The role of small noncoding RNAS in the pathogenesis of coronary arteries atherosclerosis
https://doi.org/10.18705/2311-4495-2018-5-3-5-14
Abstract
Background. Cardiovascular disease, including coronary artery disease (CAD), remains a leading cause of mortality. The results of recent studies demonstrate that microRNA engages in pathogenesis of different pathological states, including coronary atherosclerosis and its clinical manifestation — CAD.
Objective. To evaluate microRNA-27а, microRNA-133а and microRNA-203 expression in cardiomyocytes and blood serum of CAD patients with different degrees of coronary artery lesion.
Design and methods. 100 patients were included in the study, they formed 3 groups: 40 patients with CAD and significant atherosclerosis of 1-2 coronary arteries; 40 patients with multi arterial coronary disease and 20 persons without CAD and significant comorbidity. The microRNA-27a, microRNA-133а and microRNA-203 expression was determined in cardiomyocytes and blood serum of these patients by real-time polymerase chain reaction.
Results. Level of microRNA-27a, microRNA-133а and microRNA-203 expression in left atrium cardiomyocytes of CAD patients with significant stenosis of 3 or more coronary arteries was higher, then their expression in the patients with 1-2-vessel and in group without coronary atherosclerosis. Examination of the microRNA expression level in blood serum and in left atrium cardiomyocytes revealed a significant difference. The expression of microRNA-27a and microRNA-133а in cardiomyocytes is above than in blood serum, while the expression of microRNA-203 in the myocardium is lower, than in the blood serum. Level of microRNA-27a, microRNA-133а and microRNA-203 expression in blood serum in CAD patients with significant stenosis of 3 or more coronary arteries was significantly higher, than in patients with 1-2 stenosis of coronary arteries. Furthermore, classification tree method established that risk of atherosclerotic heart disease increases five-fold if microRNA-203 expression in blood serum is more than 100 REU.
Conclusion. MicroRNA-27а and microRNA-133а expression in cardiomyocytes of left atrium is higher than in blood serum in CAD patients. MicroRNA-203 expression level in blood serum may be a new predictive marker of coronary artery degree atherosclerotic stenosis in CAD patients.
About the Authors
E. A. PolyakovaRussian Federation
Ekaterina A. Polyakova - PhD, MD, researcher, department of arterial hypertension, academician I. P. Pavlov FSPSMU, researcher, laboratory of metabolic syndrome, Almazov NMRC.
L’va Tolstogo str. 6/8 Saint Petersburg, 197022
Competing Interests:
No conflict of interest
M. I. Zaraiskii
Russian Federation
Mikhail I. Zaraiskii - Dr. Sci., prof., Department of Clinical Laboratory Diagnostics.
L’va Tolstogo str. 6/8 Saint Petersburg, 197022
Competing Interests:
No conflict of interest
O. A. Berkovich
Russian Federation
Olga A. Berkovich - MD, prof., head of the laboratory of Cardiac ischemia, Academician I I. P. Pavlov FSPSMU.
L’va Tolstogo str. 6/8 Saint Petersburg, 197022
Competing Interests:
No conflict of interest
E. I. Baranova
Russian Federation
Elena I. Baranova - MD, Dr. Sci., the head of the laboratory of metabolic syndrome, Academician I. P. Pavlov FSPSMU.
L’va Tolstogo str. 6/8 Saint Petersburg, 197022
Competing Interests:
No conflict of interest
E. V. Shlyakhto
Russian Federation
Evgeniy V. Shlyakhto - acad., the head of Almazov NMRC.
L’va Tolstogo str. 6/8 Saint Petersburg, 197022
Competing Interests:
No conflict of interest
References
1. Ding X-Q, Ge P-C, Liu Z, et al. Interaction between microRNA expression and classical risk factors in the risk of coronary heart disease. Scientific Reports. 2015; 5:14925.
2. McPherson R, Tybjaerg-Hansen A. Genetics of Coronary Artery Disease. Circ Res. 2016; 118(4):564-578.
3. Chao C, Murugavel P, Cuiyun L, et al. MicroRNA as a Therapeutic Target in Cardiac Remodeling. BioMed Research International. 2017; 2017:1278436.
4. Kim YS, Ahn JS, Kim S, et al. The potential theragnostic (diagnostic+therapeutic) application of exosomes in diverse biomedical fields. Korean J Physiol Pharmacol. 2018; 22(2):113-125.
