МикроРНК как потенциальный маркер острой ишемии миокарда

В настоящее время для диагностики острого инфаркта миокарда не существует абсолютного биомаркера, обладающего максимально возможными специфичностью и чувствительностью. Большим потенциалом в качестве новых ранних биомаркеров для ведения пациентов с острым коронарным синдромом обладают циркулирующие микроРНК, которые не только регулируют ключевые функции в здоровом сердце, но и имеют важное значение в механизмах сердечно-сосудистых заболеваний, таких как гипертрофия миокарда, фиброз и апоптоз. В данном литературном обзоре обобщены современные представления о роли микроРНК в развитии атеросклеротических бляшек на всех стадиях атерогенеза, диагностическая ценность малых молекул в качестве биомаркера инфаркта миокарда и проведения дифференциальной диагностики данного патологического состояния с нестабильной стенокардией. Несмотря на большой интерес к проблеме и значительное количество научных работ, необходимо дальнейшее проведение исследований. Перспектива в изучении микроРНК существенно расширяет спектр диагностических возможностей данным методом.

1. Вельков В. В. Высокочувствительное измерение кардиальных тропонинов: тест, который спасает жизни. Клинико-лабораторный консилиум. Научно-практический журнал. 2012; 1 (41): 47–52

2. Apple F. S. A new season for cardiac troponin assays: it’s time to keep a scorecard. Clin Chem. 2009; 55: 1303–1306.

3. Jaffe A. S. Troponin – past, present and future. Curr Probl Cardiol. 2012; 37 (6): 209–228.

4. Lippi G., Montagnana M., Aloe R., Cervellin G. High sensitive troponin immunoassays: navigating between the scylla and charybdis. Adv Clin Chem. 2012; 58: 1–29.

5. Ndrepepa G., Braun S., Mehilli J., et al. Prognostic value of sensitive troponin T in patients with stable and unstable angina and undetectable conventional troponin. Am Heart J. 2011; 161: 68–75.

6. Lankeit M., Friesen D., Aschoff J., et al. Highly sensitive troponin T assay in normotensive patients with acute pulmonary embolism. Eur Heart J. 2010; 31: 1836–1844.

7. Filusch A., Giannitsis E., Katus H. A., et al. High-sensitive troponin T: a novel biomarker for prognosis and disease severity in patients with pulmonary arterial hypertension. Clin Sci (Lond). 2010; 119: 207–213.

8. De Lemos J. A., Drazner M. H., Omland T., et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010; 304.: 2503–2512.

9. Fang Z., Du R., Edwards A., Flemington E. K., and Zhang K. The sequence structures of human microRNA molecules and their implications. PLOS One. 2013; 8: e54215.

10. Wang J, Liew OW, Richards AM, Chen YT. Overview of microRNAs in cardiac hypertrophy, fibrosis, and apoptosis. Int J Mol Sci. 2016; 17: 749.

11. Hanson E. K., Lubenow H., Ballantyne J. Identification of forensically relevant body fluids using a panel of differentially expressed microRNAs. Anal Biochem. 2009; 387: 303–314.

12. Allegra A., Alonci A., Campo S. et al. Circulating microRNAs: new biomarkers in diagnosis, prog-nosis and treatment of cancer (review). Int. J. Oncol. 2012; 41 (6): 1897–1912.

13. Xiao Y. F., Yong X., Fan Y. H. et al. MicroRNA detection in feces, sputum, pleural effusion and urine: novel tools for cancer screening (Review). Oncol. Rep. 2013; 30 (2): 535–544.

14. Raposo G.; Stoorvogel W. Extracellular vesicles: Exosomes, microvesicles, and friends. J. Cell Biol. 2013; 200: 373–383.

15. Arroyo J. D., Chevillet J. R., Kroh E. M., Ruf I. K., Pritchard C. C., Gibson D. F., Mitchell P. S., Bennett C. F., Pogosova-Agadjanyan E.L., Stirewalt D. L. et al. Argonaute 2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc. Natl. Acad. Sci. 2011; 108: 5003–5008.

16. Vickers K. C., Palmisano B. T., Shoucri, B.M.; Shamburek R. D., Remaley A. T. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat. Cell. Biol. 2011; 13: 423–433.

17. Cipollone F., Felicioni L., Sarzani R., Ucchino S., Spigonardo F., MandoliniC., Malatesta S., Bucci, M., Mammarella, C., Santovito, D., de Lutiis, F., Marchetti, A., Mezzetti A., Buttitta F. A unique microRNA signature associated with plaque instability in humans. Stroke. 2011; 42: 2556–2563.

