medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2024-4-7-11medalphabet-3657Research ArticleСтатьиВозможности проточной цитометрии, ПЦР и секвенирования в ранней диагностике активности атеросклероза (обзор литературы)Possibilities of flow cytometry, PCR and sequencing in early diagnosis of atherosclerosis activityhttps://orcid.org/0000-0003-2592-6857РойтманА. П.RoytmanA. P.

Ройтман Александр Польевич, д. м. н., профессор кафедры клинической лабораторной диагностики с курсом лабораторной иммунологии

Москва

Roitman Alexander P., DM Sci (habil.), professor at Dept of Clinical Laboratory Diagnostics with a course in Laboratory Immunology

Moscow

aroitman@mail.ruhttps://orcid.org/0000-0001-8458-9702МаркинаН. С.MarkinaN. S.

Маркина Надежда Сергеевна, ординатор кафедры клинической лабораторной диагностики с курсом лабораторной иммунологии

Москва

Markina Nadezhda S., resident of Dept of Clinical Laboratory Diagnostics with a course in laboratory immunology

Moscow

nadezda.s.markina@gmail.comhttps://orcid.org/0000-0003-1537-7444ДолговВ. В.DolgovV. V.

Долгов Владимир Владимирович, д. м. н., профессор кафедры клинической лабораторной диагностики с курсом лабораторной иммунологии

Москва

Dolgov Vladimir V., Doctor of Medical Sciences, professor at Dept of Clinical Laboratory Diagnostics with a course in Laboratory Immunology

Moscow

vvdolgov@inbox.ruФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииРоссияRussian Medical Academy of Continuous Professional EducationRussian Federation20240805202404Современная лаборатория (1)711Copyright © Ройтман А.П., Маркина Н.С., Долгов В.В., 20242024Ройтман А.П., Маркина Н.С., Долгов В.В.Roytman A.P., Markina N.S., Dolgov 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.med-alphabet.com/jour/article/view/3657

Атеросклероз (АС) является многофакторным заболеванием, приводящим к повышению сердечно-сосудистых рисков. В настоящее время диагностика АС сводится к визуализирующим методам оценки атеросклеротической бляшки и лабораторным методам диагностики дислипидемий, которые не дают понимания активности процессов, происходящих в атеросклеротической бляшке. Цель данного обзора: обсудить потенциальные лабораторные маркёры активности АС. Важная роль в атерогенезе отводится макрофагам. Макрофаги имеют несколько фенотипов, определив которые можно сделать заключение об активности воспалительного процесса в бляшке. Не малую роль в развитии атеросклероза играют генетические маркёры, такие как микроРНК, кольцевые РНК и факторы, регулирующие их экспрессию. Перспективными для изучения данных маркёров являются методы проточной цитометрии, ПЦР и секвенирования. Маркёры активности атерогенеза являются необходимыми в диагностике, а также при выборе персонализированного лечения пациентов.

Atherosclerosis (AS) is a multifactorial disease leading to increased cardiovascular risks. Currently, the diagnosis of AS is limited to imaging methods of atherosclerotic plaque assessment and laboratory methods of dyslipidemia diagnosis, which do not provide an understanding of the activity of processes occurring in the atherosclerotic plaque. The aim of this review: to generate potential markers of AS activity. Macrophages play an important role in atherogenesis. Macrophages have several phenotypes, determining which can be concluded about the activity of the inflammatory process in the plaque. Genetic markers, such as microRNAs, circular RNAs and factors regulating their expression, play an important role in the development of atherosclerosis. Methods of flow cytometry, PCR and sequencing are promising for studying these markers. Markers of atherogenesis activity are essential in diagnosis, as well as in the choice of personalized treatment of patients.

