Skip to main content
Log in

miRNA Regulome in Different Atherosclerosis Phenotypes

  • REVIEWS
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

Dysregulation of microRNA (miRNA) expression is associated with a susceptibility to many diseases, including atherosclerotic lesions of the coronary and carotid arteries and the development of clinical complications such as coronary heart disease, myocardial infarction, chronic cerebral ischemia, ischemic stroke. Recently, more and more studies analyze the miRNA regulome including a network of regulatory elements for the expression of miRNAs themselves and targets under their control. The review summarizes the data from articles concerned miRNA expression and changes in DNA methylation in the miRNA genes in human atherosclerotic arteries, as well as with the analysis of the association between single nucleotide polymorphisms and copy number variations in the miRNA genes with clinical complications of atherosclerosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. Libby P., Buring J.E., Badimon L., Hansson G.K., Deanfield J., Bittencourt M.S., Tokgözoğlu L., Lewis E.F. 2019. Atherosclerosis. Nat. Rev. Dis. Primers. 5 (1), 56. https://doi.org/10.1038/s41572-019-0106-z

    Article  PubMed  Google Scholar 

  2. Basatemur G.L., Jørgensen H.F., Clarke M., Bennett M.R., Mallat Z. 2019. Vascular smooth muscle cells in atherosclerosis. Nat. Rev. Cardiol. 16 (12), 727–744. https://doi.org/10.1038/s41569-019-0227-9

    Article  PubMed  Google Scholar 

  3. Chinetti-Gbaguidi G., Colin S., Staels B. 2015. Macrophage subsets in atherosclerosis. Nat. Rev. Cardiol. 12 (1), 10–17. https://doi.org/10.1038/nrcardio.2014.173

    Article  CAS  PubMed  Google Scholar 

  4. Raitoharju E., Oksala N., Lehtimäki T. 2013. MicroRNAs in the atherosclerotic plaque. Clin. Chem. 59 (12), 1708–1721. https://doi.org/10.1373/clinchem.2013.204917

    Article  CAS  PubMed  Google Scholar 

  5. Andreou I., Sun X., Stone P.H., Edelman E.R., Feinberg M.W. 2015. miRNAs in atherosclerotic plaque initiation, progression, and rupture. Trends. Mol. Med. 21 (5), 307–318. https://doi.org/10.1016/j.molmed.2015.02.003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Feinberg M.W., Moore K.J. 2016. MicroRNA regulation of atherosclerosis. Circ. Res. 118(4), 703–720. https://doi.org/10.1161/CIRCRESAHA.115.306300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kucher A.N., Nazarenko M.S. 2017. Role of microRNA in atherogenesis. Kardiologiya. 57 (9), 65–76.

    Article  CAS  PubMed  Google Scholar 

  8. Fasolo F., Di Gregoli K., Maegdefessel L., Johnson J.L. 2019. Non-coding RNAs in cardiovascular cell biology and atherosclerosis. Cardiovasc. Res. 115 (12), 1732–1756. https://doi.org/10.1093/cvr/cvz203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Friedman R.C., Farh K.K.-H., Burge C.B., Bartel D.P. 2009. Most mammalian mRNAs are conserved targets of microRNAs. Genome Res. 19 (1), 92–105. https://doi.org/10.1101/gr.082701.108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Catalanotto C., Cogoni C., Zardo G. 2016. MicroRNA in control of gene expression: An overview of nuclear functions. Int. J. Mol. Sci. 17 (10), 1712. https://doi.org/10.3390/ijms17101712

    Article  CAS  PubMed Central  Google Scholar 

  11. Lu Y., Thavarajah T., Gu W., Cai J., Xu Q. 2018. Impact of miRNA in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 38 (9), e159–e170. https://doi.org/10.1161/ATVBAHA.118.310227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kozomara A., Birgaoanu M., Griffiths-Jones S. 2019. miRBase: From microRNA sequences to function. Nucleic Acids Res. 47 (D1), D155–D162. https://doi.org/10.1093/nar/gky1141

    Article  CAS  PubMed  Google Scholar 

  13. Laffont B., Rayner K.J. 2017. MicroRNAs in the pathobiology and therapy of atherosclerosis. Can. J. Cardiol. 33 (3), 313–324. https://doi.org/10.1016/j.cjca.2017.01.001

    Article  PubMed  Google Scholar 

  14. Olena A.F., Patton J.G. 2010. Genomic organization of microRNAs. J. Cell. Physiol. 222 (3), 540–545. https://doi.org/10.1002/jcp.21993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Morales S., Monzo M., Navarro A. 2017. Epigenetic regulation mechanisms of microRNA expression. Biomol. Concepts. 8 (5–6), 203–212. https://doi.org/10.1515/bmc-2017-0024

    Article  CAS  PubMed  Google Scholar 

  16. Marsico A., Huska M.R., Lasserre J., Hu H., Vucicevic D., Musahl A., Orom U., Vingron M. 2013. PROmiRNA: A new miRNA promoter recognition method uncovers the complex regulation of intronic miRNAs. Genome Biol. 14 (8), R84. https://doi.org/10.1186/gb-2013-14-8-r84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chakraborty C., Das S. 2016. Profiling cell-free and circulating miRNA: A clinical diagnostic tool for different cancers. Tumour Biol. 37 (5), 5705–5714. https://doi.org/10.1007/s13277-016-4907-3