18. Maitrias P., Metzinger Le Meuth V., Massy Z. A., M’Baya Moutoula E., Reix T., Caus T., Metzinger L. MicroRNA deregulation in symptomatic carotid plaque. J. Vasc. Surg. 2015; 62: 1245–1250.

19. Bazan H. A., Hatfield S. A., O’Malley C.B., Brooks A. J., Lightell D., Jr., Woods T. C. Acute loss of miR!221 and miR 222 in the atherosclerotic plaque shoulderaccompanies plaque rupture. Stroke. 2015; 46: 3285–3287.

20. 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. Overexpression of microRNA‑145 in atherosclerotic plaques from hypertensive patients. Expert Opin. Ther. Targets. 2013; 17: 217–223.

21. Wezel A., Welten S. M., Razawy W., Lagraauw H. M., De Vries M. R., Goossens E. A., Boonstra M. C., Hamming J. F., Kandimalla E. R., Kuiper J., Quax P. H., Nossent A. Y., Bot I. Inhibition of microRNA!494 reduces carotid artery atherosclerotic lesion development and increases plaque stability. Ann. Surg. 2015; 262: 841–847.

22. Markus B., Grote K., Worsch M., Parviz B., Boening A., Schieffer B., Parahuleva M. S. Differential expression of microRNAs in endarterectomy specimens taken from patients with asymptomatic and symptomatic carotid plaques. PLoS One. 2016; 11: e0161632.

23. Wang R., Dong L. D., Meng X. B., Shi Q., Sun, W. Y. Unique microRNA signatures associated with early coronary atherosclerotic plaques. Biochem. Biophys. Res. Commun. 2015; 464: 574–579.

24. Li S, Lee C, Song J, Lu C, Liu J, Cui Y, et al. Circulating microRNAs as potential biomarkers for coronary plaque rupture. Oncotarget. 2017; 8: 48145–48156.

25. Cheng C, Wang Q, You W, Chen M, Xia J. MiRNAs as biomarkers of myocardial infarction: a meta-analysis. PLoS One. 2014; 9: e88566.

26. Wang Q, Ma J, Jiang Z, Wu F, Ping J, Ming L. Identification of microRNAs as diagnostic biomarkers for acute myocardial infarction in Asian populations: A systematic review and meta-analysis. Medicine (Baltimore). 2017; 96: e7173.

27. Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, et al. Circulating microRNA‑208b and microRNA‑499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet. 2010; 3: 499–506.

28. Liu X, Fan Z, Zhao T, Cao W, Zhang L, Li H, et al. Plasma miR‑1, miR 208, miR-499 as potential predictive biomarkers for acute myocardial infarction: An independent study of Han population. Exp Gerontol. 2015; 72: 230–238.

29. Bialek S, Gorko D, Zajkowska A, Koltowski L, Grabowski M, Stachurska A, et al. Release kinetics of circulating miRNA‑208a in the early phase of myocardial infarction. Kardiol Pol. 2015; 73: 613–619.

30. D’Alessandra Y, Devanna P, Limana F, Straino S, Di Carlo A, Brambilla PG, et al. Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J. 2010; 31: 2765–2773.

31. Widera C, Gupta SK, Lorenzen JM, Bang C, Bauersachs J, Bethmann K, et al. Diagnostic and prognostic impact of six circulating microRNAs in acute coronary syndrome. J Mol Cell Cardiol. 2011; 51: 872–875.

32. Devaux Y, Vausort M, Goretti E, Nazarov PV, Azuaje F, Gilson G, et al. Use of Circulating MicroRNAs to Diagnose Acute Myocardial Infarction. Clin Chem. 2012; 58: 559–567.

33. Oerlemans MI, Mosterd A, Dekker MS, de Vrey EA, van Mil A, Pasterkamp G, et al. Early assessment of acute coronary syndromes in the emergency department: the potential diagnostic value of circulating microRNAs. EMBO Mol Med. 2012; 4: 1176–1185.

34. Gidlöf O, Smith JG, Miyazu K, Gilje P, Spencer A, Blomquist S, et al. Circulating cardio-enriched microRNAs are associated with longterm prognosis following myocardial infarction. BMC Cardiovasc Disord. 2013; 13: 12.

35. Devaux Y, Mueller M, Haaf P, Goretti E, Twerenbold R, Zangrando J, et al. Diagnostic and prognostic value of circulating microRNAs in patients with acute chest pain. J Intern Med. 2015; 277: 260–271.

36. Zhang Y, Cheng J, Chen F, Wu C, Zhang J, Ren X, et al. Circulating endothelial microparticles and miR‑92a in acute myocardial infarction. Biosci Rep. 2017; 37: BSR 20170047.