атеросклерозмакрофагимикроРНКкольцевые РНКцитометрииПЦРсеквенированиеatherosclerosismacrophagesmicroRNAscircular RNAscytometryPCRsequencingReferencesКузьмичев Д. Е., Скребов Р. В. Клиника, морфология атеросклероза аорты с разрывом. Здравоохранение Югры: опыт и инновации. 2018; (4): 66–8. https://cyberleninka.ru/article/n/klinika-morfologiya-ateroskleroza-aorty-s-razryvomKuzmichev D. E., Skrebov R. V. Clinic, morphology of aortic atherosclerosis with rupture. Healthcare of Ugra: experience and innovations. 2018; (4): 66–8. https://cyberleninka.ru/article/n/klinika-morfologiya-ateroskleroza-aorty-s-razryvomКузнецов С. Н., Мушкамбаров Н. Н. Гистология, цитология и эмбриология. МИА (Медицинское информационное агентство); 2016: 640.Kuznetsov S. N., Mushkambarov N. N. Histology, cytologyandembryology. MIA (Medical Information Agency); 2016: 640.Haverich A., Boyle E. C. Atherosclerosis Pathogenesis and Microvascular Dysfunction. Cham: Springer Nature; 2019. 130. https://doi.org/10.1007/978–3–030–20245–3Haverich A., Boyle E. C. Atherosclerosis Pathogenesis and Microvascular Dysfunction. Cham: Springer Nature; 2019. 130. https://doi.org/10.1007/978–3–030–20245–3Юрьева Э. А., Сухоруков В. С., Воздвиженская Е. С., Новикова Н. Н. Атеросклероз: гипотезыитеории. Российский вестник перинатологии и педиатрии. 2014; 59(3): 6–16. https://www.elibrary.ru/item.asp?id=21649590Yuryeva E. A., Sukhorukov V. S., Vozdvizhenskaya E. S., Novikova N. N. Atherosclerosis: hypothesesandtheories. Russian Bulletin of Perinatology and Pediatrics. 2014; 59(3): 6–16. https://www.elibrary.ru/item.asp?id=21649590Орищенко А. К., Гавриченко Е. П., Райкова К. А. Совеременные теории этиологии и патогенеза атеросклероза. Бюллетень медицинских интернет-конференций. 2021;11(3):57–57. ID: 2021–03–6-T-19461Orishchenko A. K., Gavrichenko E. P., Raikova K. A. Modern theories of the etiology and pathogenesis of atherosclerosis. Bulletin of Medical Internet Conferences. 2021; 11(3): 57–57. ID: 2021–03–6-T-19461Слепцов А. А. Клеточная гетерогенность и клональный гемопоэз клеток иммунной системы при атеросклерозе. Российскийкардиологическийжурнал. 2022;27(10):5228. https://doi.org/10.15829/1560–4071–2022–5228Sleptsov A. A. Cellular heterogeneity and clonal hematopoiesis of immune system cells in atherosclerosis. Russian Journal of Cardiology. 2022; 27(10): 5228. https://doi.org/10.15829/1560–4071–2022–5228Xu J., Lu X., Shi G. P. Vasa Vasorum in Atherosclerosis and Clinical Significance. Int J Mol Sci. 2015;16(5):11574–608. https://doi.org/10.3390/ijms160511574Xu J., Lu X., Shi G. P. Vasa Vasorum in Atherosclerosis and Clinical Significance. Int J Mol Sci. 2015;16(5):11574–608. https://doi.org/10.3390/ijms160511574Rademakers T., Douma K., Hackeng T. M., Post M. J., Sluimer J. C., Daemen идр. Plaque-Associated Vasa Vasorum in Aged Apolipoprotein E–Deficient Mice Exhibit Proatherogenic Functional Features In Vivo. Arteriosclerosis, Thrombosis, and Vascular Biology. 2013;33(2):249–56. https://doi.org/10.1161/ATVBAHA.112.300087Rademakers T., Douma K., Hackeng T. M., Post M. J., Sluimer J. C., Daemen идр. Plaque-Associated Vasa Vasorum in Aged Apolipoprotein E–Deficient Mice Exhibit Proatherogenic Functional Features In Vivo. Arteriosclerosis, Thrombosis, and Vascular Biology. 2013;33(2):249–56. https://doi.org/10.1161/ATVBAHA.112.300087Евдокименко А. Н., Куличенкова К. Н., Гулевская Т. С., Танашян М. М. Особенности регуляции ангиогенеза в атеросклеротических бляшках каротидного синуса на поздних стадиях развития атеросклероза. Российский физиологический журнал им И. М. Сеченова. 