Circulating microRNA-126 in patients with ischemic heart disease with type 2 diabetes mellitus and its relationship with glucometabolic disorders

Authors

DOI:

https://doi.org/10.14739/2310-1210.2022.5.257413

Keywords:

coronary artery disease, type 2 diabetes mellitus, miсroRNA, blood glucose, insulin resistance

Abstract

The aim of the study was to investigate circulating microRNA-126-3p levels and its relationships with glucometabolic indices in patients with ischemic heart disease (IHD) and type 2 diabetes mellitus (Т2DM).

Materials and methods. The study included 68 patients with stable coronary artery disease (CAD) and T2DM, 25 CAD patients without diabetes and 18 healthy individuals as a control. MiRNA126-3p was determined in blood plasma by real time polymerase chain reaction. Small nuclear RNA U6 was used as an endogenous control.

Results. Circulating miRNA-126-3p levels in CAD patients both with T2DM (50.32 [19.54; 93.82]) and without diabetes (109.46 [49.52; 211.11]) were higher than in the controls (17.95 [13.74; 35.01]) (P = 0.018 and P < 0.001). But in patients with T2DM, miRNA126-3p level was decreased in comparison with patients without diabetes (P < 0.001).

In patients with T2DM, miRNA-126-3p displayed a significant negative correlation with blood glucose level (R = -0.259, P = 0.037) and was correlated negatively with glycosylated hemoglobin (R = -0.246, Р = 0.056) and insulin resistance index HOMA-IR (R = -0.229, P = 0.082) reaching boundary level of statistical significance. In diabetic patients, lower miRNA-126-3p level (the 1st tertile) was associated with a significant increase in blood glucose level and HOMA-IR in comparison with the 3rd tertile (P = 0.011 and P = 0.041).

According to the ROC-analysis, the decrease in miRNA-126-3p levels was significantly associated with the presence of T2DM in patients with САD: AUC was 0.734 (95 % CI: 0.631–0.822, P < 0.001).

Conclusions. Circulating miRNA-126-3p levels in CAD patients both with and without T2DM were increased compared to the controls, possibly due to compensatory mechanisms. However, in patients with T2DM, miRNA-126-3p expression was significantly lower than in patients without T2DM.

The lowest miRNA-126-3p level in CAD patients with T2DM was associated with the significant elevation of blood glucose level and the increase in insulin resistance. MiRNA-126-3p may serve as potential biomarker for predicting and early diagnosis of T2DM in patients with CAD.

 

Author Biographies

S. A. Serik, GI “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine”, Kharkiv

MD, PhD, DSc, Senior Researcher, Head of the Department of Ischemic Heart Disease, Metabolic and Cardiopulmonary Disorders

N. R. Mavrycheva, GI “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine”, Kharkiv

MD, Junior Researcher of the Department of Ischemic Heart Disease, Metabolic and Cardiopulmonary Disorders

T. M. Bondar, GI “L. T. Malaya Therapy National Institute of the National Academy of Medical Sciences of Ukraine”, Kharkiv

PhD, Senior Researcher of the Laboratory of Immuno-Biochemical and Molecular-Genetic Research

References

Tsao, C. W., Aday, A. W., Almarzooq, Z. I., Alonso, A., Beaton, A. Z., Bittencourt, M. S., Boehme, A. K., Buxton, A. E., Carson, A. P., Commodore-Mensah, Y., Elkind, M., Evenson, K. R., Eze-Nliam, C., Ferguson, J. F., Generoso, G., Ho, J. E., Kalani, R., Khan, S. S., Kissela, B. M., Knutson, K. L., … Martin, S. S. (2022). Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association. Circulation, 145(8), e153-e639. https://doi.org/10.1161/CIR.0000000000001052

The top 10 causes of death. (2020, December 9). Retrieved May 23, 2022, from https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death

Ferrannini, G., De Bacquer, D., De Backer, G., Kotseva, K., Mellbin, L., Wood, D., Rydén, L., & EUROASPIRE V collaborators (2020). Screening for Glucose Perturbations and Risk Factor Management in Dysglycemic Patients With Coronary Artery Disease-A Persistent Challenge in Need of Substantial Improvement: A Report From ESC EORP EUROASPIRE V. Diabetes care, 43(4), 726-733. https://doi.org/10.2337/dc19-2165

Mak, K. H., Vidal-Petiot, E., Young, R., Sorbets, E., Greenlaw, N., Ford, I., Tendera, M., Ferrari, R., Tardif, J. C., Udell, J. A., Escobedo, J., Fox, K. M., Steg, P. G., & CLARIFY Investigators (2022). Prevalence of diabetes and impact on cardiovascular events and mortality in patients with chronic coronary syndromes, across multiple geographical regions and ethnicities. European journal of preventive cardiology, 28(16), 1795-1806. https://doi.org/10.1093/eurjpc/zwab011

