МикроРНК в диагностике хронической сердечной недостаточности: состояние проблемы и результаты пилотного исследования

1. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116 (2): 281–97. doi: 10.1016/S0092-8674(04)00045-5.
2. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120 (1): 15–20.
3. Iaconetti С, Gareri С, Polimeni А, and CiroIndolfi: Non-CodingRNAs. The “DarkMatter” of Cardiovascular Pathophysiology. Int J Mol Sci 2013; 14 (10): 19987–20018.
4. Chim SS et al. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem 2008; 54: 482–90.
5. Chen X, Ba Y, Ma L et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008; 18: 997–1006.
6. Weber JA, Baxter DH, Zhang S et al. The microRNA spectrum in 12 body fluids. Clin Chem 2010; 56: 1733–41.
7. Turchinovich A, Weiz L, Burwinkel B.. Extracellular miRNAs: the mystery of their origin and function. Trends Biochem Sci (2012) 37:460–5
8. Tijsen AJ, Creemers EE, Moerland PD et al. MiR423-5p as a circulating biomarker for heart failure. Circ Res 2010; 106: 1035–9.
9. Goren Y, Kushnir M, Zafrir B et al. Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail 2012; 14: 147–54.
10. Fan KL, Zhang HF, Shen J et al. Circulating microRNAs levels in Chinese heart failure patients caused by dilated cardiomyopathy. Indian Heart J 2013; 65 (1): 12–6.
11. Tutarel O, Dangwal S, Bretthauer J. Circulating miR-423_5p fails as a biomarker for systemic ventricular function in adults after atrial repair for transposition of the great arteries. Int J Cardiol 2013; 167 (1): 63–6.
12. Bauters C, Kumarswamy R, Holzmann A et al. Circulating miR-133a and miR-423-5p fail as biomarkers for left ventricular remodeling after myocardial infarction. Int J Cardiol 2013; 168: 1837–40.
13. Ji R, Cheng Y, Yue J et al. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res 2007; 100: 1579–88.
14. Suárez Y, Fernández-Hernando C, Pober JS, Sessa WC. Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res 2007; 100: 1164–73.
15. Cheng Y, Ji R, Yue J et al. Micro RNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy? Am J Pathol 2007; 170: 1831–40.
16. Roy S, Khanna S, Hussain SR et al. MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. Cardiovasc Res 2009; 82: 21–9.
17. Banjo T, Grajcarek J, Yoshino D et al. Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21. Nat Commun 2013; 4: 1978.
18. Thum T, Gross C, Fiedler J et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456 (7224): 980–4.
19. Cheng Y, Liu X, Zhang S et al. MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4. J Mol Cell Cardiol 2009; 47 (1): 5–14.
20. Sayed D, Rane S, Lypowy J et al. MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol Biol Cell 2008; 19 (8): 3272–82.
21. Matkovich SJ, Van Booven DJ, Youker KA et al. Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support. Circulation 2009; 119 (9): 1263–71.
22. Dong S, Cheng Y, Yang J et al. MicroRNA expression signature and the role of microRNA-21 in the early phase of acute myocardial infarction. J Biol Chem 2009; 284 (43): 29514–25.
23. Thum T, Galuppo P, Wolf C et al. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure.Circulation 2007; 116 (3): 258–67.
24. Sayed D, Hong C, Chen IY et al. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res 2007; 100 (3): 416–24.
25. Bang C, Batkai S, Dangwal S et al. Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J Clin Invest 2014; 124 (5): 2136–46. doi: 10.1172/jci70577.
26. Cheng H et al. Loss of enigma homolog protein results in dilated cardiomyopathy. Circ Res 2010; 107 (3): 348–6. doi: 10.1161/CIRCRESAHA.110.218735.
27. Ye X et al. Coxsackievirus-induced miR-21 disrupts cardiomyocyte interactions via the downregulation of intercalated disc components. PLoS Pathog 2014; 10; e1004070.
28. Cardin S, Guasch E, Luo X et al. Role for microRNA-21 in atrial profibrillatory fibrotic remodeling associated with experimental postinfarction heart failure. Circ Arrhythm J Electrophysiol 2012; 5: 1027–35.
29. Nishi, Hiroyuki et al. Impact of microRNA Expression in Human Atrial Tissue in Patients with Atrial Fibrillation Undergoing Cardiac Surgery. PLoS ONE 2013; 8 (9): e73397. PMC. Web.
30. Yamakuchi M, Ferlito M, Lowenstein CJ. miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA 2008; 105 (36): 13421–6.
31. Boon RA, Iekushi K, Lechner S et al. MicroRNA-34a regulates cardiac ageing and function. Nature 2013; 495 (7439): 107–10.
32. Bernardo BC, Gao XM, Winbanks CE et al. Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodeling and improves heart function. Proc Natl Acad Sci USA 2012; 109 (43): 17615–20.
33. Bernardo BC, Gao X-M, Tham YK et al. Silencing of miR-34a Attenuates Cardiac Dysfunction in a Setting of Moderate, but Not Severe, Hypertrophic Cardiomyopathy. PLoS ONE 2014; 9 (2): e90337. doi:10.1371/journal.pone.0090337.
34. Huang Y, Qi Y, Du JQ, Zhang DF. MicroRNA-34a regulates cardiac fibrosis after myocardial infarction by targeting Smad4. Exp Opin Ther Targets 2014; 18 (12): 1355–65.
35. Fan F, Sun A, Zhao H et al. MicroRNA-34apromotes cardiomyocyte apoptosis post myocardial infarction through down-regulating aldehyde dehydrogenase 2. Curr Pharm Des 2013; 19 (27): 4865–73.
36. van Rooij E, Liu N, Olson EN. MicroRNAs flex their muscles. Trends Genet 2008; 24 (4): 159–66.
37. Boon RA, Iekushi K, Fischer A et al. Inhibition of the Age-induced microRNA-34 Improves Recovery After AMI in Mice. Circulation 2010; 122: A14023.
38. Matkovich SJ, Hu YX, Eschenbacher WH et al. Direct and indirect involvement of microRNA-499 in clinical and experimental cardiomyopathy. Circ Res 2012; 111: 521–31.
39. Montgomery RL, Hullinger TG, Semus HM et al. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure. Circulation 2011; 124 (14): 1537–47.
40. Callis TE, Pandya K, Seok HY et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest 2009; 119: 2772–86.
41. Ji X, Takahashi R, Hiura Y et al. Plasma mir-208 as a biomarker of myocardial injury. Clin Chem 2009; 55: 1944–9.
42. van Rooij E, Sutherland LB,. Qi XX et al. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 2007; 316: 575–9.
43. Corsten MF, Dennert R,  Jochems S 4et al. Circulating MicroRNA-208b and MicroRNA-499 Reflect Myocardial Damage in Cardiovascular Disease. Circulation Cardiovasc Gen 2010; 3: 499–506.
44. Gidlöf O, Smith JG, Miyazu K et al. Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction. BMC Cardiovasc Dis 2013; 13: 12. doi:10.1186/1471-2261-13-12.
45. Gidlöf O, Andersson P, van der Pals J et al. Cardiospecific microRNA Plasma Levels Correlate with Troponin and Cardiac Function in Patients with ST Elevation Myocardial Infarction, Are Selectively Dependent on Renal Elimination, and Can Be Detected in Urine Samples. Cardiology 2011; 118: 217–6.
46. Wang GK, Zhu JQ, Zhang JT et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 2010; 31: 659–66.

