Analysis of circulating miRNA levels in coronary heart disease patients with varying degrees of cardiovascular complications risk. correlations with the MSCT-CA data

Cover Page
  • Authors: Rozhkov A.N.1, Shchekochikhin D.Y.1, Baulina N.М.2, Matveeva N.A.2, Favorova O.O.2, Akselrod A.S.1, Tebenkova E.S.1, Gognieva D.G.1, Kopylov P.Y.1
  • Affiliations:
    1. I.M. Sechenov First Moscow State Medical University (Sechenov University)
    2. National Medical Research Center of Cardiology
  • Issue: Vol 75, No 4 (2020)
  • Pages: 283-291
  • Section: MOLECULAR MEDICINE AND GENETICS: CURRENT ISSUES
  • URL: https://vestnikramn.spr-journal.ru/jour/article/view/1325
  • DOI: https://doi.org/10.15690/vramn1325
  • Cite item
Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract


Rationale. Cardiovascular diseases remain the leading cause of human death in the world. Studying the role of regulatory non-coding RNAs, which include short single-stranded miRNA molecules, allows a more detailed understanding of the pathological processes underlying the progression of atherosclerosis.

Objective — to compare the levels of circulating miRNAs in patients with coronary heart disease, confirmed by multislice computed tomography-coronarography (MSCT-CA), with risks of cardiovascular complications and clinical and demographic characteristics. To compare the profiles of circulating miRNAs in groups of patients with stable and unstable atherosclerotic plaques.

Methods. MicroRNA levels in the plasma of peripheral blood of patients with coronary heart disease were determined using the miScript miRNA PCR Array MIHS-105Z kit (Qiagen). The significance of differences in miRNA levels between the compared groups was determined using the Mann–Whitney U-test. The correlations of the levels of circulating miRNAs with clinical and demographic parameters were evaluated using the Spearman correlation coefficient. Risk assessment of cardiovascular complications in these patients was carried out using validated scales (ACC/AHA, Framinghm, SCORE, MESA). Atherosclerotic plaque stability was evaluated using MSCT-CA.

Results. The study showed a significant (p < 0.05) decrease in miR-16, miR-211, miR-195 miRNA levels in the plasma of patients with coronary heart disease, which correlated with an increase in cardiac vascular risk (CVR) according to ACC/AHA, Framingham and MESA. When comparing groups of patients with stable and unstable atherosclerotic plaques, the latter revealed an increase in the level of let-7b-5p circulating microRNA (p < 0.05).

 Conclusion. Significant associations of the three studied microRNAs with the estimated risk of CVR were identified. It is important to find circulating let-7b-5p in a group of patients with unstable atherosclerotic plaques. Correlations were established between the levels of circulating microRNAs and clinical and demographic characteristics of patients. The study shows the involvement of some microRNAs in the regulation of atherosclerosis.


Full Text

Restricted Access

About the authors

Andrey N. Rozhkov

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: arozhkov@outlook.com
ORCID iD: 0000-0002-2735-076X

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD

Dmitriy Yu. Shchekochikhin

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: agishm@list.ru
ORCID iD: 0000-0002-8209-2791
SPIN-code: 3753-6915

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD, PhD, Associate Professor

Natalia М. Baulina

National Medical Research Center of Cardiology

Email: tati.90@mail.ru
ORCID iD: 0000-0001-8767-2958
SPIN-code: 4704-0104

Russian Federation, 15a, 3rd Cherepkovskaya street, Moscow, 121552

MD, PhD in Biology, Research Associate

Natalia A. Matveeva

National Medical Research Center of Cardiology

Email: natalijamat@rambler.ru
ORCID iD: 0000-0002-4369-2882
SPIN-code: 8760-4002

Russian Federation, 15a, 3rd Cherepkovskaya street, Moscow, 121552

PhD in Biology, Research Associate

Olga O. Favorova

National Medical Research Center of Cardiology

Email: olga_favorova@mail.ru
ORCID iD: 0000-0002-5271-6698
SPIN-code: 8500-7456

Russian Federation, 15a, 3rd Cherepkovskaya street, Moscow, 121552

PhD in Biology, Proffessor

Anna S. Akselrod

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: 7402898@mail.ru
ORCID iD: 0000-0003-3417-794X
SPIN-code: 4566-7759

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

д.м.н., профессор

Ekaterina S. Tebenkova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: flor670@yandex.ru
ORCID iD: 0000-0003-4991-675X