Cavender, M. A., Steg, P. G., Smith, S. C., Jr, Eagle, K., Ohman, E. M., Goto, S., Kuder, J., Im, K., Wilson, P. W., Bhatt, D. L., & REACH Registry Investigators (2015). Impact of Diabetes Mellitus on Hospitalization for Heart Failure, Cardiovascular Events, and Death: Outcomes at 4 Years from the Reduction of Atherothrombosis for Continued Health (REACH) Registry. Circulation, 132(10), 923-931. https://doi.org/10.1161/CIRCULATIONAHA.114.014796

Tang, N., Jiang, S., Yang, Y., Liu, S., Ponnusamy, M., Xin, H., & Yu, T. (2018). Noncoding RNAs as therapeutic targets in atherosclerosis with diabetes mellitus. Cardiovascular therapeutics, 36(4), e12436. https://doi.org/10.1111/1755-5922.12436

Zhao, S., Wang, H., Xu, H., Tan, Y., Zhang, C., Zeng, Q., Liu, L., & Qu, S. (2021). Targeting the microRNAs in exosome: A potential therapeutic strategy for alleviation of diabetes-related cardiovascular complication. Pharmacological research, 173, 105868. https://doi.org/10.1016/j.phrs.2021.105868

Mori, M. A., Ludwig, R. G., Garcia-Martin, R., Brandão, B. B., & Kahn, C. R. (2019). Extracellular miRNAs: From Biomarkers to Mediators of Physiology and Disease. Cell metabolism, 30(4), 656-673. https://doi.org/10.1016/j.cmet.2019.07.011

Chang, Y. J., & Wang, K. C. (2021). Therapeutic perspectives of extracellular vesicles and extracellular microRNAs in atherosclerosis. Current topics in membranes, 87, 255-277. https://doi.org/10.1016/bs.ctm.2021.08.005

Yu, B., Jiang, Y., Wang, X., & Wang, S. (2020). An integrated hypothesis for miR-126 in vascular disease. Medical research archives, 8(5), 2133. https://doi.org/10.18103/mra.v8i5.2133

Tang, S. T., Wang, F., Shao, M., Wang, Y., & Zhu, H. Q. (2017). MicroRNA-126 suppresses inflammation in endothelial cells under hyperglycemic condition by targeting HMGB1. Vascular pharmacology, 88, 48-55. https://doi.org/10.1016/j.vph.2016.12.002

Nigi, L., Grieco, G. E., Ventriglia, G., Brusco, N., Mancarella, F., Formichi, C., Dotta, F., & Sebastiani, G. (2018). MicroRNAs as Regulators of Insulin Signaling: Research Updates and Potential Therapeutic Perspectives in Type 2 Diabetes. International journal of molecular sciences, 19(12), 3705. https://doi.org/10.3390/ijms19123705

De Almeida-Faria, J., Duque-Guimarães, D. E., Ong, T. P., Pantaleão, L. C., Carpenter, A. A., Loche, E., Kusinski, L. C., Ashmore, T. J., Antrobus, R., Bushell, M., Fernandez-Twinn, D. S., & Ozanne, S. E. (2021). Maternal obesity during pregnancy leads to adipose tissue ER stress in mice via miR-126-mediated reduction in Lunapark. Diabetologia, 64(4), 890-902. https://doi.org/10.1007/s00125-020-05357-4

Sanguineti, R., Puddu, A., Nicolò, M., Traverso, C. E., Cordera, R., Viviani, G. L., & Maggi, D. (2021). miR-126 Mimic Counteracts the Increased Secretion of VEGF-A Induced by High Glucose in ARPE-19 Cells. Journal of diabetes research, 2021, 6649222. https://doi.org/10.1155/2021/6649222

Athira, S., Bhaskar, A., Misra, P., & Sibin, M. (2022). Circulatory miR-126 expression as an epigenetic marker in diabetes mellitus; a systematic review & meta-analysis. Gene Reports, 26, 101502. https://doi.org/10.1016/j.genrep.2022.101502

Kaur, A., Mackin, S. T., Schlosser, K., Wong, F. L., Elharram, M., Delles, C., Stewart, D. J., Dayan, N., Landry, T., & Pilote, L. (2020). Systematic review of microRNA biomarkers in acute coronary syndrome and stable coronary artery disease. Cardiovascular research, 116(6), 1113-1124. https://doi.org/10.1093/cvr/cvz302

Lin, D. C., Lin, J. B., Chen, Z., Chen, R., Wan, C. Y., Lin, S. W., Ruan, Q. S., Li, H. Y., & Wu, S. Y. (2017). Independent and combined effects of environmental factors and miR-126, miR-143, and miR-145 on the risk of coronary heart disease. Journal of geriatric cardiology : JGC, 14(11), 688-695. https://doi.org/10.11909/j.issn.1671-5411.2017.11.004

