Vol 31, No 1 (2024)
Original Article
Published online: 2022-10-04

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Expression of miR-223 to predict outcomes after transcatheter aortic valve implantation

Ceren Eyileten1, Alicja Skrobucha2, Miłosz Starczyński2, Maria Boszko2, Joanna Jarosz-Popek1, Alex Fitas1, Krzysztof J. Filipiak3, Janusz Kochman2, Zenon Huczek2, Bartosz Rymuza2, Radosław Wilimski4, Mariusz Kuśmierczyk4, Jolanta M. Siller-Matula15, Marek Postula1, Aleksandra Gąsecka2
Pubmed: 36200549
Cardiol J 2024;31(1):111-123.

Abstract

Background: Transcatheter aortic valve implantation (TAVI) is an established treatment for aortic stenosis (AS) in patients at increased surgical risk. Up to 29% of patients annually experience major adverse cardiac and cerebrovascular events (MACCE) after TAVI. MicroRNAs (miRNA) are currently widely investigated as novel cardiovascular biomarkers. The aim of this study was to determine the influence of TAVI on the expressions of selected miRNAs associated with platelet function (miR-125a-5p, miR-125b and miR-223), and evaluate the predictive value of these miRNAs for MACCE in 65 patients undergoing TAVI.

Methods: Venous blood samples for miRNA expression analysis were collected 1 day before TAVI and at hospital discharge. The expression of miR-223, miR-125a-5p, miR-125b was evaluated in platelet-depleted plasma.

Results: The expression of miR-223 and miR-125b increased after TAVI, compared to the measurement before (p = 0.020, p = 0.003, respectively). Among 63 patients discharged from the hospital, 18 patients experienced MACCE (29%) during the median 15 months of observation. Baseline low miR-223 expression was a predictor of MACCE in univariate Cox regression analysis (hazard ratio [HR]: 2.71, 95% confidence interval [CI]: 1.04–7.01; p = 0.041). After inclusion of covariates, age, gender (male), New York Heart Association class and diabetes into the multivariate Cox regression model, miR-223 did not reach statistical significance (HR: 2.56, 95% CI: 0.79–8.33; p = 0.118).

Conclusions: To conclude, miR-223 might improve risk stratification after TAVI. Further studies are required to confirm the clinical applicability of this promising biomarker.

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References

  1. Baumgartner H, Falk V, Bax J, et al. 2017 ESC/EACTS Guidelines for the Management of Valvular Heart Disease. Rev Esp Cardiol. 2018; 71(2): 110.
  2. Chakos A, Wilson-Smith A, Arora S, et al. Long term outcomes of transcatheter aortic valve implantation (TAVI): a systematic review of 5-year survival and beyond. Ann Cardiothorac Surg. 2017; 6(5): 432–443.
  3. Amabile N, Ramadan R, Ghostine S, et al. Early and mid-term cardiovascular outcomes following TAVI: impact of pre-procedural transvalvular gradient. Int J Cardiol. 2013; 167(3): 687–692.
  4. Eftychiou C, Eteocleous N, Zittis I, et al. Outcomes of transfemoral transcatheter aortic valve implantation (TAVI) and predictors of thirty-day major adverse cardiovascular events (MACE) and one-year mortality. Hellenic J Cardiol. 2021; 62(1): 57–64.
  5. O'Sullivan CJ, Stortecky S, Heg D, et al. Impact of B-type natriuretic peptide on short-term clinical outcomes following transcatheter aortic valve implantation. EuroIntervention. 2015; 10(10): e1–e8.
  6. Ryan N, Nombela-Franco L, Jiménez-Quevedo P, et al. The value of the SYNTAX Score II in predicting clinical outcomes in patients undergoing transcatheter aortic valve implantation. Rev Esp Cardiol (Engl Ed). 2018; 71(8): 628–637.
  7. Bouchareb R, Boulanger MC, Tastet L, et al. Activated platelets promote an osteogenic programme and the progression of calcific aortic valve stenosis. Eur Heart J. 2019; 40(17): 1362–1373.
  8. Komosa A, Perek B, Rzymski P, et al. Platelet function in patients undergoing surgical and transcatheter aortic valve replacement: a comparative study. Kardiol Pol. 2021; 79(5): 554–561.
  9. Klimczak D, Pączek L, Jażdżewski K, et al. MicroRNAs: powerful regulators and potential diagnostic tools in cardiovascular disease. Kardiol Pol. 2015; 73(1): 1–6.
  10. Czajka P, Fitas A, Jakubik D, et al. MicroRNA as potential biomarkers of platelet function on antiplatelet therapy: a review. Front Physiol. 2021; 12: 652579.
  11. Pordzik J, Eyileten-Postuła C, Jakubik D, et al. MiR-126 is an independent predictor of long-term all-cause mortality in patients with type 2 diabetes mellitus. J Clin Med. 2021; 10(11).
  12. Pordzik J, Jakubik D, Jarosz-Popek J, et al. Significance of circulating microRNAs in diabetes mellitus type 2 and platelet reactivity: bioinformatic analysis and review. Cardiovasc Diabetol. 2019; 18(1): 113.
  13. Eyileten C, Wicik Z, Keshwani D, et al. Alteration of circulating platelet-related and diabetes-related microRNAs in individuals with type 2 diabetes mellitus: a stepwise hypoglycaemic clamp study. Cardiovasc Diabetol. 2022; 21(1): 79.
  14. Wicik Z, Czajka P, Eyileten C, et al. The role of miRNAs in regulation of platelet activity and related diseases: a bioinformatic analysis. Platelets. 2022; 33(7): 1052–1064.
  15. Schulte C, Molz S, Appelbaum S, et al. miRNA-197 and miRNA-223 predict cardiovascular death in a cohort of patients with symptomatic coronary artery disease. PLoS One. 2015; 10(12): e0145930.
  16. Eyileten C, Wicik Z, De Rosa S, et al. MicroRNAs as diagnostic and prognostic biomarkers in ischemic stroke: a comprehensive review and bioinformatic analysis. Cells. 2018; 7(12).
  17. Bhatlekar S, Manne BK, Basak I, et al. miR-125a-5p regulates megakaryocyte proplatelet formation via the actin-bundling protein L-plastin. Blood. 2020; 136(15): 1760–1772.
  18. Qu M, Fang F, Zou X, et al. miR-125b modulates megakaryocyte maturation by targeting the cell-cycle inhibitor p19. Cell Death Dis. 2016; 7(10): e2430.
  19. Laffont B, Corduan A, Plé H, et al. Activated platelets can deliver mRNA regulatory Ago2•microRNA complexes to endothelial cells via microparticles. Blood. 2013; 122(2): 253–261.
  20. De Rosa S, Gareri C, Iaconetti C, et al. 4796Modulation of exosomal microRNA in patients with severe aortic stenosis after transcatheter aortic valve implantation (TAVI). Eur Heart J. 2017; 38(suppl_1).
  21. Takahashi K, Satoh M, Takahashi Y, et al. Dysregulation of ossification-related miRNAs in circulating osteogenic progenitor cells obtained from patients with aortic stenosis. Clin Sci (Lond). 2016; 130(13): 1115–1124.
  22. Kleeberger JA, Neuser J, de Gonzalo-Calvo D, et al. microRNA-206 correlates with left ventricular function after transcatheter aortic valve implantation. Am J Physiol Heart Circ Physiol. 2017; 313(6): H1261–H1266.
  23. Iacopo F, Lorenzo C, Calogero E, et al. Review in translational cardiology: micrornas and myocardial fibrosis in aortic valve stenosis, a deep insight on left ventricular remodeling. J Cardiovasc Echogr. 2016; 26(4): 109–114.
  24. Varrone F, Gargano B, Carullo P, et al. The circulating level of FABP3 is an indirect biomarker of microRNA-1. J Am Coll Cardiol. 2013; 61(1): 88–95.
  25. Zareba L, Fitas A, Wolska M, et al. MicroRNAs and long noncoding rnas in coronary artery disease: new and potential therapeutic targets. Cardiol Clin. 2020; 38(4): 601–617.
  26. Pordzik J, Pisarz K, De Rosa S, et al. The potential role of platelet-related microRNAs in the development of cardiovascular events in high-risk populations, including diabetic patients: a review. Front Endocrinol (Lausanne). 2018; 9: 74.
  27. De Rosa S, La Bella S, Canino G, et al. Reciprocal modulation of Linc-223 and its ligand miR-125a on the basis of platelet function level. Eur Heart J. 2020; 41(Suppl_2).
  28. Wang H, Shi J, Li B, et al. MicroRNA expression signature in human calcific aortic valve disease. Biomed Res Int. 2017; 2017: 4820275.
  29. Goody PR, Hosen MR, Christmann D, et al. Aortic valve stenosis: from basic mechanisms to novel therapeutic targets. Arterioscler Thromb Vasc Biol. 2020; 40(4): 885–900.
  30. 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): 920–927.
  31. Baratchi S, Zaldivia MTK, Wallert M, et al. Transcatheter aortic valve implantation represents an anti-inflammatory therapy via reduction of shear stress-induced, piezo-1-mediated monocyte activation. Circulation. 2020; 142(11): 1092–1105.
  32. Chen T, Huang Z, Wang L, et al. MicroRNA-125a-5p partly regulates the inflammatory response, lipid uptake, and ORP9 expression in oxLDL-stimulated monocyte/macrophages. Cardiovasc Res. 2009; 83(1): 131–139.
  33. Fernández-Hernando C, Suárez Y. MicroRNAs in endothelial cell homeostasis and vascular disease. Curr Opin Hematol. 2018; 25(3): 227–236.
  34. Goettsch C, Rauner M, Pacyna N, et al. miR-125b regulates calcification of vascular smooth muscle cells. Am J Pathol. 2011; 179(4): 1594–1600.
  35. Fan JL, Zhu TT, Xue ZY, et al. lncRNA-XIST protects the hypoxia-induced cardiomyocyte injury through regulating the miR-125b-hexokianse 2 axis. In Vitro Cell Dev Biol Anim. 2020; 56(4): 349–357.
  36. Hueso M, De Ramon L, Navarro E, et al. Silencing of CD40 in vivo reduces progression of experimental atherogenesis through an NF-κB/miR-125b axis and reveals new potential mediators in the pathogenesis of atherosclerosis. Atherosclerosis. 2016; 255: 80–89.
  37. Katoh M. Cardio-miRNAs and onco-miRNAs: circulating miRNA-based diagnostics for non-cancerous and cancerous diseases. Front Cell Dev Biol. 2014; 2: 61.
  38. Wang X, Ha T, Zou J, et al. MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via targeting p53-mediated apoptotic signalling and TRAF6. Cardiovasc Res. 2014; 102(3): 385–395.
  39. Xiaochuan B, Qianfeng J, Min Xu, et al. RASSF1 promotes cardiomyocyte apoptosis after acute myocardial infarction and is regulated by miR-125b. J Cell Biochem. 2020; 121(1): 489–496.
  40. Ikeda S, Kong SW, Lu J, et al. Altered microRNA expression in human heart disease. Physiol Genomics. 2007; 31(3): 367–373.
  41. Shi R, Zhou X, Ji WJ, et al. The emerging role of miR-223 in platelet reactivity: implications in antiplatelet therapy. Biomed Res Int. 2015; 2015: 981841.
  42. Tan M, Yan HB, Li JN, et al. Thrombin stimulated platelet-derived exosomes inhibit platelet-derived growth factor receptor-beta expression in vascular smooth muscle cells. Cell Physiol Biochem. 2016; 38(6): 2348–2365.
  43. Li S, Chen H, Ren J, et al. MicroRNA-223 inhibits tissue factor expression in vascular endothelial cells. Atherosclerosis. 2014; 237(2): 514–520.
  44. Vegter EL, Ovchinnikova ES, van Veldhuisen DJ, et al. Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations. Clin Res Cardiol. 2017; 106(8): 598–609.
  45. Wang X, Gu H, Qin D, et al. Exosomal miR-223 contributes to mesenchymal stem cell-elicited cardioprotection in polymicrobial sepsis. Sci Rep. 2015; 5: 13721.
  46. Zhang XY, Wang XR, Xu DM, et al. HAMI 3379, a CysLT2 receptor antagonist, attenuates ischemia-like neuronal injury by inhibiting microglial activation. J Pharmacol Exp Ther. 2013; 346(2): 328–341.
  47. Zhao Y, Gan Y, Xu G, et al. Exosomes from MSCs overexpressing microRNA-223-3p attenuate cerebral ischemia through inhibiting microglial M1 polarization mediated inflammation. Life Sci. 2020; 260: 118403.
  48. Zhang L, Yang J, Guo M, et al. MiR-223-3p affects myocardial inflammation and apoptosis following myocardial infarction via targeting FBXW7. J Thorac Dis. 2022; 14(4): 1146–1156.
  49. Liu X, Deng Y, Xu Y, et al. MicroRNA-223 protects neonatal rat cardiomyocytes and H9c2 cells from hypoxia-induced apoptosis and excessive autophagy via the Akt/mTOR pathway by targeting PARP-1. J Mol Cell Cardiol. 2018; 118: 133–146.
  50. Chen Y, Song Y, Huang J, et al. Increased circulating exosomal miRNA-223 is associated with acute ischemic stroke. Front Neurol. 2017; 8: 57.
  51. Shen NN, Zhang C, Li Z, et al. MicroRNA expression signatures of atrial fibrillation: the critical systematic review and bioinformatics analysis. Exp Biol Med (Maywood). 2020; 245(1): 42–53.
  52. Hromadka M, Motovska Z, Hlinomaz O, et al. MiR-126-3p and MIR-223-3p as biomarkers for prediction of thrombotic risk in patients with acute myocardial infarction and primary angioplasty. J Pers Med. 2021; 11(6).
  53. Tiedt S, Prestel M, Malik R, et al. RNA-Seq identifies circulating miR-125a-5p, miR-125b-5p, and miR-143-3p as potential biomarkers for acute ischemic stroke. Circ Res. 2017; 121(8): 970–980.
  54. Bogyi M, Schernthaner RE, Loewe C, et al. Subclinical leaflet thrombosis after transcatheter aortic valve replacement: a meta-analysis. JACC Cardiovasc Interv. 2021; 14(24): 2643–2656.
  55. Correia de Sousa M, Gjorgjieva M, Dolicka D, et al. Deciphering miRNAs' action through miRNA editing. Int J Mol Sci. 2019; 20(24).
  56. Chyrchel B, Totoń-Żurańska J, Kruszelnicka O, et al. Association of plasma miR-223 and platelet reactivity in patients with coronary artery disease on dual antiplatelet therapy: a preliminary report. Platelets. 2015; 26(6): 593–597.
  57. Taïbi F, Metzinger-Le Meuth V, Massy ZA, et al. miR-223: an inflammatory oncomiR enters the cardiovascular field. Biochim Biophys Acta. 2014; 1842(7): 1001–1009.