MicroRNAs and Oxidative Stress Markers as Additional Diagnostic Criteria for Coronary Heart Disease

  • Oksana Yu. Marchenko Department of Children’s Cardiology and Cardiac Surgery, Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine; Cardiovascular Division, King’s College London, London, United Kingdom https://orcid.org/0000-0003-4909-8347
  • Nadiya M. Rudenko Department of Children’s Cardiology and Cardiac Surgery, Shupyk National Healthcare University of Ukraine, Kyiv, Ukraine; Ukrainian Children’s Cardiac Center, Kyiv, Ukraine https://orcid.org/0000-0002-1681-598X
  • Dmytro S. Krasnienkov D. F. Chebotarev Institute of Gerontology of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine https://orcid.org/0000-0002-0774-637X
Keywords: miRNA-122, glutathione, lipoprotein, biomarker, atherosclerosis, ischemic heart disease

Abstract

The aim. To examine the significance of microribonucleic acids (miRNAs) and oxidative stress markers in predicting the onset of atherosclerosis and the connection between oxidative stress levels and miRNAs in individuals with coronary heart disease.

Materials and methods. Initially, 40 patients were divided as follows: 10 subjects without any lesions in coronary arteries (group 0), 4 patients with non-stenotic atherosclerosis (group 1), and 26 patients with significant multivessel atherosclerotic lesions (group 2). Various biochemical parameters were analyzed, including miRNA expression levels and common oxidative stress markers.

Results. The groups were comparable in terms of the patients’ age, but there was unequal distribution of males and females in the angio-groups as per Fisher’s exact test. We also analyzed the data separately for females, but no significant difference was found. There were significant differences in miRNA-122 levels, N-terminal prohormone of brain natriuretic peptide levels, lipid profiles, and oxidative stress markers between group 0 and groups with atherosclerotic lesions. Specifically, miRNA-122 levels were elevated in group 0, along with N-terminal prohormone of brain natriuretic peptide, triglycerides, ratio of triglycerides to high-density lipoprotein cholesterol, and oxidative stress markers. Conversely, compared to group 0, total cholesterol, high-density lipoprotein cholesterol, bilirubin, and specific glutathione levels decreased in patients with coronary lesions.

Conclusions. The study demonstrated the potential of miRNAs, particularly miRNA-122, as predictive biomarkers for atherosclerosis. Further research with larger cohorts is warranted to validate these findings and explore additional miRNA candidates and therapeutic interventions for cardiovascular diseases.

