Skip to main content
Log in

miRNAs emerge as circulating biomarkers of post-myocardial infarction heart failure

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Heart failure (HF) is a clinical syndrome that involves structural changes in the heart, leading to a decrease in cardiac output, mainly caused by myocardial infarction (MI), which is the most common form of cardiovascular disease worldwide. Clinical evaluation remains the most accurate diagnostic method for ischemic HF, since the known biomarkers have high cost, are difficult to use for early diagnosis, and have low specificity. This often leads to late diagnosis since only ~ 25% symptoms of HF appear after MI. Studies suggest that small non-coding RNAs (miRNAs) play an important role in the regulation of this pathophysiological process and are, therefore, important targets in the discovery of non-invasive biomarkers for HF. Thus, the aim of this review was to identify circulating miRNAs (plasma, serum, and whole blood) described for post-MI HF patients. This review covered 19 experimental studies on humans, which investigated the relationship between circulating miRNAs and the development, monitoring, or prognosis of ischemic HF. This analysis was aimed at proposing potential targets for HF and the future application of miRNAs as HF biomarkers.

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. Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, Falk V, González-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GMC, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P (2016) 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Rev Española Cardiol (English Ed) 69:1167. https://doi.org/10.1016/j.rec.2016.11.005

    Article  Google Scholar 

  2. He X, Ji J, Wang T, Wang MB, Chen XL (2017) Upregulation of circulating miR-195-3p in heart failure. Cardiol 138:107–114. https://doi.org/10.1159/000476029

    Article  CAS  Google Scholar 

  3. Minicucci MF, Azevedo PS, Polegato BF, Paiva SAR, Zornoff LAM (2011) Heart failure after myocardial infarction: clinical implications and treatment. Clin Cardiol 34:410–414

    Article  Google Scholar 

  4. Gupta SK, Foinquinos A, Thum S, Remke J, Zimmer K, Bauters C, de Groote P, Boon RA, de Windt LJ, Preissl S, Hein L, Batkai S, Pinet F, Thum T (2016) Preclinical development of a MicroRNA-based therapy for elderly patients with myocardial infarction. J Am Coll Cardiol 68:1557–1571. https://doi.org/10.1016/j.jacc.2016.07.739

    Article  CAS  PubMed  Google Scholar 

  5. Schaub JA, Coca SG, Moledina DG, Gentry M, Testani JM, Parikh CR (2015) Amino-terminal pro B-type natriuretic peptide for diagnosis and prognosis in patients with renal dysfunction. A Systematic Review and Meta-Analysis JACC Hear Fail 3:977–989

    Article  Google Scholar 

  6. Heil B, Tang WHW (2015) Biomarkers: their potential in the diagnosis and treatment of heart failure. Cleve Clin J Med 82:S28–S35

    Article  Google Scholar 

  7. Kumarswamy R, Thum T (2013) Non-coding RNAs in cardiac remodeling and heart failure. Circ Res 113:676–689. https://doi.org/10.1161/CIRCRESAHA.113.300226

    Article  CAS  PubMed  Google Scholar 

  8. Romaine SPR, Tomaszewski M, Condorelli G, Samani NJ (2015) MicroRNAs in cardiovascular disease: an introduction for clinicians. Heart 101:921–928. https://doi.org/10.1136/heartjnl-2013-305402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006. https://doi.org/10.1038/cr.2008.282

    Article  CAS  PubMed  Google Scholar 

  10. Glinge C, Clauss S, Boddum K, Jabbari R, Jabbari J, Risgaard B, Tomsits P, Hildebrand B, Kääb S, Wakili R, Jespersen T, Tfelt-Hansen J (2017) Stability of circulating blood-based microRNAs-pre-analytic methodological considerations. PLoS One 12:1–16. https://doi.org/10.1371/journal.pone.0167969

    Article  CAS  Google Scholar 

  11. Wang J, Liew OW, Richards AM, Chen YT (2016) Overview of microRNAs in cardiac hypertrophy, fibrosis, and apoptosis. Int J Mol Sci 17:1–21. https://doi.org/10.3390/ijms17050749

    Article  CAS  Google Scholar 

  12. Sun X-Q, Abbate A, Bogaard H-J (2017) Role of cardiac inflammation in right ventricular failure. Cardiovasc Res 113:1441–1452. https://doi.org/10.1093/cvr/cvx159

    Article  CAS  PubMed  Google Scholar 

  13. Boon RA, Dimmeler S (2015) MicroRNAs in myocardial infarction. Nat Rev Cardiol 12:135–142. https://doi.org/10.1161/ATVBAHA.112.300137

    Article  CAS  PubMed  Google Scholar 

  14. Corsten MF, Dennert R, Jochems S, Kuznetsova T, Devaux Y, Hofstra L, Wagner DR, Staessen JA, Heymans S, Schroen B (2010) Circulating MicroRNA-208b and MicroRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet 3:499–506. https://doi.org/10.1161/CIRCGENETICS.110.957415

