arthyperАртериальная гипертензия"Arterial’naya Gipertenziya" ("Arterial Hypertension")1607-419X2411-8524Antihypertensive League10.18705/1607-419X-2026-2611FNSICYarthyper-2611Research ArticleСтатьиArticlesУровень длинной некодирующей РНК LIRIL2R при эссенциальной артериальной гипертензии: возможная связь с изоформами сплайсинга мРНК гена FOXP3The long non-coding RNA LIRIL2R level in essential arterial hypertension: possible association with the FOXP3 mRNA splicing isoformshttps://orcid.org/0000-0001-8697-2086ТопчиеваЛ. В.TopchievaL. V.

Топчиева Людмила Владимировна — кандидат биологических наук, руководитель лаборатории генетики

ул. Пушкинская, д. 11, Петрозаводск, 185910

Тел.: +7 (814) 57-31-07

Lyudmila V. Topchieva, PhD in Biology Sciences, Head, Genetics Laboratory

11 Pushkinskaya str., Petrozavodsk, 185910

Phone: +7 (814) 57-31-07

topchieva67@mail.ruhttps://orcid.org/0000-0001-7620-7065КурбатоваИ. В.KurbatovaI. V.

Курбатова Ирина Валерьевна — кандидат биологических наук, старший научный сотрудник лаборатории генетики 

Петрозаводск

Irina V. Kurbatova, PhD in Biology Sciences, Senior Researcher, Genetics Laboratory

Petrozavodsk

irina7m@yandex.ruhttps://orcid.org/0000-0003-2231-4695КорневаВ. А.KornevaV. A.

Корнева Виктория Алексеевна — кандидат медицинских наук, доцент кафедры факультетской терапии, фтизиатрии, инфекционных болезней и эпидемиологии

Петрозаводск

Viktoria A. Korneva, MD, PhD, Associate Professor, Department of Therapy, Phthisiology, Infectious Diseases and Epidemiology

Petrozavodsk

vikkorneva@mail.ruФедеральное государственное бюджетное учреждение науки Федеральный исследовательский центр «Карельский научный центр Российской академии наук»РоссияKarelian Research Centre of the Russian Academy of SciencesRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Петрозаводский государственный университет»РоссияPetrozavodsk State UniversityRussian Federation202625092026323292301Copyright © Топчиева Л.В., Курбатова И.В., Корнева В.А., 20262026Топчиева Л.В., Курбатова И.В., Корнева В.А.Topchieva L.V., Kurbatova I.V., Korneva V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://htn.almazovcentre.ru/jour/article/view/2611

Цель исследования — оценить содержание длинной некодирующей РНК (днРНК) LIRIL2R в лейкоцитах периферической крови (ЛПК) и его связь с уровнем интерлейкина 2 (ИЛ-2), количеством изоформ сплайсинга мРНК гена FOXP3 при эссенциальной артериальной гипертензии (ЭАГ). Материалы и методы. В исследование включены условно здоровые люди (25 человек) и пациенты с диагнозом ЭАГ (I– II стадии) до назначения антигипертензивных препаратов (17 человек) и принимающие кардиоселективные блокаторы β-адренорецепторов более года (метопролол 25 мг/сут или бисопролол 5–10 мг/сут) (21 человек). Уровень транскриптов генов оценивали методом полимеразной цепной реакции (ПЦР) в режиме реального времени. Содержание ИЛ-2 определяли методом иммуноферментного анализа (ИФА). Статистическая обработка результатов проводилась с использованием пакета программ Statgraphics Centurion XVI (version 16.1.11), GraphPad Prism v. 7 (США). Результаты. Относительный уровень транскриптов LIRIL2R в ЛПК больных ЭАГ (группа больных до назначения антигипертензивной терапии и группа лиц, принимающих кардиоселективные блокаторы β-адренорецепторов) был выше, чем у здоровых людей (p < 0,05). Относительное содержание транскриптов полноразмерной формы мРНК FOXP3 (FOXP3FL), изоформы без экзона 2 (FOXP3Δ2) и формы с включенным экзоном 2 (FOXP3e2) оказался выше в ЛПК пациентов без антигипертензивной терапии при сравнении со здоровыми людьми и пациентами на терапии (p < 0,05). В ЛПК больных ЭАГ, не принимавших ранее антигипертензивных препаратов, преобладающими были FOXP3Δ2 транскрипты (FOXP3Δ2/FOXP3e2 – 1,3). В ЛПК здоровых индивидов и пациентов на терапии было больше транскриптов с включенным экзоном 2 (FOXP3Δ2/FOXP3e2 составило 0,4 и 0,12 соответственно). В группе здоровых людей уровень LIRIL2R в ЛПК отрицательно коррелировал с количеством транскриптов FOXP3Δ2 (r = −0,63; p = 0,029). Содержание ИЛ-2 в плазме крови пациентов с ЭАГ до назначения антигипертензивной терапии было значимо выше, чем у пациентов, принимающих метопролол или бисопролол, и у здоровых людей (p < 0,05). Выявлена связь количества LIRIL2R транскриптов с содержанием ИЛ-2 в плазме крови пациентов с ЭАГ без антигипертензивной терапии (r = 0,85; p = 0,024). В этой же группе обследованных уровень экспрессии LIRIL2R положительно коррелировал с относительным содержанием транскриптов FOXP3Δ2 и FOXP3e2 (r = 0,99; p = 0,027 в обоих случаях). Уровень LIRIL2R положительно коррелировал с содержанием растворимой формы молекулы межклеточной адгезии-1 (r = 0,528; p = 0,013) и малонового диальдегида (r = 0,548; p = 0,004). Заключение. Повышение содержания LIRIL2R транскриптов в ЛПК больных ЭАГ связано с изменением соотношения альтернативно сплайсированных форм мРНК гена FOXP3 и увеличением уровня растворимой формы молекулы межклеточной адгезии и малонового диальдегида, что указывает на ее вероятное вовлечение в регуляцию уровня воспаления при данном заболевании.