    Article  CAS  PubMed  Google Scholar 

  18. Wong L.L., Wang J., Liew O.W., Richards A.M., Chen Y.T. 2016. MicroRNA and heart failure. Int. J. Mol. Sci. 17 (4), 502. https://doi.org/10.3390/ijms17040502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Hinske L.C., França G.S., Torres H.A., Ohara D.T., Lopes-Ramos C.M., Heyn J., Reis L.F., Ohno-Machado L., Kreth S., Galante P.A. 2014. miRIAD-integrating microRNA inter- and intragenic data. Database (Oxford). 2014, bau099. https://doi.org/10.1093/database/bau099

    Article  CAS  Google Scholar 

  20. Huang Z., Shi J., Gao Y., Cui C., Zhang S., Li J., Zhou Y., Cui Q. 2019. HMDD v3.0: A database for experimentally supported human microRNA-disease associations. Nucleic Acids Res. 47 (D1), D1013–D1017.

    Article  CAS  PubMed  Google Scholar 

  21. Sharma H., Estep M., Birerdinc A., Afendy A., Moazzez A., Elariny H., Goodman Z., Chandhoke V., Baranova A., Younossi Z.M. 2013. Expression of genes for microRNA-processing enzymes is altered in advanced non-alcoholic fatty liver disease. J. Gastroenterol. Hepatol. 28 (8), 1410–1415. https://doi.org/10.1111/jgh.12268

    Article  CAS  PubMed  Google Scholar 

  22. Cipollone F., Felicioni L., Sarzani R., Ucchino S., Spigonardo F., Mandolini C., Malatesta S., Bucci M., Mammarella C., Santovito D., de Lutiis F., Marchetti A., Mezzetti A., Buttitta F. 2011. A unique microRNA signature associated with plaque instability in humans. Stroke. 42 (9), 2556–2563. https://doi.org/10.1161/STROKEAHA.110.597575

    Article  PubMed  Google Scholar 

  23. Lovren F., Pan Y., Quan A., Singh K.K., Shukla P.C., Gupta N., Steer B.M., Ingram A.J., Gupta M., Al-Omran M., Teoh H., Marsden P.A., Verma S. 2012. MicroRNA-145 targeted therapy reduces atherosclerosis. Circulation. 126 (11, Suppl. 1), S81–S90. https://doi.org/10.1161/CIRCULATIONAHA.111.084186

    Article  CAS  PubMed  Google Scholar 

  24. Nazari-Jahantigh M., Wei Y., Noels H., Akhtar S., Zhou Z., Koenen R.R., Heyll K., Gremse F., Kiessling F., Grommes J., Weber C., Schober A. 2012. MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages. J. Clin. Invest. 122 (11), 4190–4202. https://doi.org/10.1172/JCI61716

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Santovito D., Mandolini C., Marcantonio P., De Nardis V., Bucci M., Paganelli C., Magnacca F., Ucchino S., Mastroiacovo D., Desideri G., Mezzetti A., Cipollone F. 2013. Overexpression of microRNA-145 in atherosclerotic plaques from hypertensive patients. Expert. Opin. Ther. Targets. 17 (3), 217–223. https://doi.org/10.1517/14728222.2013.745512

    Article  CAS  PubMed  Google Scholar 

  26. Di Gregoli K., Jenkins N., Salter R., White S., Newby A.C., Johnson J.L. 2014. MicroRNA-24 regulates macrophage behavior and retards atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 34 (9), 1990–2000. https://doi.org/10.1161/ATVBAHA.114.304088

    Article  CAS  PubMed  Google Scholar 

  27. Bazan H.A., Hatfield S.A., O’Malley C.B., Brooks A.J., Lightell D., Jr., Woods T.C. 2015. Acute loss of miR-221 and miR-222 in the atherosclerotic plaque shoulder accompanies plaque rupture. Stroke. 46 (11), 3285–3287. https://doi.org/10.1161/STROKEAHA.115.010567

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Cao J., Zhang K., Zheng J., Dong R. 2015. MicroRNA-146a and -21 cooperate to regulate vascular smooth muscle cell proliferation via modulation of the Notch signaling pathway. Mol. Med. Rep. 11 (4), 2889–2895. https://doi.org/10.3892/mmr.2014.3107

    Article  CAS  PubMed  Google Scholar 

  29. Maitrias P., Metzinger-Le Meuth V., Massy Z.A., M’Baya-Moutoula E., Reix T., Caus T., Metzinger L. 2015. MicroRNA deregulation in symptomatic carotid plaque. J. Vasc. Surg. 62 (5), 1245–50.e1. https://doi.org/10.1016/j.jvs.2015.06.136

    Article  PubMed  Google Scholar 

  30. Di Gregoli K., Mohamad Anuar N.N., Bianco R., White S.J., Newby A.C., George S.J., Johnson J.L. 2017. MicroRNA-181b controls atherosclerosis and aneurysms through regulation of TIMP-3 and elastin. Circ. Res. 120 (1), 49–65. https://doi.org/10.1161/CIRCRESAHA.116.309321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Bildirici A.E., Arslan S., Özbilüm Şahin N., Berkan Ö., Beton O., Yilmaz M.B. 2018. MicroRNA-221/222 expression in atherosclerotic coronary artery plaque versus internal mammarian artery and in peripheral blood samples. Biomarkers. 23 (7), 670–675. https://doi.org/10.1080/1354750X.2018.1474260