    Article  PubMed  Google Scholar 

  15. Gelzinis TA (2014) New insights into diastolic dysfunction and heart failure with preserved ejection fraction. Semin Cardiothorac Vasc Anesth 18:208–217. https://doi.org/10.1177/1089253213510748

    Article  PubMed  Google Scholar 

  16. Gidlöf O, Smith JG, Miyazu K, Gilje P, Spencer A, Blomquist S, Erlinge D (2013) Circulating cardio-enriched microRNAs are associated with long-term prognosis following myocardial infarction. BMC Cardiovasc Disord 13(12). https://doi.org/10.1186/1471-2261-13-12

  17. Lv P, Zhou M, He J, Meng W, Ma X, Dong S, Meng X, Zhao X, Wang X, He F (2014) Circulating miR-208b and miR-34a are associated with left ventricular remodeling after acute myocardial infarction. Int J Mol Sci 15:5774–5788. https://doi.org/10.3390/ijms15045774

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhang R, Niu H, Ban T, Xu L, Li Y, Wang N, Sun L, Ai J, Yang B (2012) Elevated plasma microRNA-1 predicts heart failure after acute myocardial infarction. Int J Cardiol 166:259–260. https://doi.org/10.1016/j.ijcard.2012.09.108

    Article  PubMed  Google Scholar 

  19. He F, Lv P, Zhao X, Wang X, Ma X, Meng W, Meng X, Dong S (2014) Predictive value of circulating miR-328 and miR-134 for acute myocardial infarction. Mol Cell Biochem 394:137–144. https://doi.org/10.1007/s11010-014-2089-0

    Article  CAS  PubMed  Google Scholar 

  20. Pilbrow AP, Cordeddu L, Cameron VA, Frampton CM, Troughton RW, Doughty RN, Whalley GA, Ellis CJ, Yandle TG, Richards AM, Foo RSY (2014) Circulating miR-323-3p and miR-652: candidate markers for the presence and progression of acute coronary syndromes. Int J Cardiol 176:375–385. https://doi.org/10.1016/j.ijcard.2014.07.068

    Article  PubMed  Google Scholar 

  21. Liang J, Bai S, Su L et al (2015) A subset of circulating microRNAs is expressed differently in patients with myocardial infarction. Mol Med Rep 12:243–247. https://doi.org/10.3892/mmr.2015.3422

    Article  CAS  PubMed  Google Scholar 

  22. Fukushima Y, Nakanishi M, Nonogi H, Goto Y, Iwai N (2011) Assessment of plasma miRNAs in congestive heart failure. Circ J 75:336–340. https://doi.org/10.1253/circj.CJ-10-0457

    Article  CAS  Google Scholar 

  23. Bauters C, Kumarswamy R, Holzmann A, Bretthauer J, Anker SD, Pinet F, Thum T (2013) Circulating miR-133a and miR-423-5p fail as biomarkers for left ventricular remodeling after myocardial infarction. Int J Cardiol 168:1837–1840. https://doi.org/10.1016/j.ijcard.2012.12.074

    Article  PubMed  Google Scholar 

  24. Dubois-Deruy E, Cuvelliez M, Fiedler J, Charrier H, Mulder P, Hebbar E, Pfanne A, Beseme O, Chwastyniak M, Amouyel P, Richard V, Bauters C, Thum T, Pinet F (2017) MicroRNAs regulating superoxide dismutase 2 are new circulating biomarkers of heart failure. Sci Rep 7:1–10. https://doi.org/10.1038/s41598-017-15011-6

    Article  CAS  Google Scholar 

  25. Zhang M, Cheng Y-J, Sara J et al (2017) Circulating MicroRNA-145 is associated with acute myocardial infarction and heart failure. Chin Med J 130:51–56. https://doi.org/10.4103/0366-6999.196573

    Article  PubMed  PubMed Central  Google Scholar 

  26. MacIejak A, Kostarska-Srokosz E, Gierlak W et al (2018) Circulating MIR-30a-5p as a prognostic biomarker of left ventricular dysfunction after acute myocardial infarction. Sci Rep 8:1–11. https://doi.org/10.1038/s41598-018-28118-1

    Article  CAS  Google Scholar 

  27. de Gonzalo-Calvo D, Cediel G, Bär C, et al (2018) Circulating miR-1254 predicts ventricular remodeling in patients with ST-segment-elevation myocardial infarction: a cardiovascular magnetic resonance study. Sci Rep 8:1–9. https://doi.org/10.1038/s41598-018-33491-y

  28. Eitel I, Adams V, Dieterich P, Fuernau G, de Waha S, Desch S, Schuler G, Thiele H (2012) Relation of circulating MicroRNA-133a concentrations with myocardial damage and clinical prognosis in ST-elevation myocardial infarction. Am Heart J 164:706–714. https://doi.org/10.1016/j.ahj.2012.08.004

