fcmedicineФундаментальная и клиническая медицинаFundamental and Clinical Medicine2500-07642542-0941КемГМУ10.23946/2500-0764-2024-9-4-95-106fcmedicine-947Research ArticleОБЗОРНЫЕ СТАТЬИREVIEW ARTICLESВлияние факторов риска сердечно-сосудистых заболеваний на морфофункциональные свойства мезенхимальных стволовых клетокThe influence of risk factors for cardiovascular diseases on the morphofunctional properties of mesenchymal stem cellshttps://orcid.org/0000-0003-0749-4093СлесареваТ. А.SlesarevaT. A.

Слесарева Тамара Александровна, аспирант кафедры патологической физиологии

650056, г. Кемерово, ул. Ворошилова, д. 22а

Dr. Tamara A. Slesareva, MD, PhD Student, Pathological physiology Department

22a, Voroshilova Street, Kemerovo, 650056

soloveva081296@mail.ruhttps://orcid.org/0000-0003-4321-8977УчасоваЕ. Г.UchasovaE. G.

Евгения Геннадьевна Учасова, кандидат медицинских наук, старший научный сотрудник лаборатории исследований гомеостаза

650002, Кемерово, бульвар им. академика Леонида Барбараша, стр. 6

Dr. Evgenia G. Uchasova, MD, PhD, Senior Researcher at the Laboratory of Homeostasis

6, Аcademician Leonid Barbarash blvd., Kemerovo, 650002

https://orcid.org/0000-0002-6890-3287ДылеваЮ. А.DylevaYu. A.

Дылева Юлия Александровна, кандидат медицинских наук, старший научный сотрудник лаборатории исследований гомеостаза отделения диагностики сердечно-сосудистых заболеваний

650002, Кемерово, бульвар им. академика Леонида Барбараша, стр. 6

Dr. Yuliya A. Dyleva, MD, PhD, Senior Researcher at the Laboratory of Homeostasis Research

6, Аcademician Leonid Barbarash blvd., Kemerovo, 650002

https://orcid.org/0000-0003-3996-3325БеликЕ. В.BelikE. V.

Екатерина Владимировна Белик, кандидат медицинских наук, старший научный сотрудник лаборатории исследований гомеостаза

650002, Кемерово, бульвар им. академика Леонида Барбараша, стр. 6

Dr. Ekaterina V. Belik, MD, PhD, Senior Researcher at the Laboratory of Homeostasis Research

6, Аcademician Leonid Barbarash blvd., Kemerovo, 650002

https://orcid.org/0000-0002-7780-829XГруздеваО. В.GruzdevaO. V.

Груздева Ольга Викторовна, доктор медицинских наук, профессор РАН, заведующая лабораторией исследования гомеостаза; заведующая кафедрой медицинской биохимии

650002, Кемерово, бульвар им. академика Леонида Барбараша, стр. 6

650056, г. Кемерово, ул. Ворошилова, д. 22а

Prof. Olga V. Gruzdeva, MD, DSc, Professor of the Russian Academy of Sciences, Head of the Laboratory of Homeostasis Research; Head of the Medical Biochemistry Department

6, Аcademician Leonid Barbarash blvd., Kemerovo, 650002

22a, Voroshilova Street, Kemerovo, 650056

ФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний»; ФГБОУ ВО «Кемеровский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияResearch Institute for Complex Issues of Cardiovascular Diseases; Kemerovo State Medical UniversityRussian FederationФГБНУ «Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний»РоссияResearch Institute for Complex Issues of Cardiovascular DiseasesRussian Federation2024251220249495106Copyright © Слесарева Т.А., Учасова Е.Г., Дылева Ю.А., Белик Е.В., Груздева О.В., 20242024Слесарева Т.А., Учасова Е.Г., Дылева Ю.А., Белик Е.В., Груздева О.В.Slesareva T.A., Uchasova E.G., Dyleva Y.A., Belik E.V., Gruzdeva O.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://fcm.kemsmu.ru/jour/article/view/947

На сегодняшний день активно обсуждается вклад мезенхимальных стволовых клеток (МСК) в механизм развития таких патологий, как кальцификация клапанов сердца и сосудов.О бусловлено это тем, что образование кальцинатов в сердечно-сосудистой системе (ССС) повторяет процесс оссификации, то есть опосредован специфическими костными клетками – остеоцитами. Так как МСК являются клетками-предшественниками, способными к мультилинейной дифференцировке, их рассматривают как источник остеоцитов в ССС. Вопрос о том, какие стимулы активируют программу остеогенеза в МСК, локализующихся в органах ССС, остается открытым. Наличие факторов риска сердечно-сосудистых заболеваний (ССЗ) оказывает системное воздействие на организм, так как они способствуют развитию таких патологических процессов, как гипоксия и воспаление, приводящих к ремоделированию ниши МСК и изменению их функции. В данном обзоре систематизированы научные исследования, посвященные влиянию модифицируемых и немодифицируемых факторов риска ССЗ на морфофункциональные свойства МСК.