    Article  CAS  PubMed  Google Scholar 

  32. Gong F.H., Cheng W.L., Wang H., Gao M., Qin J.J., Zhang Y., Li X., Zhu X., Xia H., She Z.G. 2018. Reduced atherosclerosis lesion size, inflammatory response in miR-150 knockout mice via macrophage effects. J. Lipid Res. 59 (4), 658–669. https://doi.org/10.1194/jlr.M082651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Jin H., Li D.Y., Chernogubova E., Sun C., Busch A., Eken S.M., Saliba-Gustafsson P., Winter H., Winski G., Raaz U., Schellinger I.N., Simon N., Hegenloh R., Matic L.P., Jagodic M., et al. 2018. Local delivery of miR-21 stabilizes fibrous caps in vulnerable atherosclerotic lesions. Mol. Ther. 26 (4), 1040–1055. https://doi.org/10.1016/j.ymthe.2018.01.011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Raitoharju E., Lyytikäinen L.P., Levula M., Oksala N., Mennander A., Tarkka M., Klopp N., Illig T., Kähönen M., Karhunen P.J., Laaksonen R., Lehtimäki T. 2011. miR-21, miR-210, miR-34a, and miR-146a/b are up-regulated in human atherosclerotic plaques in the tampere vascular study. Atherosclerosis. 219 (1), 211–217. https://doi.org/10.1016/j.atherosclerosis.2011.07.020

    Article  CAS  PubMed  Google Scholar 

  35. Miller C.L., Haas U., Diaz R., Leeper N.J., Kundu R.K., Patlolla B., Assimes T.L., Kaiser F.J., Perisic L., Hedin U., Maegdefessel L., Schunkert H., Erdmann J., Quertermous T., Sczakiel G. 2014. Coronary heart disease-associated variation in TCF21 disrupts a miR-224 binding site and miRNA-mediated regulation. PLoS Genet. 10 (3), e1004263. https://doi.org/10.1371/journal.pgen.1004263

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang R., Dong L.D., Meng X.B., Shi Q., Sun W.Y. 2015. Unique microRNA signatures associated with early coronary atherosclerotic plaques. Biochem. Biophys. Res. Commun. 464 (2), 574–579. https://doi.org/10.1016/j.bbrc.2015.07.010

    Article  CAS  PubMed  Google Scholar 

  37. Xue Y., Wei Z., Ding H., Wang Q., Zhou Z., Zheng S., Zhang Y., Hou D., Liu Y., Zen K., Zhang C.Y., Li J., Wang D., Jiang X. 2015. MicroRNA-19b/221/222 induces endothelial cell dysfunction via suppression of PGC-1α in the progression of atherosclerosis. Atherosclerosis. 241 (2), 671–681. https://doi.org/10.1016/j.atherosclerosis.2015.06.031

    Article  CAS  PubMed  Google Scholar 

  38. Markus B., Grote K., Worsch M., Parviz B., Boening A., Schieffer B., Parahuleva M.S. 2016. Differential expression of microRNAs in endarterectomy specimens taken from patients with asymptomatic and symptomatic carotid plaques. PLoS One. 11 (9), e0161632. https://doi.org/10.1371/journal.pone.0161632

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Parahuleva M.S., Lipps C., Parviz B., Hölschermann H., Schieffer B., Schulz R., Euler G. 2018. MicroRNA expression profile of human advanced coronary atherosclerotic plaques. Sci. Rep. 8 (1), 7823. https://doi.org/10.1038/s41598-018-25690-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Berkan Ö., Arslan S., Lalem T., Zhang L., Şahin N.Ö., Aydemir E.I., Korkmaz Ö., Eğilmez H.R., Çekin N., Devaux Y. 2019. Regulation of microRNAs in coronary atherosclerotic plaque. Epigenomics. 11 (12), 1387–1397. https://doi.org/10.2217/epi-2019-0036

    Article  CAS  PubMed  Google Scholar 

  41. Hao L., Wang X.G., Cheng J.D., You S.Z., Ma S.H., Zhong X., Quan L., Luo B. 2014. The up-regulation of endothelin-1 and down-regulation of miRNA-125a-5p, -155, and -199a/b-3p in human atherosclerotic coronary artery. Cardiovasc. Pathol. 23 (4), 217–223. https://doi.org/10.1016/j.carpath.2014.03.009

    Article  CAS  PubMed  Google Scholar 

  42. Katano H., Nishikawa Y., Yamada H., Yamada K., Mase M. 2018. Differential expression of microRNAs in severely calcified carotid plaques. J. Stroke Cerebrovasc. Dis. 27 (1), 108–117. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.08.009

    Article  PubMed  Google Scholar 

  43. Brennan E., Wang B., McClelland A., Mohan M., Marai M., Beuscart O., Derouiche S., Gray S., Pickering R., Tikellis C., de Gaetano M., Barry M., Belton O., Ali-Shah S.T., Guiry P., et al. 2017. Protective effect of let-7 miRNA family in regulating inflammation in diabetes-associated atherosclerosis. Diabetes. 66 (8), 2266–2277. https://doi.org/10.2337/db16-1405