    Article  CAS  PubMed  Google Scholar 

  29. Matsumoto S, Sakata Y, Suna S, Nakatani D, Usami M, Hara M, Kitamura T, Hamasaki T, Nanto S, Kawahara Y, Komuro I (2013) Circulating p53-responsive MicroRNAs are predictive indicators of heart failure after acute myocardial infarction. Circ Res 113:322–326. https://doi.org/10.1161/CIRCRESAHA.113.301209

    Article  CAS  PubMed  Google Scholar 

  30. Dong Y-M, Liu X-X, Wei G-Q, da YN, Cha L, Ma CS (2015) Prediction of long-term outcome after acute myocardial infarction using circulating miR-145. Scand J Clin Lab Invest 75:85–91. https://doi.org/10.3109/00365513.2014.981855

    Article  CAS  PubMed  Google Scholar 

  31. Klenke S, Eul S, Peters J, Neumann T, Adamzik M, Frey UH (2018) Circulating miR-192 is a prognostic marker in patients with ischemic cardiomyopathy. Futur Cardiol 14:283–289. https://doi.org/10.2217/fca-2017-0108

    Article  CAS  Google Scholar 

  32. Wang A, Kwee LC, Grass E, Neely ML, Gregory SG, Fox KAA, Armstrong PW, White HD, Ohman EM, Roe MT, Shah SH, Chan MY (2017) Whole blood sequencing reveals circulating microRNA associations with high-risk traits in non-ST-segment elevation acute coronary syndrome. Atherosclerosis 261:19–25. https://doi.org/10.1016/j.atherosclerosis.2017.03.041

    Article  CAS  PubMed  Google Scholar 

  33. Shah R, Tanriverdi K, Levy D, Larson M, Gerstein M, Mick E, Rozowsky J, Kitchen R, Murthy V, Mikalev E, Freedman JE (2016) Discordant expression of circulating microRNA from cellular and extracellular sources. PLoS One 11:1–8. https://doi.org/10.1371/journal.pone.0153691

    Article  CAS  Google Scholar 

  34. Blondal T, Jensby Nielsen S, Baker A, Andreasen D, Mouritzen P, Wrang Teilum M, Dahlsveen IK (2013) Assessing sample and miRNA profile quality in serum and plasma or other biofluids. Methods 59:164–169. https://doi.org/10.1016/j.ymeth.2012.09.015

    Article  CAS  Google Scholar 

  35. Jiang Q, Wang Y, Hao Y, Juan L, Teng M, Zhang X, Li M, Wang G, Liu Y (2009) miR2Disease: a manually curated database for microRNA deregulation in human disease. Nucleic Acids Res 37:D98–D104. https://doi.org/10.1093/nar/gkn714

    Article  CAS  PubMed  Google Scholar 

  36. 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:D1013–D1017. https://doi.org/10.1093/nar/gky1010

    Article  CAS  PubMed  Google Scholar 

  37. Tomasetti M, Re M, Monaco F, Gaetani S, Rubini C, Bertini A, Pasquini E, Bersaglieri C, Bracci M, Staffolani S, Colomba M, Gregorini A, Valentino M, Tagliabracci A, Bovenzi M, Neuzil J, Amati M, Santarelli L (2018) MiR-126 in intestinal-type sinonasal adenocarcinomas: exosomal transfer of MiR-126 promotes anti-tumour responses. BMC Cancer 18:896. https://doi.org/10.1186/s12885-018-4801-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Li Y, Tao Y, Gao S, Li P, Zheng JM, Zhang SE, Liang J, Zhang Y (2018) Cancer-associated fibroblasts contribute to oral cancer cells proliferation and metastasis via exosome-mediated paracrine miR-34a-5p. EBioMedicine 36:209–220. https://doi.org/10.1016/j.ebiom.2018.09.006

    Article  PubMed  PubMed Central  Google Scholar 

  39. Alavi-Moghaddam M, Chehrazi M, Alipoor SD, Mohammadi M, Baratloo A, Mahjoub MP, Movasaghi M, Garssen J, Adcock IM, Mortaz E (2018) A preliminary study of microrna-208b after acute myocardial infarction: impact on 6-month survival. Dis Markers 2018:1–7. https://doi.org/10.1155/2018/2410451

    Article  CAS  Google Scholar 

  40. Hoekstra M (2017) MicroRNA-499-5p: a therapeutic target in the context of cardiovascular disease. Ann Transl Med 4:539–539. https://doi.org/10.21037/atm.2016.11.61

    Article  CAS  Google Scholar 

  41. Silva AMG, Araújo JNG, Freitas RCC, Silbiger VN (2017) Circulating MicroRNAs as potential biomarkers of atrial fibrillation. Biomed Res Int 2017:1–7. https://doi.org/10.3389/fimmu.2017.00118

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Vivian Nogueira Silbiger.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cruz, M.S., da Silva, A.M.G., de Souza, K.S.C. et al. miRNAs emerge as circulating biomarkers of post-myocardial infarction heart failure. Heart Fail Rev 25, 321–329 (2020). https://doi.org/10.1007/s10741-019-09821-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-019-09821-1

Keywords

Navigation