Целью данного обзора является систематизация имеющихся знаний о роли модифицируемых и немодифицируемых факторов риска ССЗ в изменении морфологии и функции МСК.

Функционирование МСК зависит от возраста донора и длительности их культивирования in vitro за счет активации процессов клеточного старения. Влияние пола на МСК неоднозначно описано в литературе, однако есть данные об участии эстрогена в регулировании баланса между остеогенной и адипогенной дифференцировкой клеток-предшественников. Наличие таких коморбидных состояний, как гиперхолестеринемия, ожирение, сахарный диабет, способствует ускорению клеточного старения, модификации фенотипа МСК, оказывает влияние на активность их пролиферации и потенциал дифференцировки. Так, комплекс патологических процессов, сопровождающих ожирение и сахарный диабет, приводит к снижению дифференцированного потенциала МСК, а также индуцирует экспрессию генов-маркеров клеточного старения. Увеличение концентрации эфиров холестерола в микроокружении МСК индуцирует в них программу остеогенной дифференцировки, а воздействие липопротеинов высокой плотности (ЛПВП) положительно влияет на пролиферацию. Сигаретный дым активирует апоптоз стволовых клеток, снижает пролиферацию и индуцирует остеогенез.

Today, the contribution of mesenchymal stem cells (MSCs) to the mechanism of development of pathologies such as calcification of heart valves and blood vessels is being actively discussed. This is due to the fact that the formation of calcifications in the cardiovascular system (CVS) repeats the process of ossification, that is, it is mediated by specific bone cells - osteocytes. Since MSCs are progenitor cells capable of multilineage differentiation, they are considered as a source of osteocytes in the cardiovascular system. The question of what stimuli activate the osteogenesis program in MSCs localized in the CVS organs remains open. The presence of risk factors for cardiovascular diseases (CVD) has a systemic effect on the body, as it contributes to the development of pathological processes such as hypoxia and inflammation, which lead to remodeling of the MSC niche and changes in their function. This review systematizes scientific studies devoted to the influence of modifiable and non-modifiable CVD risk factors on the morphofunctional properties of MSCs.

The purpose of this review is to systematize existing knowledge about the role of modifiable and non-modifiable CVD risk factors in changing the morphology and function of MSCs.

The functioning of MSCs depends on the age of the donor and the duration of their cultivation in vitro, due to the activation of cellular aging processes. The influence of gender on MSCs is controversially described in the literature; however, there is evidence of the participation of estrogen in regulating the balance between osteogenic and adipogenic differentiation of progenitor cells. The presence of comorbid conditions such as hypercholesterolemia, obesity, and diabetes mellitus contribute to the acceleration of cellular aging, modification of the MSC phenotype, and influence the activity of their proliferation and differentiation potential. Thus, the complex of pathological processes accompanying obesity and diabetes mellitus leads to a decrease in the differentiated potential of MSCs, and also induces the expression of genes that are markers of cellular aging. An increase in the concentration of cholesterol esters in the microenvironment of MSCs induces a program of osteogenic differentiation in them, and exposure to high density lipoproteins (HDL) has a positive effect on proliferation. Cigarette smoke activates stem cell apoptosis, reduces proliferation, and induces osteogenesis.

мезенхимальные стволовые клеткифакторы рискасердечно-сосудистые заболеваниякоморбидные состоянияmesenchymal stem cellsrisk factorscardiovascular diseasescomorbid conditionsРабота выполнена в рамках фундаментальной темы 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».The study was supported within the framework of the Fundamental Topic of the Research Institute for Complex Issues of Cardiovascular Diseases No. 0419-2022-0002 entitled “Development of innovative models for management of cardiovascular disease risk factors and comorbidities based on the study of fundamental, clinical, and epidemiological mechanisms and healthcare management techniques in the industrial region of Siberia”.ReferencesХарченко В.В., Иванов В.А., Ветров А.О. 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The authors declare that there are no conflicts of interest present.