Circulating miсroRNAs in patients with ischemic heart disease with type 2 diabetes mellitus

Authors

DOI:

https://doi.org/10.14739/2310-1237.2020.3.221727

Keywords:

coronary artery disease, type 2 diabetes mellitus, miсroRNA

Abstract

 

The aim of the study was to investigate circulating miRNAs-27a, -221 levels and their relationship with glycemia and insulin resistance in patients with ischemic heart disease (IHD) with type 2 diabetes mellitus.

Materials and methods. The study included 58 patients with stable IHD with type 2 diabetes and 22 patients with IHD without diabetes. The control group consisted of 19 healthy persons. MicroRNAs-27a and -221 were determined in blood plasma by real time polymerase chain reaction. Small nuclear RNA U6 was used as endogenous control.

Results. In patients with IHD with diabetes circulating microRNAs27a and -221 levels were lower than in the controls (P = 0.024, P = 0.006, respectively) and in nondiabetic patients with IHD (P = 0.011, P = 0.001, respectively). In nondiabetic patients with IHD microRNAs-27a and 221 levels were nonsignificantly higher than in the controls (P > 0.05, for both). In diabetic patients with IHD the positive correlation between microRNAs (R = 0.319, P = 0.027) was significantly weaker than in the controls (R = 0.889, P < 0.001) (P < 0.001) and in nondiabetic patients with IHD (R = 0.772, P < 0.001) (P = 0.020). In patients with IHD with diabetes microRNA-27a negatively correlated with glycosylated hemoglobin (R = -0.339, P = 0.030), and microRNA-221 negatively correlated with the HOMA-IR (R = -0.362, P = 0.006). According to the ROC-analysis the decrease of both miRNAs levels was significantly associated with the presence of diabetes in patients with IHD. AUC for microRNA-27a was 0.692 (CI: 0.575–0.793, P = 0.009), AUC for microRNA-221 was 0.728 (CI: 0.617–0.821, P = 0.001).

Conclusions. In patients with IHD with type 2 diabetes mellitus circulating microRNAs-27a and -221 levels significantly decreased in comparison with both control and patients with IHD without diabetes. The decrease of microRNA-27a was associated with hyperglycemia, and the decrease of microRNA-221 was associated with the increase of insulin resistance. In patients with IHD without diabetes these microRNAs levels did not change.

References

Einarson, T. R., Acs, A., Ludwig, C., & Panton, U. H. (2018). Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovascular diabetology, 17(1), 83. https://doi.org/10.1186/s12933-018-0728-6

Emerging Risk Factors Collaboration, Sarwar, N., Gao, P., Seshasai, S. R., Gobin, R., Kaptoge, S., Di Angelantonio, E., Ingelsson, E., Lawlor, D. A., Selvin, E., Stampfer, M., Stehouwer, C. D., Lewington, S., Pennells, L., Thompson, A., Sattar, N., White, I. R., Ray, K. K., & Danesh, J. (2010). Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Lancet, 375(9733), 2215-2222. https://doi.org/10.1016/S0140-6736(10)60484-9

Naito, R., & Miyauchi, K. (2017). Coronary Artery Disease and Type 2 Diabetes Mellitus. International Heart Journal, 58(4), 475-480. https://doi.org/10.1536/ihj.17-191

Santulli G. (2019). Editorial: Cardiovascular Disease and Diabetes. Frontiers in endocrinology, 10, 314. https://doi.org/10.3389/fendo.2019.00314

De Rosa, S., Arcidiacono, B., Chiefari, E., Brunetti, A., Indolfi, C., & Foti, D. P. (2018). Type 2 Diabetes Mellitus and Cardiovascular Disease: Genetic and Epigenetic Links. Frontiers in endocrinology, 9, 2. https://doi.org/10.3389/fendo.2018.00002

Das, A., Samidurai, A., & Salloum, F. N. (2018). Deciphering Non-coding RNAs in Cardiovascular Health and Disease. Frontiers in cardiovascular medicine, 5, 73. https://doi.org/10.3389/fcvm.2018.00073

