Annals of Clinical and Experimental NeurologyAnnals of Clinical and Experimental Neurology2075-54732409-2533Research Center of Neurology93310.54101/ACEN.2023.1.8Research ArticleMicroRNA detection in carotid atherosclerosis: prospects for clinical useTanashyanМarine М.<p>D. Sci. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences, Deputy Director for Research, Head, 1<sup>st</sup> Neurological Department, Research Center of Neurology</p>mtanashyan@neurology.ruhttps://orcid.org/0000-0002-5883-8119RakurazhevAnton A.<p>Cand. Sci. (Med.), Neurologist, Senior Researcher, 1<sup>st </sup>Neurological Department, Research Center of Neurology</p>rasckey@live.comhttps://orcid.org/0000-0003-0522-767XKuznetsovaPolina I.<p>Cand. Sci. (Med.), Neurologist, Researcher, 1<sup>st</sup> Neurological Department, Research Center of Neurology</p>angioneurology0@gmail.comhttps://orcid.org/0000-0002-4626-6520MazurAndrew S.<p>Postgraduate Student, 1<sup>st</sup> Neurological Department, Research Center of Neurology</p>a1699466@yandex.ruhttps://orcid.org/0000-0001-8960-721XShabalinaАlla A.<p>D. Sci. (Med.), Leading Researcher, Head, Laboratory of Hemorheology, Hemostasis and Pharmacokinetics (with Clinical Laboratory Diagnostics), Research Center of Neurology</p>ashabalina@yandex.ruhttps://orcid.org/0000-0001-9604-7775Research Center of Neurology2903202317169741701202320012023Copyright © 2023, Tanashyan М.М., Rakurazhev A.A., Kuznetsova P.I., Mazur A.S., Shabalina А.A.2023<p>Carotid atherosclerosis is a significant cause of cerebrovascular disease. However, with many candidate markers, precise assessment of its development and progression risks is still limited. This paper reviews state-of-the-art concepts of microRNA as an atherogenesis biomarker throughout various stages including endothelial dysfunction, cholesterol/lipid metabolism, inflammation, oxidative stress, angiogenesis regulation, and proliferation and migration of vascular smooth muscle cells. Based on the available literature, we have described most significant microRNAs for each stage characterized in brief. We have visualized interactions between microRNAs and validated target genes with MIENTURNET and suggest and justify a set of microRNAs for further pilot studies of carotid atherosclerosis.</p>microRNAatherosclerosisatherogenesiscerebrovascular diseasebiomarkersмикроРНКатеросклерозатерогенезцереброваскулярная патологиябиомаркеры[Mettananda K.C.D., Eshani M.D.P., Wettasinghe L.M. et al. Prevalence and correlates of carotid artery stenosis in a cohort of Sri Lankan ischaemic stroke patients. BMC Neurol. 2021; 21: 385. doi: 10.1186/s12883-021-02415-1][Song P., Fang Z., Wang H. et al. Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: a systematic review, meta-analysis, and modelling study. Lancet Glob. Health. 2020; 8(5): e721–e729. doi: 10.1016/S2214-109X(20)30117-0][Танашян М.М., Лагода О.В., Раскуражев А.А. и др. Экстра- versus интракраниальный атеросклероз: две грани одной проблемы. Российский неврологический журнал. 2022; 27(3): 11–19. Tanashyan M.M., Lagoda O.V., Raskurazhev A.A. et al. Extra- versus intracranial atherosclerosis: two facets of the same problem. Russian Neurological Journal. 2022; 27(3): 11–19. (In Russ.) doi: 10.30629/2658-7947-2022-27-3-11-19][Раскуражев А.А., Танашян М.М. Роль микроРНК в цереброваскулярной патологии. Анналы клинической и экспериментальной неврологии. 2019; 13(3): 41–46. Raskurazhev A.A., Tanashyan M.M. The role of micro-RNA in cerebrovascular disease. Annals of Clinical and Experimental Neurology. 2019; 13(3): 41–46. (In Russ.) doi: 10.25692/ACEN.2019.3.6][Кучер А.Н., Назаренко М.С. Роль микро-РНК при атерогенезе. Кардиология. 2017; 57(9): 65–76. Kucher A.N., Nazarenko M.S. The role of microRNA in atherogenesis. Cardiology. 