    Article  CAS  PubMed  Google Scholar 

  44. Kern F., Aparicio-Puerta E., Li Y., Fehlmann T., Kehl T., Wagner V., Ray K., Ludwig N., Lenhof H.P., Meese E., Keller A. 2021. miRTargetLink 2.0–interactive miRNA target gene and target pathway networks. Nucleic Acids Res. 49 (W1), W409–W416. https://doi.org/10.1093/nar/gkab297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Chang L., Zhou G., Soufan O., Xia J. 2020. miRNet 2.0: Network-based visual analytics for miRNA functional analysis and systems biology. Nucleic Acids Res. 48 (W1), W244–W251. https://doi.org/10.1093/nar/gkaa467

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kern F., Fehlmann T., Solomon J., Schwed L., Gram-mes N., Backes C., Van Keuren-Jensen K., Craig D.W., Meese E., Keller A. 2020. miEAA 2.0: Integrating multi-species microRNA enrichment analysis and workflow management systems. Nucleic Acids Res. 48 (W1), W521–W528. https://doi.org/10.1093/nar/gkaa309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Huang H.Y., Lin Y.C., Li J., Huang K.Y., Shrestha S., Hong H.C., Tang Y., Chen Y.G., Jin C.N., Yu Y., Xu J.T., Li Y.M., Cai X.X., Zhou Z.Y., Chen X.H., et al. 2020. miRTarBase 2020: Updates to the experimentally validated microRNA-target interaction database. Nucleic Acids Res. 48 (D1), D148–D154. https://doi.org/10.1093/nar/gkz896

    Article  CAS  PubMed  Google Scholar 

  48. STRING: Protein–Protein Interaction Networks Functional Enrichment Analysis. 2021. https://string-db.org/.

  49. Kanuri S.H., Ipe J., Kassab K., Gao H., Liu Y., Skaar T.C., Kreutz R.P. 2018. Next generation microRNA sequencing to identify coronary artery disease patients at risk of recurrent myocardial infarction. Atherosclerosis. 278, 232–239. https://doi.org/10.1016/j.atherosclerosis.2018.09.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Loginov V.I., Rykov S.V., Fridman M.V., Braga EA. 2015. Methylation of miRNA genes and oncogenesis. Biochemistry (Moscow). 80 (2), 145–162.

    CAS  PubMed  Google Scholar 

  51. Chhabra R. 2015. miRNA and methylation: A multifaceted liaison. Chembiochem. 16 (2), 195–203. https://doi.org/10.1002/cbic.201402449

    Article  CAS  PubMed  Google Scholar 

  52. Ma J., Hong L., Chen Z., Nie Y., Fan D. 2014. Epigenetic regulation of microRNAs in gastric cancer. Dig. Dis. Sci. 59 (4), 716–723. https://doi.org/10.1007/s10620-013-2939-8

    Article  CAS  PubMed  Google Scholar 

  53. Piletič K., Kunej T. 2016. MicroRNA epigenetic signatures in human disease. Arch. Toxicol. 90 (10), 2405–2419. https://doi.org/10.1007/s00204-016-1815-7

    Article  CAS  PubMed  Google Scholar 

  54. Kunej T., Godnic I., Ferdin J., Horvat S., Dovc P., Calin G.A. 2011. Epigenetic regulation of microRNAs in cancer: An integrated review of literature. Mutat. Res. 717 (1–2), 77–84. https://doi.org/10.1016/j.mrfmmm.2011.03.008

    Article  CAS  PubMed  Google Scholar 

  55. Baer C., Claus R., Plass C. 2013. Genome-wide epigenetic regulation of miRNAs in cancer. Cancer Res. 73 (2), 473–477. https://doi.org/10.1158/0008-5472.CAN-12-3731

    Article  CAS  PubMed  Google Scholar 

  56. Wang Z., Yao H., Lin S., Zhu X., Shen Z., Lu G., Poon W.S., Xie D., Lin M.C., Kung H.F. 2013. Transcriptional and epigenetic regulation of human microRNAs. Cancer Lett. 331 (1), 1–10. https://doi.org/10.1016/j.canlet.2012.12.006

    Article  CAS  PubMed  Google Scholar 

  57. Bell R.E., Golan T., Sheinboim D., Malcov H., Amar D., Salamon A., Liron T., Gelfman S., Gabet Y., Shamir R., Levy C. 2016. Enhancer methylation dynamics contribute to cancer plasticity and patient mortality. Genome Res. 26 (5), 601–611. https://doi.org/10.1101/gr.197194.115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Markov A.V., Nazarenko M.S., Koroleva Yu.A., Lebedev I.N., Sleptsov A.A., Frolov A.V., Popov V.A., Barbarash O.L., Barbarash L.S., Puzyrev V.P. 2014. Methylation level in the promoter region of gene HOXD4 in patients with atherosclerosis. Med. Genet. 13 (1), 39–42.

