Characterisation of circulating microRNA-21 levels in patients with hypertrophic cardiomyopathy

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Abstract

Aim. To study the levels of circulating microRNA-21 in patients with hypertrophic cardiomyopathy (HCM) of different ages.

Materials and methods. The study included 49 patients with HCM. The proportion of females was 55.1%, males – 44.9%. The average age was 50 [32; 65] (from 19 to 86 years). The control group for microRNA-21 included 44 healthy individuals, respectively, matched by the age and sex with the studied patients. Patients was made in accordance with the recommendations of the European society of cardiology. Plasma microRNA expression was determined by PCR with reverse transcription and real-time detection of results. The relative level of gene expression was calculated in accordance with the standard procedure 2-ÄCt.

Results. Septal wall thickness at end diastole has a significant negative correlation with age in patients with HCM (r=-0.56; р<0.001). PWTd (posterior wall thickness at end diastole) has a significant positive correlation with age in patients with HCM (r=0.67, р<0.001).

The level of circulating microRNA-21 in plasma is higher in patients with HCM compared to healthy individuals (5.28 [2.64; 13.96] and 0.84 [0.55; 1.23], respectively; p<0.001). Significantly higher levels of microRNA-21 were found in young patients aged from 19 to 45 years with the symptomatic course of HCM (36.76 [5.66; 42.22]) compared to patients with asymptomatic course <45 years of age (2.81 [1.45; 5.28]; p<0.002) and symptomatic patients ³45 years (3.88 [2.16; 8.63]; p<0.002).) The calculated risk of SCD was significantly higher in young symptomatic patients with HCM (6.01 [3.64; 9.67]) compared to patients with asymptomatic course <45 years (2.41 [1.21; 3.89]; p<0.001) and symptomatic patients ³45 years (2.56 [1.67; 4.41]; p<0.001).

Conclusion. The level of circulating microRNA-21 is significantly in patients with HCM compared to control group. The maximum level of circulating microRNA-21 was detected in patients with symptomatic course of HCM at the age of 45 years.

About the authors

A. Ya. Gudkova

Pavlov First Saint Petersburg State Medical University; Almazov National Medical Research Centre

Author for correspondence.
Email: alexagood-1954@mail.ru
ORCID iD: 0000-0003-0156-8821

д.м.н., проф. каф. факультетской терапии, зав. лаб. кардиомиопатий Института сердечно-сосудистых заболеваний; вед. науч. сотр. Института молекулярной биологии и генетики 

Russian Federation, Saint Petersburg

V. G. Davidova

Almazov National Medical Research Centre

Email: alexagood-1954@mail.ru
ORCID iD: 0000-0002-0233-5555

аспирант

Russian Federation, Saint Petersburg

T. G. Bezhanishvili

Pavlov First Saint Petersburg State Medical University

Email: alexagood-1954@mail.ru
ORCID iD: 0000-0002-3167-6340

клинический ординатор

Russian Federation, Saint Petersburg

S. A. Pyko

Saint Petersburg Electrotechnical University «LETI»

Email: alexagood-1954@mail.ru
ORCID iD: 0000-0001-6625-3770

к.т.н., доц.

Russian Federation, Saint Petersburg

M. I. Zarayskiy

Pavlov First Saint Petersburg State Medical University

Email: alexagood-1954@mail.ru
ORCID iD: 0000-0002-7605-4369

д.м.н., проф. каф. клинической лабораторной диагностики с курсом молекулярной медицины

