bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2019-64-1-90-98bloodjour-129Research ArticleОБЗОРЫ ЛИТЕРАТУРЫREVIEWS OF LITERATUREПЛЕЙОТРОПНЫЕ ЭФФЕКТЫ ОРАЛЬНЫХ АНТИКОАГУЛЯНТОВPLEIOTROPIC EFFECTS OF ORAL ANTICOAGULANTShttps://orcid.org/0000-0001-7403-0200ГаляутдиновГ. С.GalyautdinovG. S.

Галяутдинов Геншат Саляхутдинович, доктор медицинских наук, профессор кафедры госпитальной терапии

Genshat S. Galyautdinov, Dr. Sci. (Med.), Prof., Department of Hospital therapy

galgen077@mail.ruФейсхановаЛ. И.FeiskhanovaL. I.

Фейсханова Люция Исхаковна, кандидат медицинских наук, доцент кафедры госпитальной терапии

Feiskhanova Lucia Iskhakovna, Сand. Sci. (Med.), Assistant Prof., Department of Hospital therapy

АбдуллаевШ. П.AbdullaevSh. P.

Абдуллаев Шохрух Пардабойевич, студент лечебного факультета

Abdullaev Shokhrukh Pardaboevich, Student

ФГБОУ ВО «Казанский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияKazan State Medical UniversityRussian Federation2019100820196419098Copyright © Галяутдинов Г.С., Фейсханова Л.И., Абдуллаев Ш.П., 20192019Галяутдинов Г.С., Фейсханова Л.И., Абдуллаев Ш.П.Galyautdinov G.S., Feiskhanova L.I., Abdullaev S.P.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/129

Представлен обзор клинических исследований, целью которого была демонстрация плейотропных эффектов оральных антикоагулянтов. Плейотропный эффект прямых антикоагулянтов обусловлен взаимодействием активированного фактора свертывания крови Ха и тромбина с протеаза-активированными рецепторами -1 и -2. Рассматривается связь оральных антикоагулянтов с развитием атеросклероза, с ангиогенезом, воспалением, ремоделированием сердца, онкогенезом, гломерулярной патологией. Прямые антикоагулянты обладают антиатеросклеротическим влиянием, а именно — ослабляют прогрессию и дестабилизацию атеросклеротического поражения, о чем свидетельствует снижение активности взаимодействия ДНК с нуклеарным фактором kB и белком-активатором-1 и другими медиаторами атеросклероза и воспаления. Эффекты новых пероральных антикоагулянтов отразились и на процессах ремоделирования сердца. Ингибиторы фактора Xa способствуют замедлению ремоделирования сердца путем уменьшения процессов воспаления и фиброза за счет уменьшения экспрессии рецепторов PAR в сердце. Оральные антикоагулянты оказывают противовоспалительное действие, о чем свидетельствует уменьшение экспрессии мРНК воспалительных цитокинов под влиянием прямых антикоагулянтов, в том числе на месте атеросклеротического поражения, и снижение продукции интерлейкина-6 под действием варфарина. Ингибиторы фактора Xa усиливают экспрессию факторов роста сосудов, стимулируют миграцию эндотелиальных клеток-предшественников и улучшают их функцию, что указывает на ангиогенный плейотропный эффект. Варфарин также влияет на процессы ангиогенеза посредством уменьшения активации Axl тирозинкиназ и на гломерулярную патологию, пролиферацию мезангиальных клеток через путь Gas6/Axl. Противоопухолевая активность варфарина связана с ингибированием Gas6-опосредованной активации Axl на опухолевых клетках. Дальнейшее изучение плейотропных эффектов оральных антикоагулянтов необходимо для полного понимания последствий влияния на гемостаз. Использована литературная база PubMed и SCOPUS.

In this paper, we present a literature review with the purpose of elucidating the pleiotropic effects of oral anticoagulants. The literature search was performed using the PubMed and SCOPUS databases. Pleiotropic effects of direct anticoagulants are determined by the interaction of Xa and thrombin IIa factors with PAR-1 and PAR-2 receptors. The focus of this review is the connection between oral anticoagulants and their effects on atherosclerosis, angiogenesis, inflammation, cardiac remodelling, oncogenesis and glomerular diseases. Direct anticoagulants exhibit an anti-atherosclerotic effect manifested in a decreased progression and destabilization of atherosclerotic lesions. This effect is confirmed by a decreased binding activity of DNA with NF-kB and AP-1 transcription factors and reduced levels of some mediators. Such effects of new oral anticoagulants also relate to the processes of cardiac remodelling. FXa inhibitors contribute to the prevention of cardiac remodelling by reducing the processes of inflammation and fibrosis, which are associated with a decrease in the expression of PAR receptors in the heart. A number of studies also demonstrate an anti-inflammatory effect of oral anticoagulants, which is confirmed by reduced expression of mRNA inflammatory cytokines under the influence of direct anticoagulants and the production of IL-6 under the influence of warfarin. FXa inhibitors are shown to increase the expression of vascular growth factors, stimulate the migration of еndothelial рrogenitor сells and improve their function, thus manifesting their angiogenic pleiotropic effect. In addition, warfarin has an impact both on angiogenesis by means of reducing the activation of Axl tyrosine kinases and on glomerular pathologies by means of affecting the proliferation of mesangial cells through the Gas6/Axl pathway. The antitumour activity of warfarin is associated with inhibition of Gas6-mediated activation of Axl on tumour cells. Further investigations are required to fully understand the effect of oral anticoagulants on haemostasis.

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