2022;108(5):649–66. https://doi.org/10.31857/S0869813922050041Evdokimenko A. N., Kulichenkova K. N., Gulevskaya T. S., Tanashyan M. M. Features of the regulation of angiogenesis in atherosclerotic plaques of the carotid sinus at the late stages of atherosclerosis development. Russian Physiological Journal named after I. M. Sechenov. 2022; 108(5): 649–66. https://doi.org/10.31857/S0869813922050041Погосова Н. В., Юферева Ю. М., Качанова Н. П., Метельская В. А., Колтунов И. Е., Воронина В. П., и др. Разработка алгоритма диагностики доклинического атеросклероза у пациентов из группы высокого риска развития сердечно-сосудистых заболеваний. Кардиология. 2020;60(2):75–82. https://doi.org/10.18087/cardio.2020.2.n964Pogosova N. V., YuferevaYu. M., Kachanova N. P., Metelskaya V. A., Koltunov I. E., Voronina V. P., etal. Development of an algorithm for diagnosing preclinical atherosclerosis in high-risk patients development of cardiovascular diseases. Cardiology. 2020; 60(2): 75–82. https://doi.org/10.18087/cardio.2020.2.n964Олейников В. Э., Салямова Л. И., Хромова А. А., Куприянова С. Н., Квасова О. Г., Илясов И. Б. Прогнозирование коронарного атеросклероза у пациентов с ишемической болезнью сердца молодого возраста с использованием неинвазивного биомаркера. Российский кардиологический журнал. 2020;25(12):3924. https://doi.org/10.15829/1560–4071–2020–3924Oleynikov V. E., Salyamova L. I., Khromova A. A., Kupriyanova S. N., Kvasova O. G., Ilyasov I. B. Prediction of coronary atherosclerosis in young patients with coronary heart disease using a non-invasive biomarker. Russian Journal of Cardiology. 2020; 25(12): 3924. https://doi.org/10.15829/1560–4071–2020–3924Kukharchuk V. V., Ezhov M. V., Sergienko I. V., Arabidze G. G., Balakhonova T. V., Gurevich V. S., идр. Eurasian association of cardiology (EAC)/ russian national atherosclerosis society (RNAS, russia) guidelines for the diagnosis and correction of dyslipidemia for the prevention and treatment of atherosclerosis (2020). Evrazijskij kardiologičeskij žurnal. 2020;(2):6–29. https://doi.org/10.38109/2225–1685–2020–2–6–29Kukharchuk V. V., Ezhov M. V., Sergienko I. V., Arabidze G. G., Balakhonova T. V., Gurevich V. S., идр. Eurasian association of cardiology (EAC)/ russian national atherosclerosis society (RNAS, russia) guidelines for the diagnosis and correction of dyslipidemia for the prevention and treatment of atherosclerosis (2020). Evrazijskij kardiologičeskij žurnal. 2020;(2):6–29. https://doi.org/10.38109/2225–1685–2020–2–6–29Abdulsalam M., Feng J. The composition of vulnerable plaque and its effect on arterial waveforms. Journal of the Mechanical Behavior of Biomedical Materials. 2021;119:104491. https://doi.org/10.1016/j.jmbbm.2021.104491Abdulsalam M., Feng J. The composition of vulnerable plaque and its effect on arterial waveforms. Journal of the Mechanical Behavior of Biomedical Materials. 2021;119:104491. https://doi.org/10.1016/j.jmbbm.2021.104491Biscetti F., Tinelli G., Rando M. M., Nardella E., Cecchini A. L., Angelini F., идр. Correction to: Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population. CardiovascDiabetol. 2021;20:184. https://doi.org/10.1186/s12933–021–01376–6Biscetti F., Tinelli G., Rando M. M., Nardella E., Cecchini A. L., Angelini F., идр. Correction to: Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population. CardiovascDiabetol. 2021;20:184. https://doi.org/10.1186/s12933–021–01376–6Пигаревский П. В., Снегова В. А., Назаров П. Г. Макрофаги и их роль в дестабилизации атеросклеротической бляшки. Кардиология. 2019;59(4):88–91. https://doi.org/10.18087/cardio.2019.4.10254Pigarevsky P. V., Snegova V. A., Nazarov P. G. Macrophages and their role in the destabilization of atherosclerotic plaque. Cardiology. 2019;59(4):88–91. https://doi.org/10.18087/cardio.2019.4.10254Fadini G. P., Simoni F., Cappellari R., Vitturi N., Galasso S., Kreutzenberg S. V., идр. Pro-inflammatory monocyte-macrophage polarization imbalance in human hypercholesterolemia and atherosclerosis. Atherosclerosis. 2014;237(2):805–8. https://doi.org/10.1016/j.atherosclerosis.2014.10.106Fadini G. P., Simoni F., Cappellari R., Vitturi N., Galasso S., Kreutzenberg S. V., идр. Pro-inflammatory monocyte-macrophage polarization imbalance in human hypercholesterolemia and atherosclerosis. Atherosclerosis. 2014;237(2):805–8. https://doi.org/10.1016/j.atherosclerosis.2014.10.106Isali I., McClellan P., R. Wong T., Cingireddi S., Jain M., M. Anderson J., Hijaz A., Akkus O. In Vivo Delivery of M0, M1, and M2 Macrophage Subtypes via Genipin-Cross-Linked Collagen Biotextile. Tissue Engineering. 2022; Part A: 672–684. http://doi.org/10.1089/ten.tea.2021.0203Isali I., McClellan P., R. Wong T., Cingireddi S., Jain M., M. Anderson J., Hijaz A., Akkus O. In Vivo Delivery of M0, M1, and M2 Macrophage Subtypes via Genipin-Cross-Linked Collagen Biotextile. Tissue Engineering. 2022; Part A: 672–684. http://doi.org/10.1089/ten.tea.2021.0203Devaraj S., Jialal I. CRP Polarizes Human Macrophages to a M1 Phenotype and Inhibits Transformation to the M2 Phenotype. Arterioscler Thromb Vasc Biol. 2011;31(6):1397–402. https://doi.org/10.1161/ATVBAHA.111.225508Devaraj S., Jialal I. CRP Polarizes Human Macrophages to a M1 Phenotype and Inhibits Transformation to the M2 Phenotype. Arterioscler Thromb Vasc Biol. 2011;31(6):1397–402. https://doi.org/10.1161/ATVBAHA.111.225508Piekarska A., Pérès M., Toton M., Kulczycka M., Lewandowski K., Vergez F. Identification of circulating regulatory T lymphocytes with membrane markers – a new multiparameter flow cytometry protocol. Folia Histochemica et Cytobiologica. 2021;59(2):75–85. https://doi.org/10.5603/FHC.a2021.0014Piekarska A., Pérès M., Toton M., Kulczycka M., Lewandowski K., Vergez F. Identification of circulating regulatory T lymphocytes with membrane markers – a new multiparameter flow cytometry protocol. Folia Histochemica et Cytobiologica. 2021;59(2):75–85. https://doi.org/10.5603/FHC.a2021.0014Emini Veseli B., Perrotta P., De Meyer, Roth L., Van der Donckt C, Martinet W., идр. Animal models of atherosclerosis. European Journal of Pharmacology. 2017;816:3–13. https://doi.org/10.1016/j.ejphar.2017.05.010Emini Veseli B., Perrotta P., De Meyer, Roth L., Van der Donckt C, Martinet W., идр. Animal models of atherosclerosis. European Journal of Pharmacology. 2017;816:3–13. https://doi.org/10.1016/j.ejphar.2017.05.010Skogsberg J., Lundström J., Kovacs A., Nilsson R., Noori P., Maleki S., идр. Transcriptional Profiling Uncovers a Network of Cholesterol-Responsive Atherosclerosis Target Genes. PLoS Genet. 2008;4(3): e1000036. https://doi.org/10.1371/journal.pgen.1000036Skogsberg J., Lundström J., Kovacs A., Nilsson R., Noori P., Maleki S., идр. Transcriptional Profiling Uncovers a Network of Cholesterol-Responsive Atherosclerosis Target Genes. PLoS Genet. 2008;4(3): e1000036. https://doi.org/10.1371/journal.pgen.1000036Wang J., Kang Z., Liu Y., Li Z., Liu Y., Liu J. Identification of immune cell infiltration and diagnostic biomarkers in unstable atherosclerotic plaques by integrated bioinformatics analysis and machine learning. Front Immunol. 2022;13:956078. https://doi.org/10.3389/fimmu.2022.956078Wang J., Kang Z., Liu Y., Li Z., Liu Y., Liu J. Identification of immune cell infiltration and diagnostic biomarkers in unstable atherosclerotic plaques by integrated bioinformatics analysis and machine learning. Front Immunol. 2022;13:956078. https://doi.org/10.3389/fimmu.2022.956078Bardina M., Pawelzikc S. C., Lagrangea J., Mahdic A., Arnardottirc H., Regnaulta V., Feved B., Lacolleya P., Michela J. B., Merciera N., Back M. The resolvin D 2 – GPR 18 axis is expressed in human coronary atherosclerosis and transduces atheroprotection in apolipoprotein E deficient mice – ScienceDirect. https://doi.org/10.1016/j.bcp.2022.115075Bardina M., Pawelzikc S. C., Lagrangea J., Mahdic A., Arnardottirc H., Regnaulta V., Feved B., Lacolleya P., Michela J. B., Merciera N., Back M. The resolvin D 2 – GPR 18 axis is expressed in human coronary atherosclerosis and transduces atheroprotection in apolipoprotein E deficient mice – ScienceDirect. https://doi.org/10.1016/j.bcp.2022.115075Petri M. H., Laguna-Fernández A., Gonzalez-Diez M., Paulsson-Berne G., Hansson G. K., Bäck M. The role of the FPR 2/ALX receptor in atherosclerosis development and plaque stability. Cardiovasc Res. 2015;105(1):65–74. https://doi.org/10.1093/cvr/cvu224Petri M. H., Laguna-Fernández A., Gonzalez-Diez M., Paulsson-Berne G., Hansson G. K., Bäck M. The role of the FPR 2/ALX receptor in atherosclerosis development and plaque stability. Cardiovasc Res. 2015;105(1):65–74. https://doi.org/10.1093/cvr/cvu224Arnold K. A., Blair J. E., Paul J. D., Shah A. P., Nathan S., Alenghat F. J. Monocyte and Macrophage Subtypes as Paired Cell Biomarkers for Coronary Artery Disease. Exp Physiol. 2019;104(9):1343–52. https://doi.org/10.1113/EP087827Arnold K. A., Blair J. E., Paul J. D., Shah A. P., Nathan S., Alenghat F. J. Monocyte and Macrophage Subtypes as Paired Cell Biomarkers for Coronary Artery Disease. Exp Physiol. 2019;104(9):1343–52. https://doi.org/10.1113/EP087827Williams H, Cassorla G, Pertsoulis N, Patel V, Vicaretti M, Marmash N, et al. Human classical monocytes display unbalanced M1/M2 phenotype with increased atherosclerotic risk and presence of disease – International Angiology 2017;36(2):145–55. https://doi.org/10.23736/S0392–9590.16.03661–0Williams H, Cassorla G, Pertsoulis N, Patel V, Vicaretti M, Marmash N, et al. Human classical monocytes display unbalanced M1/M2 phenotype with increased atherosclerotic risk and presence of disease – International Angiology 2017;36(2):145–55. https://doi.org/10.23736/S0392–9590.16.03661–0Ridker P. M. From CRP to IL-6 to IL-1: Moving Upstream To Identify Novel Targets for Atheroprotection. Circ Res. 2016;118(1):145–56. https://doi.org/10.1161/CIRCRESAHA.115.306656Ridker P. M. From CRP to IL-6 to IL-1: Moving Upstream To Identify Novel Targets for Atheroprotection. Circ Res. 2016;118(1):145–56. https://doi.org/10.1161/CIRCRESAHA.115.306656Уткина Е. А., Афанасьева О. И., Покровский С. Н. С-реактивный белок: патогенетические свойства и возможная терапевтическая мишень. Российский кардиологический журнал. 2021;26(6):4138. https://doi.org/10.15829/1560–4071–2021–4138Utkina E. A., Afanasyeva O. I., Pokrovsky S. N. C-reactive protein: pathogenetic properties and a possible therapeutic target. Russian Journal of Cardiology. 2021;26(6):4138. https://doi.org/10.15829/1560–4071–2021–4138Vlad M. L., Manea S. A., Lazar A. G., RaicuM., MuresianH., SimionescuM., идр. Histone Acetyltransferase-Dependent Pathways Mediate Upregulation of NADPH Oxidase 5 in Human Macrophages under Inflammatory Conditions: A Potential Mechanism of Reactive Oxygen Species Overproduction in Atherosclerosis. Oxid Med Cell Longev. 