Vol 5, No 4 (2020)
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Published online: 2020-12-10

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Increased plasma levels of hsa-miR-21-5p in patients with reduced left ventricle ejection fraction admitted urgently due to acute coronary syndrome

Michał Krzysztof Kowara123, Wiktor Paskal4, Agata Gondek4, Renata Główczyńska3, Karolina Rybak1, Maciej Kubik1, Paweł Włodarski4, Grzegorz Opolski3, Agnieszka Cudnoch-Jędrzejewska1
Medical Research Journal 2020;5(4):250-255.


Myocardial ischemia that occurs during acute coronary syndrome (ACS) induces a cascade of pathophysiological processes which might lead to left ventricle dysfunction reflected by decreased left ventricular ejection fraction (LVEF) in echocardiographic examination. The enzymes regulating extracellular matrix (ECM) like matrix metalloproteinase 9 (MMP-9) also take part in this process. The MMP-9 activity is under control of a microRNA particle miR-21, which down-regulates its inhibitors. The study has shown, that in ACS population (n = 26) patients with LVEF < 50% presented increased miR-21 relative expression levels comparing to patients with LVEF ≥50% (3,33 vs 1,64; p = 0,015). Moreover, a significant negative correlation between LVEF and miR-21 in this group of patients has also been presented.

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  1. Saleh M, Ambrose J. Understanding myocardial infarction. F1000Research. 2018; 7: 1378.
  2. Bob-Manuel T, Ifedili I, Reed G, et al. Non-ST Elevation Acute Coronary Syndromes: A Comprehensive Review. Curr Probl Cardiol. 2017; 42(9): 266–305.
  3. James TN. The variable morphological coexistence of apoptosis and necrosis in human myocardial infarction: significance for understanding its pathogenesis, clinical course, diagnosis and prognosis. Coron Artery Dis. 1998; 9(5): 291–307.
  4. Meybohm, P., , Assessment of left ventricular systolic function during acute myocardial ischemia: a comparison of transpulmonary thermodilution and transesophageal echocardiography. Minerva Anestesiol, 2011. 77(2): p. : 132–41.
  5. Grandmougin, D., , Development of a porcine beating-heart model of self-myocardial retroperfusion: evaluation of hemodynamic and cardiac responses to ischemia and clinical applications. J Cardiovasc Surg (Torino), 2018. 59(3): p. : 438–452.
  6. Frangogiannis NG. Pathophysiology of Myocardial Infarction. Compr Physiol. 2015; 5(4): 1841–1875.
  7. DeLeon-Pennell KY, Meschiari CA, Jung M, et al. Matrix Metalloproteinases in Myocardial Infarction and Heart Failure. Prog Mol Biol Transl Sci. 2017; 147: 75–100.
  8. DeLeon-Pennell K, Brás Ld, Iyer R, et al. P. gingivalis lipopolysaccharide intensifies inflammation post-myocardial infarction through matrix metalloproteinase-9. Journal of Molecular and Cellular Cardiology. 2014; 76: 218–226.
  9. Bartel D. MicroRNAs: Genomics, Biogenesis, Mechanism, and Function. Cell. 2004; 116(2): 281–297.
  10. Fan X, Wang E, Wang X, et al. MicroRNA-21 is a unique signature associated with coronary plaque instability in humans by regulating matrix metalloproteinase-9 via reversion-inducing cysteine-rich protein with Kazal motifs. Exp Mol Pathol. 2014; 96(2): 242–249.
  11. Dai J, Chen W, Lin Y, et al. Exposure to Concentrated Ambient Fine Particulate Matter Induces Vascular Endothelial Dysfunction via miR-21. Int J Biol Sci. 2017; 13(7): 868–877.
  12. Roffi M, Patrono C, Collet JP, et al. ESC Scientific Document Group . 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016; 37(3): 267–315.
  13. Steg PhG, James SK, Atar D, et al. Task Force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J. 2012; 33(20): 2569–2619.
  14. Zhou SS, Jin JP, Wang JQ, et al. miRNAS in cardiovascular diseases: potential biomarkers, therapeutic targets and challenges. Acta Pharmacol Sin. 2018; 39(7): 1073–1084.
  15. Schulte C, Barwari T, Joshi A, et al. Comparative Analysis of Circulating Noncoding RNAs Versus Protein Biomarkers in the Detection of Myocardial Injury. Circulation Research. 2019; 125(3): 328–340.
  16. Kwee LC, Neely ML, Grass E, et al. Associations of osteopontin and NT-proBNP with circulating miRNA levels in acute coronary syndrome. Physiol Genomics. 2019; 51(10): 506–515.
  17. Zhang J, Ma J, Long K, et al. Overexpression of Exosomal Cardioprotective miRNAs Mitigates Hypoxia-Induced H9c2 Cells Apoptosis. Int J Mol Sci. 2017; 18(4).
  18. Jazbutyte V, Thum T. MicroRNA-21: from cancer to cardiovascular disease. Curr Drug Targets. 2010; 11(8): 926–935.
  19. Darabi F, Aghaei M, Movahedian A, et al. The role of serum levels of microRNA-21 and matrix metalloproteinase-9 in patients with acute coronary syndrome. Mol Cell Biochem. 2016; 422(1-2): 51–60.
  20. Kowara, M., , Increased serum microRNA21 levels reflect cardiac necrosis rather than plaque vulnerability in patients with acute coronary syndrome: a pilot study. Kardiol Pol, 2019. 77(11): p. : 1074–1077.
  21. Liu X, Dong Y, Chen S, et al. Circulating MicroRNA-146a and MicroRNA-21 Predict Left Ventricular Remodeling after ST-Elevation Myocardial Infarction. Cardiology. 2015; 132(4): 233–241.
  22. Squire IB, Evans J, Ng LL, et al. Plasma MMP-9 and MMP-2 following acute myocardial infarction in man: correlation with echocardiographic and neurohumoral parameters of left ventricular dysfunction. J Card Fail. 2004; 10(4): 328–333.
  23. Marques F, Vizi D, Khammy O, et al. The transcardiac gradient of cardio-microRNAs in the failing heart. European Journal of Heart Failure. 2016; 18(8): 1000–1008.
  24. Cheng Y, Zhu P, Yang J, et al. Ischaemic preconditioning-regulated miR-21 protects heart against ischaemia/reperfusion injury via anti-apoptosis through its target PDCD4. Cardiovasc Res. 2010; 87(3): 431–439.
  25. Tu Y, Wan L, Fan Y, et al. Ischemic postconditioning-mediated miRNA-21 protects against cardiac ischemia/reperfusion injury via PTEN/Akt pathway. PLoS One. 2013; 8(10): e75872.
  26. Yin C, Salloum F, Kukreja R. A Novel Role of MicroRNA in Late Preconditioning. Circulation Research. 2009; 104(5): 572–575.
  27. Huang W, Tian SS, Hang PZ, et al. Combination of microRNA-21 and microRNA-146a Attenuates Cardiac Dysfunction and Apoptosis During Acute Myocardial Infarction in Mice. Mol Ther Nucleic Acids. 2016; 5: e296.
  28. Gu GL, Xu XL, Sun XT, et al. Cardioprotective Effect of MicroRNA-21 in Murine Myocardial Infarction. Cardiovascular Therapeutics. 2015; 33(3): 109–117.
  29. Bejerano T, Etzion S, Elyagon S, et al. Nanoparticle Delivery of miRNA-21 Mimic to Cardiac Macrophages Improves Myocardial Remodeling after Myocardial Infarction. Nano Lett. 2018; 18(9): 5885–5891.