Çakmak, H. A., & Demir, M. (2020). MicroRNA and Cardiovascular Diseases. Balkan medical journal, 37(2), 60-71. https://doi.org/10.4274/balkanmedj.galenos.2020.2020.1.94

Friedman, R. C., Farh, K. K., Burge, C. B., & Bartel, D. P. (2009). Most mammalian mRNAs are conserved targets of microRNAs. Genome research, 19(1), 92-105. https://doi.org/10.1101/gr.082701.108

Kozomara, A., Birgaoanu, M., & Griffiths-Jones, S. (2019). miRBase: from microRNA sequences to function. Nucleic acids research, 47(D1), D155-D162. https://doi.org/10.1093/nar/gky1141

O'Brien, J., Hayder, H., Zayed, Y., & Peng, C. (2018). Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Frontiers in endocrinology, 9, 402. https://doi.org/10.3389/fendo.2018.00402

Chen, W. J., Yin, K., Zhao, G. J., Fu, Y. C., & Tang, C. K. (2012). The magic and mystery of microRNA-27 in atherosclerosis. Atherosclerosis, 222(2), 314-323. https://doi.org/10.1016/j.atherosclerosis.2012.01.020

Chistiakov, D. A., Sobenin, I. A., Orekhov, A. N., & Bobryshev, Y. V. (2015). Human miR-221/222 in Physiological and Atherosclerotic Vascular Remodeling. BioMed research international, 2015, 1-18. https://doi.org/10.1155/2015/354517

Chen, T., Zhang, Y., Liu, Y., Zhu, D., Yu, J., Li, G., Sun, Z., Wang, W., Jiang, H., & Hong, Z. (2019). MiR-27a promotes insulin resistance and mediates glucose metabolism by targeting PPAR-γ-mediated PI3K/AKT signaling. Aging, 11(18), 7510-7524. https://doi.org/10.18632/aging.102263

Huang, F., Chen, J., Wang, J., Zhu, P., & Lin, W. (2019). Palmitic Acid Induces MicroRNA-221 Expression to Decrease Glucose Uptake in HepG2 Cells via the PI3K/AKT/GLUT4 Pathway. BioMed research international, 2019, 8171989. https://doi.org/10.1155/2019/8171989

Fichtlscherer, S., De Rosa, S., Fox, H., Schwietz, T., Fischer, A., Liebetrau, C., Weber, M., Hamm, C. W., Röxe, T., Müller-Ardogan, M., Bonauer, A., Zeiher, A. M., & Dimmeler, S. (2010). Circulating microRNAs in patients with coronary artery disease. Circulation research, 107(5), 677-684. https://doi.org/10.1161/CIRCRESAHA.109.215566

Draganova, A. S., Polyakova, E. A., Kolodina, D. A., Mikheeva, K. Yu., Belyaeva, O. D., Zaraysky, M. I., Berkovich, O. A., & Shlyakhto, E. V. (2019). Expression of miRNA-27a in the serum of patients with non-ST elevation acute coronary syndrome who underwent percutaneous coronary intervention. Russian Journal of Cardiology, (2), 70-75. https://doi.org/10.15829/1560-4071-2019-2-70-75

Karolina, D. S., Tavintharan, S., Armugam, A., Sepramaniam, S., Pek, S. L., Wong, M. T., Lim, S. C., Sum, C. F., & Jeyaseelan, K. (2012). Circulating miRNA profiles in patients with metabolic syndrome. The Journal of clinical endocrinology and metabolism, 97(12), E2271-E2276. https://doi.org/10.1210/jc.2012-1996

de Candia, P., Spinetti, G., Specchia, C., Sangalli, E., La Sala, L., Uccellatore, A., Lupini, S., Genovese, S., Matarese, G., & Ceriello, A. (2017). A unique plasma microRNA profile defines type 2 diabetes progression. PloS one, 12(12), e0188980. https://doi.org/10.1371/journal.pone.0188980

Shvangiradze, T., Bondarenko, I., Troshina, E., Shestakova, M., Ilyin, A., Nikankina, L., Karpukhin, A., Muzaffarova, T., Kipkeeva, F., Grishina, K., & Kuzevanova, A. (2016). Profil mikroRNK, assotsiirovannykh s IBS, u patsientov s sakharnym diabetom 2 tipa [Profile of microRNAs associated with coronary heart disease in patients with type 2 diabetes]. Obesity and Metabolism, 13(4), 34-38. [in Russian].