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD, PhD, Associate Professor

Daria G. Gognieva

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: dashkagog@mail.ru
ORCID iD: 0000-0002-0451-2009
SPIN-code: 4011-5405

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD, PhD Student

Philipp Yu. Kopylov

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: fjk@inbox.ru
ORCID iD: 0000-0001-5124-6383
SPIN-code: 8287-6897

Russian Federation, 8-2, Trubetskaya street, Moscow, 119992

MD, PhD, Professor

References

  1. Гайсенок О.В., Рожков А.Н., Лишута А.С. Гиполипидемическая терапия в аспекте профилактики острых нарушений мозгового кровообращения: существующие стандарты, данные доказательной медицины и реальная практика // Рациональная фармакотерапия в кардиологии. — 2018. — № 14 (3). — С. 434–440. [Gaisenok OV, Rozhkov AN, Lishuta AS. Hypolipidemic therapy in stroke prevention: existing standards, evidence-based medicine data and real practice. Rational Pharmacotherapy in Cardiology. 2018;14(3):434–440. (In Russ.)] doi: 10.20996/1819-6446-2018-14-3-434-440.
  2. Libby P. Inflammation in atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology. 2012;32:2045–2051. doi: 10.1161/ATVBAHA.108.179705.
  3. Zhang X, Dong H, Tian Y. MicroRNA Detection and Pathological Functions: Introduction. In: Zhang X, Dong H, Tian Y. eds. MicroRNA Detection and Pathological Functions, 1–6. Berlin, Heidelberg: Springer Berlin Heidelberg; 2015.
  4. Wei Y, Schober A, Weber C, Pathogenic arterial remodeling: the good and bad of microRNAs. American Journal of Physiology. Heart and Circulatory Physiology. 2013;304:H1050–9. doi: 10.1152/ajpheart.00267.2012.
  5. Siddeek B, Mauduit C, Yzydorczyk C, Benahmed M, Simeoni U. At the heart of programming: the role of micro-RNAs. Journal of Developmental Origins of Health and Disease. 2018;9(6):615–631. doi: 10.1017/S2040174418000387.
  6. Kim JS, Pak K, Goh TS, Jeong DC, Han ME, Kim J, Oh SO, Kim CD, Kim YH. Prognostic Value of MicroRNAs in Coronary Artery Diseases: a Meta-Analysis. Yonsei Medical Journal. 2018;59(4):495–500. doi: 10.3349/ymj.2018.59.4.495.
  7. Li Y-H, Lin G-M, Lai C-P, Lin C-L, Wang J-H. The “smoker’s paradox” in Asian versus non-Asian patients with percutaneous coronary intervention longer than 6 months follow-up: a collaborative meta-analysis with the ET-CHD registry. International Journal of Cardiology. 2013;168:4544–4548. doi: 10.1016/j.ijcard.2013.06.093.
  8. McManus DD, Rong J, Huan T, Lacey S, Tanriverdi K, Munson PJ, Larson MG, Joehanes R, Murthy V, Shah R, Freedman JE, Levy D. Messenger RNA and MicroRNA transcriptomic signatures of cardiometabolic risk factors. BMC Genomics. 2017;18:139. doi: 10.1186/s12864-017-3533-9.
  9. Zampetaki A, Willeit P, Tilling L, Drozdov I, Prokopi M, Renard J-M, Mayr A, Weger S, Schett G, Shah A, Boulanger CM, Willeit J, Chowienczyk PJ, Kiechl S, Mayr M. Prospective study on circulating MicroRNAs and risk of myocardial infarction. Journal of the American College of Cardiology. 2012;60:290–299. doi: 10.1016/j.jacc.2012.03.056.
  10. Keller T, Boeckel J-N, Groß S, Klotsche J, Palapies L, Leistner D, Pieper L, Stalla GK, Lehnert H, Silber S, Pittrow D, Maerz W, Dörr M, Wittchen H-U, Baumeister SE, Völker U, Felix SB, Dimmeler S, Zeiher AM. Improved risk stratification in prevention by use of a panel of selected circulating microRNAs. Scientific Reports. 2017;7:4511. doi: 10.1038/s41598-017-04040-w.
  11. Raitoharju E, Oksala N, Lehtimäki T. MicroRNAs in the atherosclerotic plaque. Clinical Chemistry. 2013;59:1708–1721. doi: 10.1373/clinchem.2013.204917.