    CAS  Google Scholar 

  59. Wang Z., Guo D., Yang B., Wang J., Wang R., Wang X., Zhang Q. 2014. Integrated analysis of microarray data of atherosclerotic plaques: Modulation of the ubiquitin-proteasome system. PLoS One. 9 (10), e110288. https://doi.org/10.1371/journal.pone.0110288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Zaina S., Heyn H., Carmona F.J., Varol N., Sayols S., Condom E., Ramírez-Ruz J., Gomez A., Gonçalves I., Moran S., Esteller M. 2014. DNA methylation map of human atherosclerosis. Circ. Cardiovasc. Genet. 7 (5), 692–700. https://doi.org/10.1161/CIRCGENETICS.113.000441

    Article  CAS  PubMed  Google Scholar 

  61. Aavik E., Lumivuori H., Leppänen O., Wirth T., Häkkinen S.K., Bräsen J.H., Beschorner U., Zeller T., Braspenning M., van Criekinge W., Mäkinen K., Ylä-Herttuala S. 2015. Global DNA methylation analysis of human atherosclerotic plaques reveals extensive genomic hypomethylation and reactivation at imprinted locus 14q32 involving induction of a miRNA cluster. Eur. Heart. J. 36 (16), 993–1000. https://doi.org/10.1093/eurheartj/ehu437

    Article  CAS  PubMed  Google Scholar 

  62. Sleptcov A.A., Koroleva I.A., Frolov A.V., Popov V.A., Barbarash O.L., Puzyrev V.P. 2015. A comparison of genome-wide DNA methylation patterns between different vascular tissues from patients with coronary heart disease. PLoS One. 10 (4), e0122601. https://doi.org/10.1371/journal.pone.0122601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Ehrlich K.C., Lacey M., Ehrlich M. 2019. Tissue-specific epigenetics of atherosclerosis-related ANGPT and ANGPTL genes. Epigenomics. 11 (2), 169–186. https://doi.org/10.2217/epi-2018-0150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Nakahara M., Kobayashi N., Oka M., Nakano K., Okamura T., Yuo A., Saeki K. 2018. miR-10b deficiency affords atherosclerosis resistance. bioRxiv. 248641.

  65. Shen X., Fang J., Lv X., Pei Z., Wang Y., Jiang S., Ding K. 2011. Heparin impairs angiogenesis through inhibition of microRNA-10b. J. Biol. Chem. 286 (30), 26616–26627. https://doi.org/10.1074/jbc.M111.224212

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Wang D., Xia M., Yan X., Li D., Wang L., Xu Y., Jin T., Ling W. 2012. Gut microbiota metabolism of anthocyanin promotes reverse cholesterol transport in mice via repressing miRNA-10b. Circ. Res. 111 (8), 967–981. https://doi.org/10.1161/CIRCRESAHA.112.266502

    Article  CAS  PubMed  Google Scholar 

  67. Yu X., Li Z., Chen G., Wu W.K. 2015. MicroRNA-10b induces vascular muscle cell proliferation through Akt pathway by targeting TIP30. Curr. Vasc. Pharmacol. 13 (5), 679–686. https://doi.org/10.2174/1570161113666150123112751

    Article  CAS  PubMed  Google Scholar 

  68. Goossens E.A.C., de Vries M.R., Simons K.H., Putter H., Quax P.H.A, Nossent A.Y. 2019. miRMap: Profiling 14q32 microRNA expression and DNA methylation throughout the human vasculature. Front Cardiovasc. Med. 6, 113. https://doi.org/10.3389/fcvm.2019.00113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Huan T., Mendelson M., Joehanes R., Yao C., Liu C., Song C., Bhattacharya A., Rong J., Tanriverdi K., Keefe J., Murabito J.M., Courchesne P., Larson M.G., Freedman J.E., Levy D. 2020. Epigenome-wide association study of DNA methylation and microRNA expression highlights novel pathways for human complex traits. Epigenetics. 15 (1–2), 183–198. https://doi.org/10.1080/15592294.2019.1640547

    Article  PubMed  Google Scholar 

  70. Edwards S.L., Beesley J., French J.D., Dunning A.M. 2013. Beyond GWASs: Illuminating the dark road from association to function. Am. J. Hum. Genet. 93 (5), 779–797. https://doi.org/10.1016/j.ajhg.2013.10.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Borghini A., Andreassi M.G. 2018. Genetic polymorphisms offer insight into the causal role of microRNA in coronary artery disease. Atherosclerosis. 269, 63–70. https://doi.org/10.1016/j.atherosclerosis.2017.12.022

    Article  CAS  PubMed  Google Scholar 

  72. Miao Y.R., Liu W., Zhang Q., Guo A.Y. 2018. lncRNASNP2: An updated database of functional SNPs and mutations in human and mouse lncRNAs. Nucleic Acids Res. 46 (D1), D276–D280. https://doi.org/10.1093/nar/gkx1004

    Article  CAS  PubMed  Google Scholar 

  73. Moszyńska A., Gebert M., Collawn J.F., Bartoszewski R. 2017. SNPs in microRNA target miRNA sites and their potential role in human disease. Open Biol. 7 (4), 170019. https://doi.org/10.1098/rsob.170019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Zhang L., Yang J., Xue Q., Yang D., Lu Y., Guang X., Zhang W., Ba R., Zhu H., Ma X. 2016. An rs13293512 polymorphism in the promoter of let-7 is associated with a reduced risk of ischemic stroke. J. Thromb. Thrombolysis. 42 (4), 610–615. https://doi.org/10.1007/s11239-016-1400-1

