medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2023.02.18-29medgen-2245Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHУровень экспрессии и структурные варианты гена толл-подобного рецептора 4 в развитии атеросклерозаThe Toll-like receptor 4 gene expression level and single nucleotide variants in the development of atherosclerosisПобожеваИ. А.PobozhevaI. A.

197101

ул. Л. Толстого, д. 6/8

Санкт-Петербург

188350

Ленинградская обл.

Гатчина

Орлова Роща

197101

6/8, L. Tolstogo str.

188350

Mkr. Orlova Rostcha, Gatchina

St. Petersburg

ДрачеваК. В.DrachevaK. V.

Ксения Владимировна Драчева

197101

ул. Л. Толстого, д. 6/8

Санкт-Петербург

188350

Ленинградская обл.

Гатчина

Орлова Роща

Ksenia V. Dracheva

197101

6/8, L. Tolstogo str.

188350

Mkr. Orlova Rostcha, Gatchina

St. Petersburg

fatal-ks@mail.ruМузалевскаяМ. В.MuzalevskayaM. V.

194291

пр. Культуры, д. 4

Санкт-Петербург

194291

4, Kultury Pr.

St. Petersburg

ПантелееваА. А.PanteleevaA. A.

197101

ул. Л. Толстого, д. 6/8

Санкт-Петербург

188350

Ленинградская обл.

Гатчина

Орлова Роща

197101

6/8, L. Tolstogo str.

188350

Mkr. Orlova Rostcha, Gatchina

St. Petersburg

УразгильдееваС. А.UrazgildeevaS. A.

194291

пр. Культуры, д. 4

199226

ул. Кораблестроителей, д. 20, к.1

Санкт-Петербург

194291

4, Kultury Pr.

191226

20-1, Korablestroiteley str.

St. Petersburg

ГуревичВ. С.GurevichV. S.

194291

пр. Культуры, д. 4

199226

ул. Кораблестроителей, д. 20, к. 1

191015

ул. Кирочная, д. 41

Санкт-Петербург

194291

4, Kultury Pr.

191226

20-1, Korablestroiteley str.

1911015

41, Kirochnaya str.

St. Petersburg

ДавыденкоВ. В.DavydenkoV. V.

197101

ул. Л. Толстого, д. 6/8

Санкт-Петербург

197101

6/8, L. Tolstogo str.

St. Petersburg

БерковичО. А.BerkovichO. A.

197101

ул. Л. Толстого, д. 6/8

Санкт-Петербург

197101

6/8, L. Tolstogo str.

St. Petersburg

БарановаЕ. И.BaranovaE. I.

197101

ул. Л. Толстого, д. 6/8

Санкт-Петербург

197101

6/8, L. Tolstogo str.

St. Petersburg

ПчелинаС. Н.PchelinaS. N.

197101

ул. Л. Толстого, д. 6/8

Санкт-Петербург

188350

Ленинградская обл.

Гатчина

Орлова Роща

197101

6/8, L. Tolstogo str.

St. Petersburg

МирошниковаВ. В.MiroshnikovaV. V.

197101

ул. Л. Толстого, д. 6/8

Санкт-Петербург

188350

Ленинградская обл.

Гатчина

Орлова Роща

197101

6/8, L. Tolstogo str.

St. Petersburg

ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской Федерации; ФГБУ «Петербургский институт ядерной физики им. Б. П. Константинова Национального исследовательского центра «Курчатовский институт»РоссияPavlov First Saint-Petersburg State Medical University; Petersburg Nuclear Physics Institute named by B. P. Konstantinov of National Research Centre «Kurchatov Institute»Russian FederationЦентр атеросклероза и нарушений липидного обмена ФГБУ «Северо-Западный окружной научно-клинический центр им. Л. Г. Соколова» ФМБА РФРоссияDepartment for Atherosclerosis and Lipid Disorders of North-Western district scientific and clinical center named after L. G. Sokolov, Federal Medical and Biological Agency”Russian FederationЦентр атеросклероза и нарушений липидного обмена ФГБУ «Северо-Западный окружной научно-клинический центр им. Л. Г. Соколова» ФМБА РФ; Научно-клинический и образовательный центр «Кардиология» Санкт-Петербургского государственного университетаРоссияDepartment for Atherosclerosis and Lipid Disorders of North-Western district scientific and clinical center named after L. G. Sokolov, Federal Medical and Biological Agency”; Scientific, clinical and educational center “Cardiology” of Saint-Petersburg State UniversityRussian FederationЦентр атеросклероза и нарушений липидного обмена ФГБУ «Северо-Западный окружной научно-клинический центр им. Л. Г. Соколова» ФМБА РФ; Научно-клинический и образовательный центр «Кардиология» Санкт-Петербургского государственного университета; Северо-западный государственный медицинский университет им. И. И. МечниковаРоссияDepartment for Atherosclerosis and Lipid Disorders of North-Western district scientific and clinical center named after L. G. Sokolov, Federal Medical and Biological Agency”; Scientific, clinical and educational center “Cardiology” of Saint-Petersburg State University; North-Western State Medical University named after I. I. MechnikovRussian FederationФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской ФедерацииРоссияPavlov First Saint-Petersburg State Medical UniversityRussian FederationФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И. П. Павлова» Министерства здравоохранения Российской Федерации; ФГБУ «Петербургский институт ядерной физики им. Б. П. Константинова Национального исследовательского центра «Курчатовский институт»РоссияPavlov First Saint-Petersburg State Medical UniversityRussian Federation2023100420232221829Copyright © Побожева И.А., Драчева К.В., Музалевская М.В., Пантелеева А.А., Уразгильдеева С.А., Гуревич В.С., Давыденко В.В., Беркович О.А., Баранова Е.И., Пчелина С.Н., Мирошникова В.В., 20232023Побожева И.А., Драчева К.В., Музалевская М.В., Пантелеева А.А., Уразгильдеева С.А., Гуревич В.С., Давыденко В.В., Беркович О.А., Баранова Е.И., Пчелина С.Н., Мирошникова В.В.Pobozheva I.A., Dracheva K.V., Muzalevskaya M.V., Panteleeva A.A., Urazgildeeva S.A., Gurevich V.S., Davydenko V.V., Berkovich O.A., Baranova E.I., Pchelina S.N., Miroshnikova V.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.medgen-journal.ru/jour/article/view/2245