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1. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116 (2): 281–97. doi: 10.1016/S0092-8674(04)00045-5.
2. Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120 (1): 15–20.
3. Iaconetti С, Gareri С, Polimeni А, and CiroIndolfi: Non-CodingRNAs. The “DarkMatter” of Cardiovascular Pathophysiology. Int J Mol Sci 2013; 14 (10): 19987–20018.
4. Chim SS et al. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem 2008; 54: 482–90.
5. Chen X, Ba Y, Ma L et al. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 2008; 18: 997–1006.
6. Weber JA, Baxter DH, Zhang S et al. The microRNA spectrum in 12 body fluids. Clin Chem 2010; 56: 1733–41.
7. Turchinovich A, Weiz L, Burwinkel B.. Extracellular miRNAs: the mystery of their origin and function. Trends Biochem Sci (2012) 37:460–5
8. Tijsen AJ, Creemers EE, Moerland PD et al. MiR423-5p as a circulating biomarker for heart failure. Circ Res 2010; 106: 1035–9.
9. Goren Y, Kushnir M, Zafrir B et al. Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail 2012; 14: 147–54.
10. Fan KL, Zhang HF, Shen J et al. Circulating microRNAs levels in Chinese heart failure patients caused by dilated cardiomyopathy. Indian Heart J 2013; 65 (1): 12–6.
11. Tutarel O, Dangwal S, Bretthauer J. Circulating miR-423_5p fails as a biomarker for systemic ventricular function in adults after atrial repair for transposition of the great arteries. Int J Cardiol 2013; 167 (1): 63–6.
12. Bauters C, Kumarswamy R, Holzmann A et al. Circulating miR-133a and miR-423-5p fail as biomarkers for left ventricular remodeling after myocardial infarction. Int J Cardiol 2013; 168: 1837–40.
13. Ji R, Cheng Y, Yue J et al. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res 2007; 100: 1579–88.
14. Suárez Y, Fernández-Hernando C, Pober JS, Sessa WC. Dicer dependent microRNAs regulate gene expression and functions in human endothelial cells. Circ Res 2007; 100: 1164–73.
15. Cheng Y, Ji R, Yue J et al. Micro RNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy? Am J Pathol 2007; 170: 1831–40.
16. Roy S, Khanna S, Hussain SR et al. MicroRNA expression in response to murine myocardial infarction: miR-21 regulates fibroblast metalloprotease-2 via phosphatase and tensin homologue. Cardiovasc Res 2009; 82: 21–9.
17. Banjo T, Grajcarek J, Yoshino D et al. Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21. Nat Commun 2013; 4: 1978.
18. Thum T, Gross C, Fiedler J et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456 (7224): 980–4.
19. Cheng Y, Liu X, Zhang S et al. MicroRNA-21 protects against the H(2)O(2)-induced injury on cardiac myocytes via its target gene PDCD4. J Mol Cell Cardiol 2009; 47 (1): 5–14.
20. Sayed D, Rane S, Lypowy J et al. MicroRNA-21 targets Sprouty2 and promotes cellular outgrowths. Mol Biol Cell 2008; 19 (8): 3272–82.
21. Matkovich SJ, Van Booven DJ, Youker KA et al. Reciprocal regulation of myocardial microRNAs and messenger RNA in human cardiomyopathy and reversal of the microRNA signature by biomechanical support. Circulation 2009; 119 (9): 1263–71.
22. Dong S, Cheng Y, Yang J et al. MicroRNA expression signature and the role of microRNA-21 in the early phase of acute myocardial infarction. J Biol Chem 2009; 284 (43): 29514–25.
23. Thum T, Galuppo P, Wolf C et al. MicroRNAs in the human heart: a clue to fetal gene reprogramming in heart failure.Circulation 2007; 116 (3): 258–67.
24. Sayed D, Hong C, Chen IY et al. MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res 2007; 100 (3): 416–24.
25. Bang C, Batkai S, Dangwal S et al. Cardiac fibroblast-derived microRNA passenger strand-enriched exosomes mediate cardiomyocyte hypertrophy. J Clin Invest 2014; 124 (5): 2136–46. doi: 10.1172/jci70577.