References

  1. Liu Y, Song JW, Lin JY, Miao R, Zhong JC. Roles of MicroRNA-122 in Cardiovascular Fibrosis and Related Diseases. Cardiovasc Toxicol. 2020;20(5):463-473. https://doi.org/10.1007/s12012-020-09603-4
  2. Li Y, Jin P, Hou F, Zhou Y. Association Between TG-to-HDL-C Ratio and In-Stent Stenosis Under Optical Coherence Tomography Guidance. J Med Syst. 2018 Nov 20;43(1):4. https://doi.org/10.1007/s10916-018-1119-y
  3. Vítek L, Jirásková A, Malíková I, Dostálová G, Eremiášová L, Danzig V, et al. Serum Bilirubin and Markers of Oxidative Stress and Inflammation in a Healthy Population and in Patients with Various Forms of Atherosclerosis. Antioxidants (Basel). 2022 Oct 27;11(11):2118. https://doi.org/10.3390/antiox11112118
  4. You L, Chen H, Xu L, Li X. Overexpression of miR-29a-3p Suppresses Proliferation, Migration, and Invasion of Vascular Smooth Muscle Cells in Atherosclerosis via Targeting TNFRSF1A. Biomed Res Int. 2020 Sep 4;2020:9627974. https://doi.org/10.1155/2020/9627974
  5. Assmann TS, Milagro FI, Martínez JA. Crosstalk between microRNAs, the putative target genes and the lncRNA network in metabolic diseases. Mol Med Rep. 2019;20(4):3543-3554. https://doi.org/10.3892/mmr.2019.10595
  6. D’Oria R, Schipani R, Leonardini A, Natalicchio A, Perrini S, Cignarelli A, et al. The Role of Oxidative Stress in Cardiac Disease: From Physiological Response to Injury Factor. Oxid Med Cell Longev. 2020 May 14;2020:5732956. https://doi.org/10.1155/2020/5732956
  7. Panda P, Verma HK, Lakkakula S, Merchant N, Kadir F, Rahman S, et al. Biomarkers of Oxidative Stress Tethered to Cardiovascular Diseases. Oxid Med Cell Longev. 2022 Jun 24;2022:9154295. https://doi.org/10.1155/2022/9154295
  8. McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods. 23rd ed. St. Louis (MO):Elsevier;2016.
  9. Guescini M, Sisti D, Rocchi MB, Stocchi L, Stocchi V. A new real-time PCR method to overcome significant quantitative inaccuracy due to slight amplification inhibition. BMC Bioinformatics. 2008 Jul 30;9:326. https://doi.org/10.1186/1471-2105-9-326
  10. Stoscheck CM. Quantitation of protein. Methods Enzymol. 1990;182:50-68. https://doi.org/10.1016/0076-6879(90)82008-p
  11. Pia de la Maza M, Garrido F, Escalante N, Leiva L, Barrera G, Schnitzler S, et al. Fluorescent advanced glycation end-products (ages) detected by spectro-photofluorimetry, as a screening tool to detect diabetic microvascular complications. J Diabetes Mellitus. 2012;2(2):221-226. https://doi.org/10.4236/jdm.2012.22035
  12. Hamad A, Elshahawy M, Negm A, Mansour F. Analytical methods for determination of glutathione and glutathione disulfide in pharmaceuticals and biological fluids. Rev Anal Chem. 2019;38(4):20190019. https://doi.org/10.1515/revac-2019-0019
  13. Mahjoob G, Ahmadi Y, Fatima Rajani H, Khanbabaei N, Abolhasani S. Circulating microRNAs as predictive biomarkers of coronary artery diseases in type 2 diabetes patients. J Clin Lab Anal. 2022 May;36(5):e24380. https://doi.org/10.1002/jcla.24380
  14. Malekmohammad K, Bezsonov EE, Rafieian-Kopaei M. Role of Lipid Accumulation and Inflammation in Atherosclerosis: Focus on Molecular and Cellular Mechanisms. Front Cardiovasc Med. 2021 Sep 6;8:707529. https://doi.org/10.3389/fcvm.2021.707529
  15. Song JJ, Yang M, Liu Y, Song JW, Wang J, Chi HJ, et al. MicroRNA-122 aggravates angiotensin II-mediated apoptosis and autophagy imbalance in rat aortic adventitial fibroblasts via the modulation of SIRT6-elabela-ACE2 signaling. Eur J Pharmacol. 2020 Sep 15;883:173374. https://doi.org/10.1016/j.ejphar.2020.173374
  16. Li HQ, Pan ZY, Yang Z, Zhang DB, Chen Q. Overexpression of MicroRNA-122 Resists Oxidative Stress-Induced Human Umbilical Vascular Endothelial Cell Injury by Inhibition of p53. Biomed Res Int. 2020 Oct 27;2020:9791608. https://doi.org/10.1155/2020/9791608
  17. Pagan LU, Gomes MJ, Gatto M, Mota GAF, Okoshi K, Okoshi MP. The Role of Oxidative Stress in the Aging Heart. Antioxidants (Basel). 2022 Feb 9;11(2):336. https://doi.org/10.3390/antiox11020336