    Article  CAS  PubMed  Google Scholar 

  75. Cai M.Y., Cheng J., Zhou M.Y., Liang L.L., Lian S.M., Xie X.S., Xu S., Liu X., Xiong X.D. 2018. The association between pre-miR-27a rs895819 polymorphism and myocardial infarction risk in a Chinese han population. Lipids Health Dis. 17 (1), 7. https://doi.org/10.1186/s12944-017-0652-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Oner T., Arslan C., Yenmis G., Arapi B., Tel C., Aydemir B., Sultuybek G.K. 2017. Association of NFKB1A and microRNAs variations and the susceptibility to atherosclerosis. J. Genet. 96 (2), 251–259. https://doi.org/10.1007/s12041-017-0768-9

    Article  CAS  PubMed  Google Scholar 

  77. He Y., Yang J., Kong D., Lin J., Xu C., Ren H., Ouyang P., Ding Y., Wang K. 2015. Association of miR-146a rs2910164 polymorphism with cardio-cerebrovascular diseases: A systematic review and meta-analysis. Gene. 565 (2), 171–179. https://doi.org/10.1016/j.gene.2015.04.020

    Article  CAS  PubMed  Google Scholar 

  78. Xiong X.D., Cho M., Cai X.P., Cheng J., Jing X., Cen J.M., Liu X., Yang X.L., Suh Y. 2014. A common variant in pre-miR-146 is associated with coronary artery disease risk and its mature miRNA expression. Mutat. Res. 761, 15–20. https://doi.org/10.1016/j.mrfmmm.2014.01.001

    Article  CAS  PubMed  Google Scholar 

  79. Bastami M., Choupani J., Saadatian Z., Zununi Vahed S., Mansoori Y., Daraei A., Samadi Kafil H., Masotti A., Nariman-Saleh-Fam Z. 2019. Polymorphisms and risk of cardio-cerebrovascular diseases: A systematic review and meta-analysis. Int. J. Mol. Sci. 20 (2), 293. https://doi.org/10.3390/ijms20020293

    Article  CAS  PubMed Central  Google Scholar 

  80. Bao M.H., Xiao Y., Zhang Q.S., Luo H.Q., Luo J., Zhao J., Li G.Y., Zeng J., Li J.M. 2015. Meta-analysis of miR-146a polymorphisms association with coronary artery diseases and ischemic stroke. Int. J. Mol. Sci. 16 (7), 14305–14317. https://doi.org/10.3390/ijms160714305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hamann L., Glaeser C., Schulz S., Gross M., Franke A., Nöthlings U., Schumann R.R. 2014. A micro RNA-146a polymorphism is associated with coronary restenosis. Int. Immunogenet. 41 (5), 393–396. https://doi.org/10.1111/iji.12136

    Article  CAS  Google Scholar 

  82. Shen J., Zhang M., Sun M., Tang K., Zhou B. 2015. The relationship of miR-146a gene polymorphism with carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus. Thromb. Res. 136 (6), 1149–1155. https://doi.org/10.1016/j.thromres.2015.10.013

    Article  CAS  PubMed  Google Scholar 

  83. Zhu R., Liu X., He Z., Li Q. 2014. miR-146a and miR-196a2 polymorphisms in patients with ischemic stroke in the northern Chinese han population. Neurochem. Res. 39 (9), 1709–1716. https://doi.org/10.1007/s11064-014-1364-5

    Article  CAS  PubMed  Google Scholar 

  84. Zhong H., Cai Y., Cheng J., Cai D., Chen L., Su C., Li K., Chen P., Xu J., Cui L. 2016. Apolipoprotein E epsilon 4 enhances the association between the rs2910164 polymorphism of miR-146a and risk of atherosclerotic cerebral infarction. J. Atheroscler. Thromb. 23 (7), 819–829. https://doi.org/10.5551/jat.32904

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Jeon Y.J., Kim O.J., Kim S.Y., Oh S.H., Oh D., Kim O.J., Shin B.S., Kim N.K. 2013). Association of the miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms with ischemic stroke and silent brain infarction risk. Arterioscler. Thromb. Vasc. Biol. 33 (2), 420–430. https://doi.org/10.1161/ATVBAHA.112.300251

    Article  CAS  PubMed  Google Scholar 

  86. Zhu J., Yue H., Qiao C., Li Y. 2015. Association between single-nucleotide polymorphism (SNP. in miR-146a, miR-196a2, and miR-499 and risk of ischemic stroke: A meta-analysis. Med. Sci. Monit. 21, 3658–3663. https://doi.org/10.12659/msm.895233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Qu J.Y., Xi J., Zhang Y.H., Zhang C.N., Song L., Song Y., Hui R.T., Chen J.Z. 2016. Association of the microRNA-146a SNP rs2910164 with ischemic stroke incidence and prognosis in a Chinese population. Int. J. Mol. Sci. 17 (5), 660. https://doi.org/10.3390/ijms17050660

    Article  CAS  PubMed Central  Google Scholar 

  88. Sung J.H., Kim S.H., Yang W.I., Kim W.J., Moon J.Y., Kim I.J., Cha D.H., Cho S.Y., Kim J.O., Kim K.A., Kim O.J., Lim S.W., Kim N.K. 2016. miRNA polymorphisms (miR‑146a, miR‑149, miR‑196a2 and miR‑499. are associated with the risk of coronary artery disease. Mol. Med. Rep. 14 (3), 2328–2342. https://doi.org/10.3892/mmr.2016.5495