Russian Federation, Saint Petersburg

References

  1. Лавров С.А., Кибанов М.В. Некодирующие РНК и структура хроматина. Успехи биологической химии. 2007;47:53-88 [Lavrov SA, Kibanov MV. Non-coding RNA and chromatin structure. Uspekhi biologicheskoj himii. 2007;47:53-88 (In Russ.)].
  2. Крокер Дж. Районы ядрышкового организатора и фибриллярные центры. Молекулярная клиническая диагностика. Методы. 1999:261-79 [Crocker J. Nucleolar organizer region and fibrillar centers. Molekulyarnaya klinicheskaya diagnostika. Metody. 1999:261-79 (In Russ.)].
  3. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843-54. doi: 10.1016/0092-8674(93)90529-y
  4. Рогаев Е.И., Григоренко А.П., Боринская С.А., Исламгулов Д.В. МикроРНК человека в норме и патологии. Молекулярная биология. 2008;42(5):751-7 [Rogaev EI, Grigorenko AP, Borinskaya SA, Islamgulov DV. Human microRNA in norm and pathology. Molecular Biology. 2008;42(5):751-7 (In Russ.)]. doi: 10.1134/S002689330805004X
  5. Ha M, Kim V. Regulation of microRNA biogenesis. Nature Rev Mol Cell Biol. 2014;15(8):509-24. doi: 10.1038/nrm3838
  6. 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(10):997-1006. doi: 10.1038/cr.2008.282
  7. Yang L, Wang B, Zhou Q, et al. MicroRNA-21 prevents excessive inflammation and cardiac dysfunction after myocardial infarction through targeting KBTBD7. Cell Death Dis. 2018;9(7):769. doi: 10.1038/s41419-018-0805-5
  8. Thum T, Gross C, Fiedler J, et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase organizer in fibroblasts. Nature. 2008;456(7224):980-4. doi: 10.1038/nature07511
  9. Morrisey EE. The magic and mystery of miR-21. Clin Invest. 2010;120(11):3817-9. doi: 10.1172/JCI44596
  10. Cheng Y, Zhang C. MicroRNA-21 in cardiovascular disease. J Cardiovasc Transl Res. 2010 Jun;3(3):251-5. doi: 10.1007/s12265-010-9169-7
  11. Li X, Wei Y, Wang Z. MicroRNA-21 and hypertension. Hypertens Res. 2018 Sep;41(9):649-61. doi: 10.1038/s41440-018-0071-z
  12. Zhang J, Xing Q, Zhou X, et al. Circulating miRNA 21 is a promising biomarker for heart failure. Mol Med Rep. 2017 Nov;16(5):7766-74. doi: 10.3892/mmr.2017.7575
  13. Chuppa S, Liang M, Liu P, et al. MicroRNA-21 regulates peroxisome proliferator-activated receptor alpha, a molecular mechanism of cardiac pathology in Cardiorenal Syndrome Type 4. Kidney Int. 2018;93(2):375-89. doi: 10.1016/j.kint.2017.05.014
  14. Qin Y, Yu Y, Dong H, et al. MicroRNA 21 inhibits left ventricular remodeling in the early phase of rat model with ischemia-reperfusion injury by suppressing cell apoptosis. Int J Med Sci. 2012;9(6):413-23. doi: 10.7150/ijms.4514
  15. Matturri L, Milei J, Grana D, Lavezzi A. Characterization of myocardial hypertrophy by DNA content, PCNA expression and apoptotic index. Int J Cardiol. 2002;82(1):33-9.
  16. Гудкова А.Я. Клинико-морфологические сопоставления и механизмы гипертрофии при обструктивной гипертрофической кардиомиопатии. Дис. … д.м.н. СПб., 2006 [Gudkova AYa. Clinico-morphological comparisons and mechanisms of hypertrophy in obstructive hypertrophic cardiomyopathy. Dissertaciya. Saint Petersburg, 2006 (In Russ.)].
  17. Elliott PM, Anastasakis A, Borger MA, et al. ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy. ESC Eur Heart J. 2014;35(39):2733-79. doi: 10.1093/eurheartj/ehu284
  18. Roma-Rodrigues C, Raposo LR, Fernandes AR. MicroRNAs Based Therapy of Hypertrophic Cardiomyopathy: The Road Traveled So Far. BioMed Res Int. 2015. Article ID: 983290. doi: 10.1155/2015/983290
  19. Sartorio CL, Lazzeroni D, Bertoli G, Camici PG. Theranostic biomarkers in hypertrophic cardiomyopathy: insights in a long road ahead. Frontiers in Bioscience. 2017;22:1724-49. doi: 10.2741/4568
  20. Шипилова Т., Удрас А., Лаане П., Кайк Ю. Течение и исходы гипертрофической кардиомиопатии при 15-20-летнем наблюдении. Кардиология. 1996;1:42-6 [Shipilova T, Udras A, Laane P, Kajk Yu. The course and outcome of hypertrophic cardiomyopathy with 15-20 years of follow-up. Kardiologiya. 1996;1:42-6 (In Russ.)].
  21. Maron B, Piccininno M, Casey S, et al. Relation of extreme left ventricular hypertrophy to age in hypertrophic cardiomyopathy. Am J Cardiol. 2003;91(5):626-8.
  22. Roncarati R, Viviani Anselmi C, Losi MA, et al. Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2014;63(9):920-7. doi: 10.1016/j.jacc.2013.09.041
  23. Fang L, Ellims AH, Moore XL, et al. Circulating microRNAs as biomarkers for diffuse myocardial fibrosis in patients with hypertrophic cardiomyopathy. J Transl Med. 2015;13:314. doi: 10.1186/s12967-015-0672-0
  24. 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

Supplementary files

Supplementary Files
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1. JATS XML
2. Correlation of age and echocardiographic indices in the GCMP group: а - age and MFD (r = -0.56; p <0.001); b - age and VLWF (r = 0.67; p <0.001)

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