Yilmaz, S., Isbir, S., Kunt, A., & Isbir, T. Circulating microRNAs as Novel Biomarkers for Atherosclerosis. (2018). In Vivo, 32(3), 561-565. https://doi.org/10.21873/invivo.11276

Liu, H. N., Li, X., Wu, N., Tong, M. M., Chen, S., Zhu, S. S., Qian, W., & Chen, X. L. (2018). Serum microRNA-221 as a biomarker for diabetic retinopathy in patients associated with type 2 diabetes. International journal of ophthalmology, 11(12), 1889-1894. https://doi.org/10.18240/ijo.2018.12.02

Xie, W., Li, L., Zhang, M., Cheng, H., Gong, D., Lv, Y., … Tang, C. K. (2016). MicroRNA-27 Prevents Atherosclerosis by Suppressing Lipoprotein Lipase-Induced Lipid Accumulation and Inflammatory Response in Apolipoprotein E Knockout Mice. PloS one, 11(6), e0157085. https://doi.org/10.1371/journal.pone.0157085

Yu Y., Du H., Wei S., Feng L., Li J., Yao F., Zhang M., Hatch G. M., & Chen L. (2018). Adipocyte-Derived Exosomal MiR-27a Induces Insulin Resistance in Skeletal Muscle Through Repression of PPARγ. Theranostics, 8(8), 2171-2188. https://doi.org/10.7150/thno.22565

Wang, S., Ai, H., Liu, L., Zhang, X., Gao, F., Zheng, L., Yi, J., Sun, L., Yu, C., Zhao, H., & Li, Y. (2019). Micro-RNA-27a/b negatively regulates hepatic gluconeogenesis by targeting FOXO1. American journal of physiology. Endocrinology and metabolism, 317(5), E911-E924. https://doi.org/10.1152/ajpendo.00190.2019

Ye, J., Wu, Y., Guo, R., Zeng, W., Duan, Y., Yang, Z., & Yang, L. (2019). miR-221 Alleviates the Ox-LDL-Induced Macrophage Inflammatory Response via the Inhibition of DNMT3b-Mediated NCoR Promoter Methylation. Mediators of inflammation, 2019, 4530534. https://doi.org/10.1155/2019/4530534

Chen, C. F., Huang, J., Li, H., Zhang, C., Huang, X., Tong, G., & Xu, Y. Z. (2015). MicroRNA-221 regulates endothelial nitric oxide production and inflammatory response by targeting adiponectin receptor 1. Gene, 565(2), 246-251. https://doi.org/10.1016/j.gene.2015.04.014

Deiuliis J. A. (2016). MicroRNAs as regulators of metabolic disease: pathophysiologic significance and emerging role as biomarkers and therapeutics. International journal of obesity, 40(1), 88-101. https://doi.org/10.1038/ijo.2015.170

Peng, J., Zhou, Y., Deng, Z., Zhang, H., Wu, Y., Song, T., Yang, Y., Wei, H., & Peng, J. (2018). miR-221 negatively regulates inflammation and insulin sensitivity in white adipose tissue by repression of sirtuin-1 (SIRT1). Journal of cellular biochemistry, 119(8), 6418-6428. https://doi.org/10.1002/jcb.26589

Vegter, E. L., Ovchinnikova, E. S., van Veldhuisen, D. J., Jaarsma, T., Berezikov, E., van der Meer, P., & Voors, A. A. (2017). Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations. Clinical research in cardiology : official journal of the German Cardiac Society, 106(8), 598-609. https://doi.org/10.1007/s00392-017-1096-z

Togliatto, G., Trombetta, A., Dentelli, P., Rosso, A., & Brizzi, M. F. (2011). MIR221/MIR222-driven post-transcriptional regulation of P27KIP1 and P57KIP2 is crucial for high-glucose- and AGE-mediated vascular cell damage. Diabetologia, 54(7), 1930. https://doi.org/10.1007/s00125-011-2125-5