    Article  CAS  PubMed  Google Scholar 

  89. Zhi H., Wang L., Ma G., Ye X., Yu X., Zhu Y., Zhang Y., Zhang J., Wang B. 2012. Polymorphisms of miRNAs genes are associated with the risk and prognosis of coronary artery disease. Clin. Res. Cardiol. 101 (4), 289–296.https://doi.org/10.1007/s00392-011-0391-3

    Article  CAS  PubMed  Google Scholar 

  90. Osmak G.Zh., Matveeva N.A., Titov B.V., Favorova O.O. 2018. The myocardial infarction associated variant in the MIR196A2 gene and presumable signaling pathways to involve miR-196a2 in the pathological phenotype. Mol. Biol. (Moscow). 52 (6), 872–877.

    Article  CAS  Google Scholar 

  91. Kim J., Choi G.H., Ko K.H., Kim J.O., Oh S.H., Park Y.S., Kim O.J., Kim N.K. 2016. Association of the single nucleotide polymorphisms in microRNAs 130b, 200b, and 495 with ischemic stroke susceptibility and post-stroke mortality. PLoS One. 11 (9), e0162519. https://doi.org/10.1371/journal.pone.0162519

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Jha C.K., Mir R., Elfaki I., Khullar N., Rehman S., Javid J., Banu S., Chahal S. 2019. Potential impact of microRNA-423 gene variability in coronary artery disease. Endocr. Metab. Immune Disord. Drug Targets. 19 (1), 67–74. https://doi.org/10.2174/1871530318666181005095724

    Article  CAS  PubMed  Google Scholar 

  93. Chen C., Hong H., Chen L., Shi X., Chen Y., Weng Q. 2014. Association of microRNA polymorphisms with the risk of myocardial infarction in a Chinese population. Tohoku J. Exp. Med. 233 (2), 89–94. https://doi.org/10.1620/tjem.233.89

    Article  CAS  PubMed  Google Scholar 

  94. Darabi H., Salmaninejad A., Jaripour M.E., Azarpazhooh M.R., Mojarrad M., Sadr-Nabavi A. 2019. Association of the genetic polymorphisms in immunoinflammatory microRNAs with risk of ischemic stroke and subtypes in an Iranian population. J. Cell. Physiol. 234 (4), 3874–3886. https://doi.org/10.1002/jcp.27159

    Article  CAS  PubMed  Google Scholar 

  95. Liu Y., Ma Y., Zhang B., Wang S.X., Wang X.M., Yu J.M. 2014. Genetic polymorphisms in pre-microRNAs and risk of ischemic stroke in a Chinese population. J. Mol. Neurosci. 52 (4), 473–480. https://doi.org/10.1007/s12031-013-0152-z

    Article  CAS  PubMed  Google Scholar 

  96. Zhang Z., Xu G., Cai B., Zhang H., Zhu W., Liu X. 2017. Genetic variants in microRNAs predict recurrence of ischemic stroke. Mol. Neurobiol. 54 (4), 2776–2780. https://doi.org/10.1007/s12035-016-9865-7

    Article  CAS  PubMed  Google Scholar 

  97. Ghanbari M., de Vries P.S., de Looper H., Peters M.J., Schurmann C., Yaghootkar H., Dörr M., Frayling T.M., Uitterlinden A.G., Hofman A., van Meurs J.B., Erkeland S.J., Franco O.H., Dehghan A. 2014. A genetic variant in the seed region of miR-4513 shows pleiotropic effects on lipid and glucose homeostasis, blood pressure, and coronary artery disease. Hum. Mutat. 35 (12), 1524–1531. https://doi.org/10.1002/humu.22706

    Article  CAS  PubMed  Google Scholar 

  98. Reference SNP (rs. Report: rs2910164). 2021. https://www.ncbi.nlm.nih.gov/snp/rs2910164.

  99. Li Q., Chen L., Chen D., Wu X., Chen M. 2015. Influence of microRNA-related polymorphisms on clinical outcomes in coronary artery disease. Am. J. Transl. Res. 7 (2), 393–400.

    PubMed  PubMed Central  Google Scholar 

  100. Ensembl rs4225 SNP Allele: Frequency count. 2021. https://www.ensembl.org/Homo_sapiens/Variation/ Population?db=core;r=11:116832455-116833455;v= rs4225;vdb=variation;vf=164407333.