  12. Веселова Т.Н., Терновой С.К. Выявление нестабильных бляшек в коронарных артериях с помощью мультиспиральной компьютерной томографии // Российский электронный журнал лучевой диагностики. — 2014. —№ 4. — С. 7–13. [Veselova TN, Ternovoy SK. MDCT in detection of unstable coronary plaques. REJR. 2014;4:7–13. (In Russ.)]
  13. Yoo SM, Lee HY, Jin KN, Chun EJ, Ann FA, White CS. Current Concepts of Vulnerable Plaque on Coronary CT Angiography. Cardiovascular Imaging Asia. 2017;1:4. doi: 10.22468/cvia.2016.00073.
  14. Van Rosendael AR, Narula J, Lin FY, van den Hoogen IJ, Gianni U, Hussein A, Alawamlh O, Dunham PC, Peña JM, Lee S-E, Andreini D, Cademartiri F, Chinnaiyan K, Chow BJW, Conte E, Cury RC, Feuchtner G, Hadamitzky M, Kim Y-J, Leipsic J, Maffei E, Marques H, de Araújo Gonçalves P, Plank F, Pontone G, Raff GL, Villines TC, Weirich HG, Al’Aref SJ, Baskaran L, Cho I, Danad I, Han D, Heo R, Lee JH, Rivzi A, Stuijfzand WJ, Gransar H, Lu Y, Sung JM, Park H-B, Samady H, Stone PH, Virmani R, Budoff MJ, Berman DS, Chang H-J, Bax JJ, Min JK, Shaw LJ. Association of High-Density Calcified 1K Plaque with Risk of Acute Coronary Syndrome. JAMA Cardiology. 2020;5(3):282. doi: 10.1001/jamacardio.2019.5315.
  15. Criqui MH, Denenberg JO, Ix JH, McClelland RL, Wassel CL, Rifkin DE, Carr JJ, Budoff MJ, Allison MA. Calcium density of coronary artery plaque and risk of incident cardiovascular events. JAMA. 2014;311:271–278. doi: 10.1001/jama.2013.282535.
  16. Stather PW, Sylvius N, Wild JB, Choke E, Sayers RD, Bown MJ. Differential microRNA expression profiles in peripheral arterial disease. Circulation. Cardiovascular Genetics. 2013;6:490–497. doi: 10.1161/CIRCGENETICS.111.000053.
  17. Liang X, Xu Z, Yuan M, Zhang Y, Zhao B, Wang J, Zhang A, Li G. MicroRNA-16 suppresses the activation of inflammatory macrophages in atherosclerosis by targeting PDCD4. International Journal of Molecular Medicine. 2016;37:967–975. doi: 10.3892/ijmm.2016.2497.
  18. O’Sullivan JF, Neylon A, McGorrian C, Blake GJ. MiRNA-93-5p and other miRNAs as predictors of coronary artery disease and STEMI. International Journal of Cardiology. 2016;224:310–316. doi: 10.1016/j.ijcard.2016.09.016.
  19. Choteau SA, Cuesta Torres LF, Barraclough JY, Elder AMM, Martínez GJ, Chen Fan WY, Shrestha S, Ong KL, Barter PJ, Celermajer DS, Rye K-A, Patel S, Tabet F. Transcoronary gradients of HDL-associated MicroRNAs in unstable coronary artery disease. International Journal of Cardiology. 2018;253:138–144. doi: 10.1016/j.ijcard.2017.09.190.
  20. De Rosa S, Fichtlscherer S, Lehmann R, Assmus B, Dimmeler S, Zeiher AM. Transcoronary concentration gradients of circulating microRNAs. Circulation. 2011;124:1936–1944. doi: 10.1161/CIRCULATIONAHA.111.037572.
  21. Marques FZ, Vizi D, Khammy O, Mariani JA, Kaye DM. The transcardiac gradient of cardio-microRNAs in the failing heart. European Journal of Heart Failure. 2016;18:1000–1008. doi: 10.1002/ejhf.517.
  22. Bras JP, Silva AM, Calin GA, Barbosa MA, Santos SG, Almeida MI. MiR-195 inhibits macrophages pro-inflammatory profile and impacts the crosstalk with smooth muscle cells. PloS One. 2017;12:e0188530. doi: 10.1371/journal.pone.0188530.
  23. Long G, Wang F, Duan Q, Yang S, Chen F, Gong W, Yang X, Wang Y, Chen C, Wang DW. Circulating miR-30a, miR-195 and let-7b associated with acute myocardial infarction. PloS One. 2012;7: e50926. doi: 10.1371/journal.pone.0050926.
  24. Jiang Y, Wang H-Y, Li Y, Guo S-H, Zhang L, Cai J-H, Cao H-M, Wang C-Y, Wang H, Liu L. Peripheral blood miRNAs as a biomarker for chronic cardiovascular diseases. Scientific Reports. 2014:4:5026. doi: 10.1038/srep05026.