2017; 57(9): 65–76. (In Russ.) doi: 10.18087/cardio.2017.9.10022][Badacz R., Przewłocki T., Legutko J. et al. microRNAs associated with carotid plaque development and vulnerability: the clinician’s perspective. Int. J. Mol. Sci. 2022; 23(24): 15645. doi: 10.3390/ijms232415645][Раскуражев А.А., Шабалина А.А., Кузнецова П.И., Танашян М.М. МикроРНК как значимые биомаркеры атеросклеротической цереброваскулярной патологии. Анналы клинической и экспериментальной неврологии. 2022; 16(1): 5–13. Raskurazhev A.A., Shabalina A.A., Kuznetsova P.I., Tanashyan M.M. Micro- RNA as significant biomarkers of cerebrovascular atherosclerosis. Annals of Clinical and Experimental Neurology. 2022; 16(1): 5–13. (In Russ.) doi: 10.54101/ACEN.2022.1.1][Raskurazhev A.A., Kuznetsova P.I., Shabalina A.A., Tanashyan M.M. MicroRNA and hemostasis profile of carotid atherosclerosis. Int. J. Mol. Sci. 2022: 23: 10974. doi: 10.3390/ijms231810974][Licursi V., Conte F., Fiscon G., Paci P. MIENTURNET: an interactive web tool for microRNA-target enrichment and network-based analysis. BMC Bioinformatics. 2019; 20(1): 545. doi: 10.1186/s12859-019-3105-x][Widlansky M.E., Gokce N., Keaney J.F. Jr, Vita J.A. The clinical implications of endothelial dysfunction. J. Am. Coll. Cardiol. 2003; 42(7): 1149–1160. doi: 10.1016/s0735-1097(03)00994-x][Deng X., Chu X., Wang P. et al. MicroRNA-29a-3p reduces TNFα-induced endothelial dysfunction by targeting tumor necrosis factor receptor 1. Mol. Ther. Nucleic Acids. 2019; 18: 903–915. doi: 10.1016/j.omtn.2019.10.014][Zhang Y, Wang L, Xu J, et al. Up-regulated miR-106b inhibits ox-LDL-induced endothelial cell apoptosis in atherosclerosis. Braz. J. Med. Biol. Res. 2020; 53(3): e8960. doi: 10.1590/1414-431X20198960][Cheng H.S., Sivachandran N., Lau A. et al. MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways. EMBO Mol. Med. 2013; 5(7): 1017–1034. doi: 10.1002/emmm.201202318][Wang C., Liu C., Shi J. et al. Nicotine exacerbates endothelial dysfunction and drives atherosclerosis via extracellular vesicle-miRNA. Cardiovasc. Res. 2022; 25:cvac140. doi: 10.1093/cvr/cvac140][Kuo H.M., Lin C.Y., Lam H.C. et al. PTEN overexpression attenuates angiogenic processes of endothelial cells by blockade of endothelin-1/endothelin B receptor signaling. Atherosclerosis. 2012; 221(2): 341–349. doi: 10.1016/j.atherosclerosis.2010.08.067][Moulton K.S., Li M., Strand K. et al. PTEN deficiency promotes pathological vascular remodeling of human coronary arteries. JCI Insight. 2018; 3(4): e97228. doi: 10.1172/jci.insight.97228][Gao Y., Li G., Fan S. et al. Circ_0093887 upregulates CCND2 and SUCNR1 to inhibit the ox-LDL-induced endothelial dysfunction in atherosclerosis by functioning as a miR-876-3p sponge. Clin. Exp. Pharmacol. Physiol. 2021; 48(8): 1137–1149. doi: 10.1111/1440-1681.13504][Feng J., Li A., Deng J. et al. miR-21 attenuates lipopolysaccharide-induced lipid accumulation and inflammatory response: potential role in cerebrovascular disease. Lipids Health Dis. 2014; 13: 27. doi: 10.1186/1476-511X-13-27][Price N.L., Rotllan N., Canfrán-Duque A. et al. Genetic dissection of the impact of miR-33a and miR-33b during the progression of atherosclerosis. Cell Rep. 2017; 21(5): 1317–1330. doi: 10.1016/j.celrep.2017.10.023][Tang X.E., Li H., Chen L.Y. et al. IL-8 negatively regulates ABCA1 expression and cholesterol efflux via upregulating miR-183 in THP-1 macrophage-derived foam cells. Cytokine. 2019; 122: 154385. doi: 10.1016/j.cyto.2018.04.028][Fan M., Huang Y., Li K. et al. ox-LDL regulates proliferation and apoptosis in VSMCs by controlling the miR-183-5p/FOXO1. Genes Genomics. 2022; 44(6): 671–681. doi: 10.1007/s13258-022-01236-x][Rafiei A., Ferns G.A., Ahmadi R. et al. Expression levels of miR-27a, miR-329, ABCA1, and ABCG1 genes in peripheral blood mononuclear cells and their correlation with serum levels of oxidative stress and hs-CRP in the patients with coronary artery disease. IUBMB Life. 2021; 73(1): 223–237. doi: 10.1002/iub.2421][Li J., Li K., Chen X. Inflammation-regulatory microRNAs: Valuable targets for intracranial atherosclerosis. J. Neurosci. Res. 2019; 97(10): 1242–1252. doi: 10.1002/jnr.24487][Pankratz F., Hohnloser C., Bemtgen X. et al. MicroRNA-100 suppresses chronic vascular inflammation by stimulation of endothelial autophagy. Circ. Res. 2018; 122(3): 417–432. doi: 10.1161/CIRCRESAHA.117.311428][Yang K., He Y.S., Wang X.Q. et al. MiR-146a inhibits oxidized low-density lipoprotein-induced lipid accumulation and inflammatory response via targeting toll-like receptor 4. FEBS Lett. 2011; 585(6): 854–860. doi: 10.1016/j.febslet.2011.02.009][Döring Y., Noels H., van der Vorst E.P.C. et al. Vascular CXCR4 limits atherosclerosis by maintaining arterial integrity: evidence from mouse and human studies. Circulation. 2017; 136(4): 388–403. doi: 10.1161/CIRCULATIONAHA.117.027646][Magenta A., Greco S., Gaetano C., Martelli F. Oxidative stress and microRNAs in vascular diseases. Int. J. Mol. Sci. 2013; 14(9): 17319–17346. doi: 10.3390/ijms140917319][Yang S., Mi X., Chen Y. et al. MicroRNA-216a induces endothelial senescence and inflammation via Smad3/IκBα pathway. J. Cell Mol. Med. 2018; 22(5): 2739–2749. doi: 10.1111/jcmm.13567][Yang S., Chen Y., Mi X. et al. MicroRNA-216a promotes endothelial inflammation by smad7/IκBα pathway in atherosclerosis. Dis. Markers. 2020; 2020: 8864322. doi: 10.1155/2020/8864322][van Ingen E., Foks A.C., Woudenberg T. et al. Inhibition of micro- RNA-494-3p activates Wnt signaling and reduces proinflammatory macrophage polarization in atherosclerosis. Mol. Ther. Nucleic Acids. 2021; 26: 1228–1239. doi: 10.1016/j.omtn.2021.10.027][Zhu L., Wang Y., Qiao F. microRNA-223 and microRNA-126 are clinical indicators for predicting the plaque stability in carotid atherosclerosis patients. J. Hum. Hypertens. 2022. doi: 10.1038/s41371-022-00760-3][Chen L., Zheng S.Y., Yang C.Q. et al. MiR-155-5p inhibits the proliferation and migration of VSMCs and HUVECs in atherosclerosis by targeting AKT1. Eur. Rev. Med. Pharmacol. Sci. 2019; 23(5): 2223–2233. doi: 10.26355/eurrev_201903_17270][Xu W., Qian L., Yuan X., Lu Y. MicroRNA-223-3p inhibits oxidized low-density lipoprotein-mediated NLRP3 inflammasome activation via directly targeting NLRP3 and FOXO3. Clin. Hemorheol. Microcirc. 2022; 81(3): 241–253. doi: 10.3233/CH-211232][Sun B., Shan Z., Sun G., Wang X. Micro-RNA-183-5p acts as a potential diagnostic biomarker for atherosclerosis and regulates the growth of vascular smooth muscle cell. J. Chin. Med. Assoc. 2021; 84(1): 33–37. doi: 10.1097/JCMA.0000000000000433][Xu H., Cui Y., Liu X. et al. miR-1290 promotes IL-8-mediated vascular endothelial cell adhesion by targeting GSK-3β. Mol. Biol. Rep. 2022; 49(3): 1871–1882. doi: 10.1007/s11033-021-06998-3][Sun B., Cao Q., Meng M., Wang X. MicroRNA-186-5p serves as a diagnostic biomarker in atherosclerosis and regulates vascular smooth muscle cell proliferation and migration. Cell Mol. Biol. Lett. 2020; 25: 27. doi: 10.1186/s11658-020-00220-1][Shi Y., Li H., Gu J. et al. Wnt5a/Ror2 promotes vascular smooth muscle cells proliferation via activating PKC. Folia Histochem. Cytobiol. 2022; 60(3): 271–279. doi: 10.5603/FHC.a2022.0026][Wang W., Ma F., Zhang H. MicroRNA-374 is a potential diagnostic biomarker for atherosclerosis and regulates the proliferation and migration of vascular smooth muscle cells. Cardiovasc. Diagn. Ther. 2020; 10(4): 687–694. doi: 10.21037/cdt-20-444][Sun H., Wu S., Sun B. MicroRNA-532-5p protects against atherosclerosis through inhibiting vascular smooth muscle cell proliferation and migration. Cardiovasc. Diagn. Ther. 2020; 10(3): 481–489. doi: 10.21037/cdt-20-91]