26. Cheng H et al. Loss of enigma homolog protein results in dilated cardiomyopathy. Circ Res 2010; 107 (3): 348–6. doi: 10.1161/CIRCRESAHA.110.218735.
27. Ye X et al. Coxsackievirus-induced miR-21 disrupts cardiomyocyte interactions via the downregulation of intercalated disc components. PLoS Pathog 2014; 10; e1004070.
28. Cardin S, Guasch E, Luo X et al. Role for microRNA-21 in atrial profibrillatory fibrotic remodeling associated with experimental postinfarction heart failure. Circ Arrhythm J Electrophysiol 2012; 5: 1027–35.
29. Nishi, Hiroyuki et al. Impact of microRNA Expression in Human Atrial Tissue in Patients with Atrial Fibrillation Undergoing Cardiac Surgery. PLoS ONE 2013; 8 (9): e73397. PMC. Web.
30. Yamakuchi M, Ferlito M, Lowenstein CJ. miR-34a repression of SIRT1 regulates apoptosis. Proc Natl Acad Sci USA 2008; 105 (36): 13421–6.
31. Boon RA, Iekushi K, Lechner S et al. MicroRNA-34a regulates cardiac ageing and function. Nature 2013; 495 (7439): 107–10.
32. Bernardo BC, Gao XM, Winbanks CE et al. Therapeutic inhibition of the miR-34 family attenuates pathological cardiac remodeling and improves heart function. Proc Natl Acad Sci USA 2012; 109 (43): 17615–20.
33. Bernardo BC, Gao X-M, Tham YK et al. Silencing of miR-34a Attenuates Cardiac Dysfunction in a Setting of Moderate, but Not Severe, Hypertrophic Cardiomyopathy. PLoS ONE 2014; 9 (2): e90337. doi:10.1371/journal.pone.0090337.
34. Huang Y, Qi Y, Du JQ, Zhang DF. MicroRNA-34a regulates cardiac fibrosis after myocardial infarction by targeting Smad4. Exp Opin Ther Targets 2014; 18 (12): 1355–65.
35. Fan F, Sun A, Zhao H et al. MicroRNA-34apromotes cardiomyocyte apoptosis post myocardial infarction through down-regulating aldehyde dehydrogenase 2. Curr Pharm Des 2013; 19 (27): 4865–73.
36. van Rooij E, Liu N, Olson EN. MicroRNAs flex their muscles. Trends Genet 2008; 24 (4): 159–66.
37. Boon RA, Iekushi K, Fischer A et al. Inhibition of the Age-induced microRNA-34 Improves Recovery After AMI in Mice. Circulation 2010; 122: A14023.
38. Matkovich SJ, Hu YX, Eschenbacher WH et al. Direct and indirect involvement of microRNA-499 in clinical and experimental cardiomyopathy. Circ Res 2012; 111: 521–31.
39. Montgomery RL, Hullinger TG, Semus HM et al. Therapeutic Inhibition of miR-208a Improves Cardiac Function and Survival During Heart Failure. Circulation 2011; 124 (14): 1537–47.
40. Callis TE, Pandya K, Seok HY et al. MicroRNA-208a is a regulator of cardiac hypertrophy and conduction in mice. J Clin Invest 2009; 119: 2772–86.
41. Ji X, Takahashi R, Hiura Y et al. Plasma mir-208 as a biomarker of myocardial injury. Clin Chem 2009; 55: 1944–9.
42. van Rooij E, Sutherland LB,. Qi XX et al. Control of stress-dependent cardiac growth and gene expression by a microRNA. Science 2007; 316: 575–9.
43. Corsten MF, Dennert R,  Jochems S 4et al. Circulating MicroRNA-208b and MicroRNA-499 Reflect Myocardial Damage in Cardiovascular Disease. Circulation Cardiovasc Gen 2010; 3: 499–506.
44. Gidlöf O, Smith JG, Miyazu K et al. Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction. BMC Cardiovasc Dis 2013; 13: 12. doi:10.1186/1471-2261-13-12.
45. Gidlöf O, Andersson P, van der Pals J et al. Cardiospecific microRNA Plasma Levels Correlate with Troponin and Cardiac Function in Patients with ST Elevation Myocardial Infarction, Are Selectively Dependent on Renal Elimination, and Can Be Detected in Urine Samples. Cardiology 2011; 118: 217–6.
46. Wang GK, Zhu JQ, Zhang JT et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 2010; 31: 659–66.