  101. Hu S.L., Cui G.L., Huang J., Jiang J.G., Wang D.W. 2016. An APOC3 3'UTR variant associated with plasma triglycerides levels and coronary heart disease by creating a functional miR-4271 binding site. Sci. Rep. 6, 32700. https://doi.org/10.1038/srep32700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Wagschal A., Najafi-Shoushtari S.H., Wang L., Goedeke L., Sinha S., deLemos A.S., Black J.C., Ramírez C.M., Li Y., Tewhey R., Hatoum I., Shah N., Lu Y., Kristo F., Psychogios N., et al. 2015. Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis. Nat. Med. 21 (11), 1290–1297. https://doi.org/10.1038/nm.3980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Jazdzewski K., Murray E.L., Franssila K., Jarzab B., Schoenberg D.R., de la Chapelle A. 2008. Common SNP in pre-miR-146a decreases mature miR expression and predisposes to papillary thyroid carcinoma. Proc. Natl. Acad. Sci. U. S. A. 105 (20), 7269–7274. https://doi.org/10.1073/pnas.0802682105

    Article  PubMed  PubMed Central  Google Scholar 

  104. Wang D., Atanasov A.G. 2019. The microRNAs regulating vascular smooth muscle cell proliferation: A minireview. Int. J. Mol. Sci. 20 (2), 324. https://doi.org/10.3390/ijms20020324

    Article  CAS  PubMed Central  Google Scholar 

  105. Sun X., Icli B., Wara A.K., Belkin N., He S., Kobzik L., Hunninghake G.M., Vera M.P., MICU Registry, Blackwell T.S., Baron R.M., Feinberg M.W. 2012. MicroRNA-181b regulates NF-κB-mediated vascular inflammation. J. Clin. Invest. 122 (6), 1973–1990. https://doi.org/10.1172/JCI61495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Dweep H., Georgiou G.D., Gretz N., Deltas C., Voskarides K., Felekkis K. 2013. CNVs-microRNAs interactions demonstrate unique characteristics in the human genome. An interspecies in silico analysis. PLoS One. 8 (12), e81204. https://doi.org/10.1371/journal.pone.0081204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Marcinkowska M., Szymanski M., Krzyzosiak W.J., Kozlowski P. 2011. Copy number variation of microRNA genes in the human genome. BMC Genomics. 12, 183. https://doi.org/10.1186/1471-2164-12-183

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Sohrabifar N., Ghaderian S., Vakili H., Ghaedi H., Rouhani B., Jafari H., Heidari L. 2021. MicroRNA-copy number variations in coronary artery disease patients with or without type 2 diabetes mellitus. Arch. Physiol. Biochem. 127 (6), 497–503. https://doi.org/10.1080/13813455.2019.1651340

    Article  CAS  PubMed  Google Scholar 

  109. Nazarenko M.S., Sleptcov A.A., Lebedev I.N., Skryabin N.A., Markov A.V., Golubenko M.V., Koroleva I.A., Kazancev A.N., Barbarash O.L., Puzyrev V.P. 2017. Genomic structural variations for cardiovascular and metabolic comorbidity. Sci. Rep. 7, 41268. https://doi.org/10.1038/srep41268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Lins T.C. de L. 2014. Variação estrutural no número de cópias e sua implicação na expressão de microRNA em humanos. https://repositorio.unb.br/handle/10482/16506.

  111. Xing H.J., Li Y.J., Ma Q.M., Wang A.M., Wang J.L., Sun M., Jian Q., Hu J.H., Li D., Wang L. 2013. Identification of microRNAs present in congenital heart disease associated copy number variants. Eur. Rev. Med. Pharmacol Sci. 17 (15), 2114–2120.

    PubMed  Google Scholar 

  112. Chen L.J., Lim S.H., Yeh Y.T., Lien S.C., Chiu J.J. 2012. Roles of microRNAs in atherosclerosis and restenosis. J. Biomed. Sci. 19 (1), 79. https://doi.org/10.1186/1423-0127-19-79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Schober A., Weber C. 2016. Mechanisms of microRNAs in atherosclerosis. Annu. Rev. Pathol. 11, 583–616. https://doi.org/10.1146/annurev-pathol-012615-044135

    Article  CAS  PubMed  Google Scholar 

  114. Johnson J.L. 2019. Elucidating the contributory role of microRNA to cardiovascular diseases (a review). Vascul. Pharmacol. 114, 31–48. https://doi.org/10.1016/j.vph.2018.10.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Tao J., Xia L., Cai Z., Liang L., Chen Y., Meng J., Wang Z. 2021. Interaction between microRNA and DNA methylation in atherosclerosis. DNA Cell Biol. 40 (1), 101–115. https://doi.org/10.1089/dna.2020.6138

    Article  CAS  PubMed  Google Scholar 

  116. Mens M., Maas S., Klap J., Weverling G.J., Klatser P., Brakenhoff J., van Meurs J., Uitterlinden A.G., Ikram M.A., Kavousi M., Ghanbari M. 2020. Multi-omics analysis reveals microRNAs associated with cardiometabolic traits. Front Genet. 11, 110. https://doi.org/10.3389/fgene.2020.00110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Vohra M., Sharma A.R., Prabhu B.N., Rai P.S. 2020. SNPs in sites for DNA methylation, transcription factor binding, and miRNA targets leading to allele-specific gene expression and contributing to complex disease risk: A systematic review. Public Health Genomics. 23 (5–6), 155–170. https://doi.org/10.1159/000510253

    Article  PubMed  Google Scholar 

Download references

Funding

The study was funded by the Russian Foundation for Basic Research, project number no. 20-115-50414.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. S. Nazarenko.

Ethics declarations

The authors declare that they have no conflicts of interest.

This article does not include any research involving humans or animals as research subjects.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nazarenko, M.S., Koroleva, I.A., Zarubin, A.A. et al. miRNA Regulome in Different Atherosclerosis Phenotypes. Mol Biol 56, 166–181 (2022). https://doi.org/10.1134/S0026893322020108

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0026893322020108

Keywords:

Navigation