5. Sayed AS, Xia K, Yang TL, et al. Circulating microRNAs: a potential role in diagnosis and prognosis of acute myocardial infarction. Dis Markers. 2013; 35:561566.
6. Nishiguchi T, Imanishi T, Akasaka T. MicroRNAs and Cardiovascular Diseases. BioMed Research International. 2015; 2015:1-14.
7. Papageorgiou N, Tousoulis D, Charakida M, et al., Prognostic role of miRNAs in coronary artery disease. Curr. Top. Med. Chem. 2013; 13:1540-1547.
8. Hamed M, Gordon AF, Amir A, et al. Cytokines and MicroRNA in Coronary Artery Disease. Advances in Clinical Chemistry. 2017; 82:47-70.
9. Tian C, Gao L, Zimmerman MC, et al. Myocardial infarction-induced microRNA-enriched exosomes contribute to cardiac Nrf2 dysregulation in chronic heart failure. Am J Physiol Heart Circ Physiol. 2018; May 1; 314(5):H928-H939.
10. Bokeriya LA, Aronov DM. Russian clinical guidelines. Coronary artery bypass grafting in patients with ischemic heart disease: rehabilitation and secondary prevention. CardioSomatika. 2016; 7(3-4) :5-71. In Russian.
11. 2013 ESC Guidelines on the management of stable coronary artery disease. European Heart Journal. 2013; 34:2949-3003.
12. Zampetaki А, Katarzyna D, Mayr М. Oxidative stress in atherosclerosis: The role of microRNAs in arterial remodeling. Free Radical Biology and Medicine. 2013; 64:69–77.
13. Cipollone F, Felicioni L, Sarzani R, et al. A unique microRNA signature associated with plaque instability in humans. Stroke. 2011; 42:2556–2563.
14. Fedorov AV, Kostareva AA, Galagudza MM, et al. MicroRNA as biomarkers of myocardial ischemic injury: a perspective. Microcirculation. 2012; 11(3) :69-75. In Russian.
15. Syed SA, Chandra K, Mohd A, et al. Pathological microRNAs in acute cardiovascular diseases and microRNA therapeutics. Journal of Acute Disease. 2016; 5(1):9-15.
16. Jamaluddin MS, Weakley SM, Zhang L, et al. MiRNAs: roles and clinical applications in vascular disease. Expert Rev Mol Diagn. 2011; 11(1):79-89.
17. Alvarez ML, Khosroheidari M, Eddy E, et al. MicroRNA-27a decreases the level and efficiency of the LDL receptor and contributes to the dysregulation of cholesterol homeostasis. Atherosclerosis. 2015; 242(2):595604.
18. He Q, Wang C, Qin J, et al. Effect of miR-203 expression on myocardial fibrosis. European Review for Medical and Pharmacological Sciences. 2017; 21:837-842.
19. Zheng I, Jian X, Guo F, et al. miR-203 inhibits arecoline-induced epithelial-mesenchymal transition by regulating secreted frizzled-related protein 4 and transmembrane-4 L six family member 1 in oral submucous fibrosis. Oncol Rep. 2015; 33:2753-2760.
20. Wu-Jun C, Kai Y, Guo-Jun Z, et al. The magic and mystery of MicroRNA-27 in atherosclerosis. Atherosclerosis. 2012; 222:314– 323.
21. Navickas R, Gal D Laucevicˇius A, Taparauskaitė A, et al. Identifying circulating microRNAs as biomarkers of cardiovascular disease: a systematic review. Cardiovascular Research. 2016; 111:322–337.
22. Sattar N, Wannamethee G, Sarwar N, et al. Leptin and coronary heart disease: prospective study and systematic review. J Am Coll Cardiol. 2009; Jan 13; 53(2):167-175.
23. Abdellatif M. Differential Expression of MicroRNAs in Different Disease States. Circ Res. 2012; 110:638-650.
Review
For citations:
Polyakova E.A., Zaraiskii M.I., Berkovich O.A., Baranova E.I., Shlyakhto E.V. The role of small noncoding RNAS in the pathogenesis of coronary arteries atherosclerosis. Translational Medicine. 2018;5(3):5-14. (In Russ.) https://doi.org/10.18705/2311-4495-2018-5-3-5-14