  25. Chen J, Yang T, Yu H, Sun K, Shi Y, Song W, Bai Y, Wang X, Lou K, Song Y, Zhang Y, Hui R. A functional variant in the 3’-UTR of angiopoietin-1 might reduce stroke risk by interfering with the binding efficiency of microRNA 211. Human Molecular Genetics. 2019;19:2524–2533. doi: 10.1093/hmg/ddq131.
  26. Fujisawa T, Wang K, Niu X-L, Egginton S, Ahmad S, Hewett P, Kontos CD, Ahmed A. Angiopoietin-1 promotes atherosclerosis by increasing the proportion of circulating Gr1+ monocytes. Cardiovascular Research. 2017;113:81–89. doi: 10.1093/cvr/cvw223.
  27. Ou X, Gao J-H, He L-H, Yu X-H, Wang G, Zou J, Zhao Z-W, Zhang D-W, Zhou Z-J, Tang C-K. Angiopoietin-1 aggravates atherosclerosis by inhibiting cholesterol efflux and promoting inflammatory response. Biochimica et Biophysica Acta. Molecular and Cell Biology of Lipids. 2020;1865:158535. doi: 10.1016/j.bbalip.2019.158535.
  28. 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 ST, Guiry P, Jandeleit-Dahm KAM, Cooper ME, Godson C, Kantharidis P. Protective Effect of let-7 miRNA Family in Regulating Inflammation in Diabetes-Associated Atherosclerosis. Diabetes. 2017;66:2266–2277. doi: 10.2337/db16-1405.
  29. Parahuleva MS, Lipps C, Parviz B, Hölschermann H, Schieffer B, Schulz R, Euler G. MicroRNA expression profile of human advanced coronary atherosclerotic plaques. Scientific Reports. 2018;8:7823. doi: 10.1038/s41598-018-25690-4.
  30. Li S, Lee C, Song J, Lu C, Liu J, Cui Y, Liang H, Cao C, Zhang F, Chen H. Circulating microRNAs as potential biomarkers for coronary plaque rupture. Oncotarget. 2017;8:48145–48156. doi: 10.18632/oncotarget.18308.
  31. Bao M-H, Zhang Y-W, Lou X-Y, Cheng Y, Zhou H-H. Protective effects of let-7a and let-7b on oxidized low-density lipoprotein induced endothelial cell injuries. PloS One. 2014;9:e106540. doi: 10.1371/journal.pone.0106540.
  32. Hulsmans M, Holvoet P. MicroRNA-containing microvesicles regulating inflammation in association with atherosclerotic disease. Cardiovascular Research. 2013;100:7–18. doi: 10.1093/cvr/cvt161.
  33. Cury RC, Abbara S, Achenbach S, Agatston A, Berman DS, Budoff MJ, et al. CAD-RADSTM Coronary Artery Disease – Reporting and Data System. An expert consensus document of the Society of Cardiovascular Computed Tomography (SCCT), the American College of Radiology (ACR) and the North American Society for Cardiovascular Imaging (NASCI). Endorsed by the American College of Cardiology. Journal of Cardiovascular Computed Tomography. 2016;10(4):269–281. doi: 10.1016/j.jcct.2016.04.005.

Supplementary files

Supplementary Files Action
1.
Figure: 1. Significant differences in miR-16 levels in patients at risk of CVC on the MESA scale less than and more than 10% over 10 years

View (79KB) Indexing metadata
2.
Figure: 2. Significant differences in miR-211 levels in patients with CVC risk according to the Framingham scale less than and more than 10% over 10 years

View (80KB) Indexing metadata
3.
Figure: 3. MiR-211 levels in patients at risk of CVC on the ACC / AHA scale less than and more than 10% over 10 years

View (79KB) Indexing metadata
4.
Figure: 4. Levels of miR-211 in patients with very low, low, moderate and high risks on the Framingham scale

View (78KB) Indexing metadata
5.
Figure: 5. Levels of miR-195 in patients with low, borderline, moderate and high risks on the MESA scale

View (70KB) Indexing metadata

Statistics

Views

Abstract - 849

PDF (Russian) - 1

Cited-By


PlumX

Dimensions



Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies