Signature of Serum miR-199a/b in Coronary Artery Bypass Graft Surgery

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coronary artery, microRNA, diagnostic marker, ischemia, reperfusion


Objective: microRNAs (miRNAs) have important potential as biomarkers in the diagnosis and prognosis of ischemia/reperfusion (I/R) injury in coronary artery bypass grafting surgery (CABG). This study investigated the relationship between preoperative (preop) and postoperative (post-op) cardiac parameters and miRNA expressions in CABG.

Methods: We analyzed a total of 94 individuals (CABG, n= 46 and healthy control, n=48). Quantitative real-time polymerase chain reaction (qRT) was performed to determine plasma miRNA expressions (miR-21, miR-181a, miR-199a, miR-199b, and miR-320a-5p) in triplicates: before surgery, 1 hour after surgery, and 24 hours after surgery. The target genes and pathways of miRNA were determined using bioinformatic analysis. The biomarker potentials of miRNAs were evaluated with receiver operating characteristic (ROC) curve analysis.

Results: All miRNAs were significantly downregulated (p < 0.05). Troponin I, LVEF, CPK, and CK-MB were found to be statistically significant for operation groups (p < 0.05). miRNA expressions and cardiac markers were associated with troponin I and/or CK-MB. In ROC analyses, miR-199a was a good diagnostic marker. CREBRF and ZNF704 genes may be a target for these miRNAs.

Conclusions: Downregulation of miR-199a has a regulatory role in ischemia/reperfusion. They may contribute to CABG pathology through these two genes involved in signaling cascades to turn on protein response and ion binding.


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Shahjehan RD, Bhutta BS. Coronary Artery Disease. StatPearls [Internet]. 2020.

Conti CR. Sudden Cardiac Death in Adult Patients with Stable Ischemic Heart Disease. Cardiovascular Innovations and Applications. 2019;3(3):317-9.

Guven G, Hilty MP, Ince C. Microcirculation: physiology, pathophysiology, and clinical application. Blood purification. 2020;49(1-2):143-50.

Belov Kirdajova D, Kriska J, Tureckova J, Anderova M. Ischemia-triggered glutamate excitotoxicity from the perspective of glial cells. Frontiers in cellular neuroscience. 2020;14:51.

Tsai C-F, Su H-H, Chen K-M, Liao J-M, Yao Y-T, Chen Y-H, etmal. Paeonol protects against myocardial ischemia/reperfusion-induced injury by mediating apoptosis and autophagyncrosstalk. Frontiers in pharmacology. 2020;11:2228.

Chaitra K, Ulaganathan K, James A, Ananthapur V, Nallari P. miRNA regulation during cardiac development and remodeling in cardiomyopathy. EXCLI journal. 2013;12:980.

Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. methods. 2001;25(4):402-8.

Chen Y, Wang X. miRDB: an online database for prediction of functional microRNA targets. Nucleic acids research. 2020;48(D1):D127-D31.

Karagkouni D, Paraskevopoulou MD, Chatzopoulos S, Vlachos IS, Tastsoglou S, Kanellos I, et al. DIANA-TarBase v8: a decade-long collection of experimentally supported miRNA-gene interactions. Nucleic acids research. 2018;46(D1):D239-D45.

Agarwal V, Bell GW, Nam J-W, Bartel DP. Predicting effective microRNA target sites in mammalian mRNAs. elife. 2015;4:e05005.

Friedman RC, Farh KK-H, Burge CB, Bartel DP. Most mammalian mRNAs are conserved targets of microRNAs. Genome research. 2009;19(1):92-105.

Bhattacharya A, Cui Y. miR2GO: comparative functional analysis for microRNAs. Bioinformatics. 2015;31(14):2403-5.

Fabregat A, Korninger F, Viteri G, Sidiropoulos K, Marin-Garcia P, Ping P, et al. Reactome graph database: Efficient access to complex pathway data. PLoS computational biology. 2018;14(1):e1005968.

Fabregat A, Sidiropoulos K, Viteri G, Marin-Garcia P, Ping P, Stein L, et al. Reactome diagram viewer: data structures and strategies to boost performance. Bioinformatics. 2018;34(7):1208-14.

Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic acids research. 2019;47(D1):D607-D13.

Corp I. IBM SPSS statistics for windows, version 22.0. Armonk, NY: IBM Corp. 2013. 17- Mayr B, Niebauer J, Breitenbach-Koller H. Circulating miRNAs as predictors for morbidity and mortality in coronary artery disease. Molecular biology reports. 2019;46(5):5661-5.

Dong S, Cheng Y, Yang J, Li J, Liu X, Wang X, et al. MicroRNA expression signature and the role of microRNA-21 in the early phase of acute myocardial infarction. Journal of Biological Chemistry. 2009;284(43):29514-25.

Zhu J, Yao K, Wang Q, Guo J, Shi H, Ma L, et al. Circulating miR-181a as a potential novel biomarker for diagnosis of acute myocardial infarction. Cellular Physiology and Biochemistry. 2016;40(6):1591-602.

Vegter EL, Ovchinnikova ES, van Veldhuisen DJ, Jaarsma T, Berezikov E, van der Meer P, et al. Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations. Clinical Research in Cardiology. 2017;106(8):598-609.

Yamac AH, Huyut MA, Yilmaz E, Celikkale I, Bacaksiz A, Demir Y, et al. MicroRNA 199a is downregulated in patients after coronary artery bypass graft surgery and is associated with increased levels of sirtuin 1 (SIRT 1) protein and major adverse cardiovascular events at 3-year follow-up. Medical science monitor: international medical journal of experimental and clinical research. 2018;24:6245.

Ren X-P, Wu J, Wang X, Sartor MA, Qian J, Jones K, et al. Clinical perspective. Circulation. 2009;119(17):2357-66.

Tülay Aydın P, Göz M, Kankılıç N, Aydın MS, Koyuncu İ. Micro‐RNA gene expressions during cardiopulmonary bypass. Journal of Cardiac Surgery. 2021;36(3):921-7.




How to Cite

Kandilli, E., Görücü Yılmaz, Şenay, Yardımcı, M., Nacak, M., & Benlier, N. (2023). Signature of Serum miR-199a/b in Coronary Artery Bypass Graft Surgery. European Journal of Therapeutics, 29(1), 1–9.



Original Articles