И.В.Жиров*1, А.Г.Кочетов1,2, А.В.Засеева1, О.В.Лянг2, А.А.Скворцов1, А.А.Абрамов3, Р.Р.Гимадиев1, В.П.Масенко1, С.Н.Терещенко1

1 Институт клинической кардиологии им. А.Л.Мясникова ФГБУ Российский кардиологический научно-производственный комплекс Минздрава России. 121552, Россия, Москва, ул. 3-я Черепковская, д. 15а;
2 ФГАОУ ВО Российский университет дружбы народов. 117198, Россия, Москва, ул. Миклухо-Маклая, д. 6;
3 ГБУЗ Научно-практический центр медицинской помощи детям с пороками развития черепно-лицевой области и врожденными заболеваниями нервной системы. 119620, Россия, Москва, ул. Авиаторов, д. 38
*izhirov@mail.ru

________________________________________________

I.V.Zhirov*1, A.G.Kochetov1,2, A.V.Zaseeva1, O.V.Liang2, A.A.Skvortsov1, A.A.Abramov3, R.R.Gimadiev1, V.P.Masenko1, S.N.Tereshchenko1

1 A.L.Myasnikov Institute of Clinical Cardiology, Russian Cardiological Scientific-Industrial Complex of the Ministry of Health of the Russian Federation. 121552, Russian Federation, Moscow, ul. 3-ia Cherepkovskaia, d. 15a;
2 People’s Friendship University of Russia. 117198, Russian Federation, Moscow, ul. Miklukho-Maklaya, d. 6;
3 Scientific and practical center of medical aid to children with congenital abnormality of craniofacial area and congenital diseases of the nervous system.119620, Russian Federation, Moscow, ul. Aviatorov, d. 38
*izhirov@mail.ru