Trusinskis, K., Lapsovs, M., Paeglite, S., Knoka, E., Caunite, L., Mazule, M., Briede, I., Jegere, S., Kumsars, I., Narbute, I., Konrade, I., Erglis, A., & Lejnieks, A. (2021). Plasma circulating microRNAs in patients with stable coronary artery disease - Impact of different cardiovascular risk profiles and glomerular filtration rates. Journal of clinical and translational research, 7(2), 270-276. https://doi.org/10.18053/jctres.07.202102.014

Knoka, E., Trusinskis, K., Mazule, M., Briede, I., Crawford, W., Jegere, S., Kumsars, I., Narbute, I., Sondore, D., Lejnieks, A., & Erglis, A. (2020). Circulating plasma microRNA-126, microRNA-145, and microRNA-155 and their association with atherosclerotic plaque characteristics. Journal of clinical and translational research, 5(2), 60-67. https://doi.org/10.18053/jctres.05.201902.002

Fan, J. L., Zhang, L., & Bo, X. H. (2020). MiR-126 on mice with coronary artery disease by targeting S1PR2. European review for medical and pharmacological sciences, 24(2), 893-904. https://doi.org/10.26355/eurrev_202001_20074

Sheikh, M., Almaeen, A., Alduraywish, A., Alomair, B. M., Salma, U., Fei, L., & Yang, T. L. (2022). Overexpression of miR-126 Protects Hypoxic-Reoxygenation-Exposed HUVEC Cellular Injury through Regulating LRP6 Expression. Oxidative medicine and cellular longevity, 2022, 3647744. https://doi.org/10.1155/2022/3647744

Ali, W., Mishra, S., Rizvi, A., Pradhan, A., & Perrone, M. A. (2021). Circulating microRNA-126 as an Independent Risk Predictor of Coronary Artery Disease: A Case-Control Study. EJIFCC, 32(3), 347-362.

Mishra, S., Rizvi, A., Pradhan, A., Perrone, M. A., & Ali, W. (2021). Circulating microRNA-126 &122 in patients with coronary artery disease: Correlation with small dense LDL. Prostaglandins & other lipid mediators, 153, 106536. https://doi.org/10.1016/j.prostaglandins.2021.106536

Zhelankin, A. V., Stonogina, D. A., Vasiliev, S. V., Babalyan, K. A., Sharova, E. I., Doludin, Y. V., Shchekochikhin, D. Y., Generozov, E. V., & Akselrod, A. S. (2021). Circulating Extracellular miRNA Analysis in Patients with Stable CAD and Acute Coronary Syndromes. Biomolecules, 11(7), 962. https://doi.org/10.3390/biom11070962

Dai, R., Liu, Y., Zhou, Y., Xiong, X., Zhou, W., Li, W., Zhou, W., & Chen, M. (2020). Potential of circulating pro-angiogenic microRNA expressions as biomarkers for rapid angiographic stenotic progression and restenosis risks in coronary artery disease patients underwent percutaneous coronary intervention. Journal of clinical laboratory analysis, 34(1), e23013. https://doi.org/10.1002/jcla.23013

Vasu, S., Kumano, K., Darden, C. M., Rahman, I., Lawrence, M. C., & Naziruddin, B. (2019). MicroRNA Signatures as Future Biomarkers for Diagnosis of Diabetes States. Cells, 8(12), 1533. https://doi.org/10.3390/cells8121533

Mirra, P., Nigro, C., Prevenzano, I., Leone, A., Raciti, G. A., Formisano, P., Beguinot, F., & Miele, C. (2018). The Destiny of Glucose from a MicroRNA Perspective. Frontiers in endocrinology, 9, 46. https://doi.org/10.3389/fendo.2018.00046

Wang, X., Sundquist, J., Zöller, B., Memon, A. A., Palmér, K., Sundquist, K., & Bennet, L. (2014). Determination of 14 circulating microRNAs in Swedes and Iraqis with and without diabetes mellitus type 2. PloS one, 9(1), e86792. https://doi.org/10.1371/journal.pone.0086792

Zeinali, F., Aghaei Zarch, S. M., Jahan-Mihan, A., Kalantar, S. M., Vahidi Mehrjardi, M. Y., Fallahzadeh, H., Hosseinzadeh, M., Rahmanian, M., & Mozaffari-Khosravi, H. (2021). Circulating microRNA-122, microRNA-126-3p and microRNA-146a are associated with inflammation in patients with pre-diabetes and type 2 diabetes mellitus: A case control study. PloS one, 16(6), e0251697. https://doi.org/10.1371/journal.pone.0251697

Published

2022-10-22

How to Cite

1.
Serik SA, Mavrycheva NR, Bondar TM. Circulating microRNA-126 in patients with ischemic heart disease with type 2 diabetes mellitus and its relationship with glucometabolic disorders. Zaporozhye Medical Journal [Internet]. 2022Oct.22 [cited 2024Nov.25];24(5):501-8. Available from: http://zmj.zsmu.edu.ua/article/view/257413

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Section

Original research