   В настоящее время атеросклероз рассматривается как хроническое воспалительное заболевание, характеризующееся нарушением функции эндотелия сосудистой стенки, миграцией иммунных клеток, субэндотелиальным накоплением липидов и пролиферацией гладкомышечных клеток сосудов с дальнейшим образованием атеросклеротической бляшки. Исследования предполагают потенциальную важность толл-подобных рецепторов (TLRs) и других ключевых компонентов врожденной иммунной системы в патологических состояниях, связанных с атеросклерозом. Толл-подобный рецептор 4 (TLR4) может играть ключевую роль в иммунопатогенезе атеросклероза.

   Целью данной работы было исследование ассоциации экспрессии гена TLR4 в макрофагах и полиморфных вариантов rs4986790 и rs4986791 с развитием атеросклероза в популяции Санкт-Петербурга.

   В исследование были включены 220 пациентов с атеросклерозом различной локализации (коронарный, церебральный, артерий нижних конечностей); 75 пациентов с семейной гиперхолестеринемией с / без проявлений атеросклероза; 376 лиц без сердечно-сосудистой патологии (контрольная группа). Генотипирование полиморфных вариантов гена TLR4 было выполнено методом ПЦР с последующим рестрикционным анализом. Сравнительный анализ уровня экспрессии гена TLR4 в дифференцированных in vitro макрофагах был выполнен у пациентов с коронарным атеросклерозом (n = 13) и представителей контрольной группы (n = 19) методом ПЦР в реальном времени. Для пациентов с коронарным атеросклерозом характерен более высокий уровень экспрессии гена TLR4 в макрофагах, чем в контрольной группе. Структурные варианты Asp299Gly и Thr399Ile гена TLR4 не ассоциированы с развитием атеросклероза у жителей Санкт-Петербурга, в том числе у пациентов с семейной гиперхолестеринемией.

   Atherosclerosis is considered as a chronic inflammatory disease characterized by dysfunction of the endothelium of the vascular wall, migration of immune cells, subendothelial accumulation of lipids and proliferation of vascular smooth muscle cells with further formation of atherosclerotic plaques. Research data suggests the potential importance of Toll-like receptors (TLRs) and other key components of the innate immune system in the pathologies associated with atherosclerosis. Toll-like receptor 4 (TLR4) may play a key role in the immunopathogenesis of atherosclerosis.

   The aim of this study was to explore the association of TLR4 gene expression in macrophages and polymorphic variants rs4986790 and rs4986791 with the development of atherosclerosis in the St. Petersburg population.

   The study included 671 individuals: 220 patients with atherosclerosis of various localizations (coronary, cerebral, lower extremity artery pool); 75 patients with familial hypercholesterolemia with/without manifestation of atherosclerosis; 376 individuals without cardiovascular pathology as the control group. Genotyping of polymorphic variants of the TLR4 gene was performed by PCR followed by restriction analysis. Analysis of the TLR4 gene expression level in was performed in differentiated in vitro macrophages of 13 patients with coronary atherosclerosis and 19 representatives of the control group by real-time PCR. Patients with coronary atherosclerosis were characterized by an increased level of TLR4 gene expression in macrophages when compared with the control group. The Asp299Gly and Thr399Ile variants of the TLR4 gene were not associated with atherosclerosis development in the population of St. Petersburg, including patients with familial hypercholesterolemia.

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