Granjon, A., Gustin, M. P., Rieusset, J., Lefai, E., Meugnier, E., Güller, I., Cerutti, C., Paultre, C., Disse, E., Rabasa-Lhoret, R., Laville, M., Vidal, H., & Rome, S. (2009). The microRNA signature in response to insulin reveals its implication in the transcriptional action of insulin in human skeletal muscle and the role of a sterol regulatory element-binding protein-1c/myocyte enhancer factor 2C pathway. Diabetes, 58(11), 2555-2564. https://doi.org/10.2337/db09-0165

Bildirici, A. E., Arslan, S., Özbilüm Şahin, N., Berkan, Ö., Beton, O., & Yilmaz, M. B. (2018). MicroRNA-221/222 expression in atherosclerotic coronary artery plaque versus internal mammarian artery and in peripheral blood samples. Biomarkers, 23(7), 670-675. https://doi.org/10.1080/1354750X.2018.1474260

Karolina, D. S., Armugam, A., Tavintharan, S., Wong, M. T., Lim, S. C., Sum, C. F., & Jeyaseelan, K. (2011). MicroRNA 144 impairs insulin signaling by inhibiting the expression of insulin receptor substrate 1 in type 2 diabetes mellitus. PloS one, 6(8), e22839. https://doi.org/10.1371/journal.pone.0022839

Nunez Lopez, Y. O., Garufi, G., & Seyhan, A. A. (2016). Altered levels of circulating cytokines and microRNAs in lean and obese individuals with prediabetes and type 2 diabetes. Molecular bioSystems, 13(1), 106-121. https://doi.org/10.1039/c6mb00596a

Jia, Q. W., Chen, Z. H., Ding, X. Q., Liu, J. Y., Ge, P. C., An, F. H., Li, L. H., Wang, L. S., Ma, W. Z., Yang, Z. J., & Jia, E. Z. (2017). Predictive Effects of Circulating miR-221, miR-130a and miR-155 for Coronary Heart Disease: A Multi-Ethnic Study in China. Cellular physiology and biochemistry, 42(2), 808-823. https://doi.org/10.1159/000478071

Ding, X. Q., Ge, P. C., Liu, Z., Jia, H., Chen, X., An, F. H., … Jia, E. Z. (2015). Interaction between microRNA expression and classical risk factors in the risk of coronary heart disease. Scientific reports, 5, 14925. https://doi.org/10.1038/srep14925

Li, M. Y., Pan, S. R., & Qiu, A. Y. (2016). Roles of microRNA-221/222 in type 2 diabetic patients with post-menopausal breast cancer. Genetics and molecular research: GMR, 15(2), 10.4238/gmr.15027259. https://doi.org/10.4238/gmr.15027259

Mononen, N., Lyytikäinen, L., Seppälä, I., Mishra, P., Juonala, M., Waldenberger, M. … Raitoharju, E. (2019). Whole blood microRNA levels associate with glycemic status and correlate with target mRNAs in pathways important to type 2 diabetes. Scientific Reports, 9(1), 8887. https://doi.org/10.1038/s41598-019-43793-4

Stępień, E., Durak-Kozica, M., Kamińska, A., Targosz-Korecka, M., Libera, M., Tylko, G. … Enguita, F. J. (2018). Circulating ectosomes: Determination of angiogenic microRNAs in type 2 diabetes. Theranostics, 8(14), 3874-3890. https://doi.org/10.7150/thno.23334

Viereck, J., & Thum, T. (2017). Circulating Noncoding RNAs as Biomarkers of Cardiovascular Disease and Injury. Circulation research, 120(2), 381-399. https://doi.org/10.1161/CIRCRESAHA.116.308434

How to Cite

1.
Serik SA, Serdobinska-Kanivets EM, Bondar TM. Circulating miсroRNAs in patients with ischemic heart disease with type 2 diabetes mellitus. Pathologia [Internet]. 2020Dec.29 [cited 2024Apr.26];(3). Available from: http://pat.zsmu.edu.ua/article/view/221727

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Original research