2019; 3201062. https://doi.org/10.1155/2019/3201062Vlad M. L., Manea S. A., Lazar A. G., RaicuM., MuresianH., SimionescuM., идр. Histone Acetyltransferase-Dependent Pathways Mediate Upregulation of NADPH Oxidase 5 in Human Macrophages under Inflammatory Conditions: A Potential Mechanism of Reactive Oxygen Species Overproduction in Atherosclerosis. Oxid Med Cell Longev. 2019; 3201062. https://doi.org/10.1155/2019/3201062Chen L., Huan X., Gao X. D., Yu W. H., Xiao G. H., Li T. F., идр. Biological Functions of the DNA Glycosylase NEIL3 and Its Role in Disease Progression Including Cancer. Cancers (Basel). 2022;14(23):5722. https://doi.org/10.3390/cancers14235722Chen L., Huan X., Gao X. D., Yu W. H., Xiao G. H., Li T. F., идр. Biological Functions of the DNA Glycosylase NEIL3 and Its Role in Disease Progression Including Cancer. Cancers (Basel). 2022;14(23):5722. https://doi.org/10.3390/cancers14235722Liu M., Doublié S., Wallace S. S. Neil3, the final frontier for the DNA glycosylases that recognize oxidative damage. Mutat Res. 2013:4–11. https://doi.org/10.1016/j.mrf-mmm. 2012. 12. 003Liu M., Doublié S., Wallace S. S. Neil3, the final frontier for the DNA glycosylases that recognize oxidative damage. Mutat Res. 2013:4–11. https://doi.org/10.1016/j.mrf-mmm.2012.12.003Skarpengland T., Holm S., Scheffler K., Gregersen I., Dahl T. B., Suganthan R., идр. Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice. SciRep. 2016;6:28337. https://doi.org/10.1038/srep28337Skarpengland T., Holm S., Scheffler K., Gregersen I., Dahl T. B., Suganthan R., идр. Neil3-dependent base excision repair regulates lipid metabolism and prevents atherosclerosis in Apoe-deficient mice. SciRep. 2016;6:28337. https://doi.org/10.1038/srep28337Котляров С. Н., Котлярова А. А. Участие ABC-транспортеров в липидном обмене и патогенезе атеросклероза. Геныиклетки. 2020;15(3):22–8. https://doi.org/10.23868/202011003Kotlyarov S. N., Kotlyarova A. A. Participation of ABC transporters in lipid metabolism and the pathogenesis of atherosclerosis. Genes and cells. 2020; 15(3): 22–8. https://doi.org/10.23868/202011003Павлович С. Л. АТФ-связывающиетранспортныебелкисемейства abc (ATP-binding cassette transporters, abc). Номенклатура, структура, молекулярное разнообразие, функция, участие в функционировании системы биотрансформации ксенобиотиков. Труды Карельского научного центра Российской академии наук. 2020;(3):5–19. http://dx.doi.org/10.17076/eb1044Pavlovich S. L. ATP-binding cassette transporters (ATP-binding cassette transporters, abc) family proteins. Nomenclature, structure, molecular diversity, function, participation in the functioning of the xenobiotic biotransformation system. Proceedings of the Karelian Scientific Center of the Russian Academy of Sciences. 2020; (3): 5–19. http://dx.doi.org/10.17076/eb1044Peters L. J. F., Biessen E. A. L., Hohl M., Weber C., van der Vorst E. P. C., Santovito D. Small Things Matter: Relevance of MicroRNAs in Cardiovascular Disease. Front Physiol. 2020;11:793. https://doi.org/10.3389/fphys.2020.00793Peters L. J. F., Biessen E. A. L., Hohl M., Weber C., van der Vorst E. P. C., Santovito D. Small Things Matter: Relevance of MicroRNAs in Cardiovascular Disease. Front Physiol. 2020;11:793. https://doi.org/10.3389/fphys.2020.00793He S, Wu C, Xiao J, Li D, Sun Z, Li M. Endothelial extracellular vesiclesmodulate the macrophage phenotype: Potentialimplications in atherosclerosis. Scand J Immunol. 