The aim of the study was to evaluate the content of the LIRIL2R of the long non-coding RNA (lncRNA) in peripheral blood leukocytes (PBL) and its relationship with interleukin 2 (IL-2) levels and the number of the FOXP3 mRNA splicing isoforms in patients with essential arterial hypertension (EAH). Design and methods. The study included 25 healthy individuals and 17 patients diagnosed with EAH (stages I–II) before antihypertensive therapy and 21 patients taking cardioselective β-blockers (metoprolol 25 mg/day or bisoprolol 5– 10 mg/day) for more than a year. The level of gene transcripts was assessed by real-time polymerase chain reaction (PCR). The content of IL-2 was determined by the ELISA. Statistical processing of the results was carried out in the Statgraphics Centurion XVI (version 16.1.11) and the GraphPad Prism v. 7 software packages (USA). Results. The relative level of the LIRIL2R transcripts in PBL of EAH patients (a group of patients before antihypertensive therapy and a group of patients taking cardioselective beta-blockers) was higher than in healthy people (p < 0,05). The relative transcript content of the full-length form of the FOXP3 mRNA (FOXP3FL), the isoform lacking exon 2 (FOXP3Δ2), and the form with included exon 2 (FOXP3e2) was higher in PBL of patients without antihypertensive therapy when compared with healthy individuals and patients on therapy (p < 0,05). In PBL of EAH patients who had not previously taken antihypertensive drugs, the FOXP3Δ2 transcripts were predominant (FOXP3Δ2/FOXP3e2 – 1,3). In PBL of healthy individuals and patients on therapy, there were more transcripts with included exon 2 (FOXP3Δ2/FOXP3e2 was 0,4 and 0,12, respectively). In the group of healthy individuals, the LIRIL2R level in PBL negatively correlated with the amount of the FOXP3Δ2 transcripts (r = −0,63; p = 0,029). The IL-2 content in the plasma of EAH patients before antihypertensive therapy was significantly higher than in patients taking metoprolol or bisoprolol, and in healthy individuals (p < 0,05). A relationship between the amount of the LIRIL2R transcripts and the IL-2 content in the plasma of EAH patients without antihypertensive therapy was found (r = 0,85; p = 0,024). In the same group of subjects, the level of the LIRIL2R expression positively correlated with the relative content of the FOXP3Δ2 and FOXP3e2 transcripts (r = 0,99; p = 0,027 in both cases). The LIRIL2R levels positively correlated with soluble form of the intercellular adhesion molecule (sICAM) (r = 0,528; p = 0,013) and malondialdehyde (MDA) (r = 0,548; p = 0,004) levels. Conclusion. The increased LIRIL2R transcript levels in PBL of EAH patients are associated with a change in the ratio of alternatively spliced forms of the FOXP3 gene mRNA and an increase in the levels of sICAM and MDA, indicating its likely involvement in the regulation of inflammation in EAH.

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