kit (ARY005B). Результаты дот-блоттинга подтверждали путем оценки уровня экспрессии соответствующих генов с помощью количественной полимеразной цепной реакции после обратной транскрипции с использованием праймеров, синтезированных компанией «Евроген» (Москва, Россия). Белки MIF, PAI-1, ICAM-1 и CXCL12 обнаружены в образцах нативных клапанов как экспериментальной, так и контрольной групп. В результате полуколичественного анализа установлено, что клапаны, пораженные инфекционным эндокардитом, характеризовались четырехкратным повышением секреции PAI-1 и двухкратным снижением секреции молекул ICAM-1 и CXCL12 по сравнению с контрольной группой. MIF экспрессировался на одном и том уже уровне в обеих изученных группах. Белки IL-1ra, IL-6, IL-8, IL-16, CCL4, CCL5 и CXCL1 обнаружены только в клапанах, пораженных инфекционным эндокардитом. Кроме того, показано, что экспериментальная группа характеризовалась повышением экспрессии генов MIF, IL6, IL8; а также снижением уровня мРНК генов PAI1, IL1RA и CXCL1 относительно контроля. Таким образом, нативные клапаны сердца, пораженные инфекционным эндокардитом, характеризуются развитием локального воспаления, вызванного патогенной бактериемией, и активной неоваскуляризацией. 

Infectious endocarditis is characterized by dysfunction of heart valves and contribute significantly to the cardiovascular morbidity and mortality worldwide, especially in low- and middle-income countries. Immune response is playing the important role in the pathophysiology of this disease. This work was aimed to study the local cytokine profile in native heart valves obtained from the patients with infectious endocarditis. Cytokine profiling were performed in biopsies of native heart valves explanted from 4 patients with infective endocarditis (experimental group) and 10 patients with rheumatic heart disease (comparison group) by dot blotting using the Proteome Profiler™ Human Cytokine Array Kit (ARY005B). The results of dot blotting were validated by the gene expression profiling using quantitative polymerase chain reaction. MIF, PAI-1, ICAM-1 and CXCL12 were found in the native heart valves explanted from both infective endocarditis and rheumatic heart disease patients. Upon a semi-quantitative assessment, the heart valves explanted from the infective endocarditis patients were characterized by 4-fold increased secretion of PAI-1 and twofold decreased secretion of ICAM-1 and CXCL12 compared to the heart valves ffected by rheumatic heart disease. MIF was expressed on similar levels in the both studied groups. IL-1ra, IL-6, IL-8, IL-16, CCL4, CCL5 and CXCL1 were detected only in heart valves affected by infectious endocarditis. At the gene expression level, MIF, IL6, IL8 genes were upregulated and PAI1, IL1RA, CXCL1 genes were downregulated in heart valves explanted from infectious endocarditis patients compared to the subjects affected by rheumatic heart disease. Native heart valves in cases of infectious endocarditis are characterized by nonspecific local inflammatory response associated with pathogenic bacteremia, along with active neovascularization. The data obtained can help to better understand fundamental pathogenetic mechanisms of infectious endocarditis.

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The authors declare that there are no conflicts of interest present.