2018; 87: e12648. https://doi.org/10.1111/sji.1264816.He S, Wu C, Xiao J, Li D, Sun Z, Li M. Endothelial extracellular vesiclesmodulate the macrophage phenotype: Potentialimplications in atherosclerosis. Scand J Immunol. 2018; 87: e12648. https://doi.org/10.1111/sji.1264816.Panda A. C. Circular RNAs Act as miRNA Sponges. Circular RNAs: Biogenesis and Functions. Singapore: Springer. 2018: 67–79. https://doi.org/10.1007/978–981–13–1426–1_6Panda A. C. Circular RNAs Act as miRNA Sponges. Circular RNAs: Biogenesis and Functions. Singapore: Springer. 2018: 67–79. https://doi.org/10.1007/978–981–13–1426–1_6Alkan A. H., Akgül B. Endogenous miRNA Sponges. miRNomics: MicroRNA Biology and Computational Analysis. New York, NY: Springer US. 2022; 91–104. https://doi.org/10.1007/978–1–0716–1170–8_5Alkan A. H., Akgül B. Endogenous miRNA Sponges. miRNomics: MicroRNA Biology and Computational Analysis. New York, NY: Springer US. 2022; 91–104. https://doi.org/10.1007/978–1–0716–1170–8_5Montalto F. I., De Amicis F. Cyclin D 1 in Cancer: A Molecular Connection for Cell Cycle Control, Adhesion and Invasion in Tumor and Stroma. Cells 9. 2020;9(12):2648. https://doi.org/10.3390/cells9122648Montalto F. I., De Amicis F. Cyclin D 1 in Cancer: A Molecular Connection for Cell Cycle Control, Adhesion and Invasion in Tumor and Stroma. Cells 9. 2020;9(12):2648. https://doi.org/10.3390/cells9122648Yang L., Yang F., Zhao H., Wang M., Zhang Y. Circular RNA circCHFR Facilitates the Proliferation and Migration of Vascular Smooth Muscle via miR-370/FOXO1/Cyclin D 1 Pathway. Mol Ther Nucleic Acids. 2019;16:434–41. https://doi.org/10.1016/j.omtn.2019.02.028Yang L., Yang F., Zhao H., Wang M., Zhang Y. Circular RNA circCHFR Facilitates the Proliferation and Migration of Vascular Smooth Muscle via miR-370/FOXO1/Cyclin D 1 Pathway. Mol Ther Nucleic Acids. 2019;16:434–41. https://doi.org/10.1016/j.omtn.2019.02.028Yu H., Zhao L., Zhao Y., Fei J., Zhang W. Circular RNA circ_0029589 regulates proliferation, migration, invasion, and apoptosis in ox-LDL-stimulated VSMCs by regulating miR-424–5p/IGF2 axis. Vascular Pharmacology. 2020;135:106782. https://doi.org/10.1016/j.vph.2020.106782Yu H., Zhao L., Zhao Y., Fei J., Zhang W. Circular RNA circ_0029589 regulates proliferation, migration, invasion, and apoptosis in ox-LDL-stimulated VSMCs by regulating miR-424–5p/IGF2 axis. Vascular Pharmacology. 2020;135:106782. https://doi.org/10.1016/j.vph.2020.106782Guo D., Zhao Y., Wang N., You N., Zhu W., Zhang P., идр. GADD 45g acts as a novel tumor suppressor, and its activation suggests new combination regimens for the treatment of AML. Blood. 2021;138(6):464–79. https://doi.org/10.1182/blood.2020008229Guo D., Zhao Y., Wang N., You N., Zhu W., Zhang P., идр. GADD 45g acts as a novel tumor suppressor, and its activation suggests new combination regimens for the treatment of AML. Blood. 2021;138(6):464–79. https://doi.org/10.1182/blood.2020008229Li Y., Wang B. Circular RNA circCHFR downregulation protects against oxidized low-density lipoprotein-induced endothelial injury via regulation of microRNA-15b-5p/ growth arrest and DNA damage inducible gamma. Bioengineered. 2022; 13(2):4481–92. https://doi.org/10.1080/21655979.2022.2032967Li Y., Wang B. Circular RNA circCHFR downregulation protects against oxidized low-density lipoprotein-induced endothelial injury via regulation of microRNA-15b-5p/ growth arrest and DNA damage inducible gamma. Bioengineered. 2022; 13(2):4481–92. https://doi.org/10.1080/21655979.2022.2032967

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