  18. Zhang X, McLendon JM, Peck BD, Chen B, Song LS, Boudreau RL. Modulation of miR-29 influences myocardial compliance likely through coordinated regulation of calcium handling and extracellular matrix. Mol Ther Nucleic Acids. 2023 Nov 17;34:102081. https://doi.org/10.1016/j.omtn.2023.102081
  19. Liu ZY, Song K, Tu B, Lin LC, Sun H, Zhou Y, et al. Crosstalk between oxidative stress and epigenetic marks: New roles and therapeutic implications in cardiac fibrosis. Redox Biol. 2023 Sep;65:102820. https://doi.org/10.1016/j.redox.2023.102820
  20. Desantis V, Potenza MA, Sgarra L, Nacci C, Scaringella A, Cicco S, et al. microRNAs as Biomarkers of Endothelial Dysfunction and Therapeutic Target in the Pathogenesis of Atrial Fibrillation. Int J Mol Sci. 2023 Mar 10;24(6):5307. https://doi.org/10.3390/ijms24065307
  21. Generoso G, Janovsky CCPS, Bittencourt MS. Triglycerides and triglyceride-rich lipoproteins in the development and progression of atherosclerosis. Curr Opin Endocrinol Diabetes Obes. 2019;26(2):109-116. https://doi.org/10.1097/MED.0000000000000468
  22. Macvanin M, Obradovic M, Zafirovic S, Stanimirovic J, Isenovic ER. The Role of miRNAs in Metabolic Diseases. Curr Med Chem. 2023;30(17):1922-1944. https://doi.org/10.2174/0929867329666220801161536
  23. Kramna D, Riedlova P, Jirik V. MicroRNAs as a Potential Biomarker in the Diagnosis of Cardiovascular Diseases. Medicina (Kaunas). 2023 Jul 19;59(7):1329. https://doi.org/10.3390/medicina59071329
  24. Achmad H, Almajidi YQ, Adel H, Obaid RF, Romero-Parra RM, Kadhum WR, et al. The emerging crosstalk between atherosclerosis-related microRNAs and Bermuda triangle of foam cells: Cholesterol influx, trafficking, and efflux. Cell Signal. 2023 Jun;106:110632. https://doi.org/10.1016/j.cellsig.2023.110632
  25. Graham A. Modulation of the Cellular microRNA Landscape: Contribution to the Protective Effects of High-Density Lipoproteins (HDL). Biology (Basel). 2023 Sep 13;12(9):1232. https://doi.org/10.3390/biology12091232
  26. Zhang L, Cheng H, Yue Y, Li S, Zhang D, He R. TUG1 knockdown ameliorates atherosclerosis via up-regulating the expression of miR-133a target gene FGF1. Cardiovasc Pathol. 2018;33:6-15. https://doi.org/10.1016/j.carpath.2017.11.004
  27. Li RT, Li Y, Wang BW, Gao XQ, Zhang JX, Li F, et al. Relationship between plasma glutamate and cardiovascular disease risk in Chinese patients with type 2 diabetes mellitus by gender. Front Endocrinol (Lausanne). 2023 Apr 12;14:1095550. https://doi.org/10.3389/fendo.2023.1095550
  28. Ferreira-Cravo M, Moreira DC, Hermes-Lima M. Glutathione Depletion Disrupts Redox Homeostasis in an Anoxia-Tolerant Invertebrate. Antioxidants (Basel). 2023 May 31;12(6):1197. https://doi.org/10.3390/antiox12061197
  29. Zhang X, Min X, Li C, Benjamin IJ, Qian B, Zhang X, et al. Involvement of Reductive Stress in the Cardiomyopathy in Transgenic Mice With Cardiac-Specific Overexpression of Heat Shock Protein 27. Hypertension. 2010;55(6):1412-1417. https://doi.org/10.1161/HYPERTENSIONAHA.109.147066
  30. Rajasekaran NS, Connell P, Christians ES, Yan LJ, Taylor RP, Orosz A, et al. Human αB-Crystallin Mutation Causes Oxido-Reductive Stress and Protein Aggregation Cardiomyopathy in Mice. Cell. 2007;130(3):427-439. https://doi.org/10.1016/j.cell.2007.06.044
  31. Kundur AR, Singh I, Bulmer AC. Bilirubin, platelet activation and heart disease: A missing link to cardiovascular protection in Gilbert’s syndrome? Atherosclerosis. 2015;239(1):73-84. https://doi.org/10.1016/j.atherosclerosis.2014.12.042
  32. Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S. The current state of serum biomarkers of hepatotoxicity. Toxicology. 2008;245(3):194-205. https://doi.org/10.1016/j.tox.2007.11.021
  33. Kan Changez MI, Mubeen M, Zehra M, Samnani I, Abdul Rasool A, Mohan A, et al. Role of microRNA in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH): a comprehensive review. J Int Med Res. 2023 Sep;51(9):3000605231197058. https://doi.org/10.1177/03000605231197058
Published
2024-03-27
How to Cite
Marchenko, O. Y., Rudenko, N. M., & Krasnienkov, D. S. (2024). MicroRNAs and Oxidative Stress Markers as Additional Diagnostic Criteria for Coronary Heart Disease. Ukrainian Journal of Cardiovascular Surgery, 32(1), 10-19. https://doi.org/10.30702/ujcvs/24.32(01)/MR013-1019