Document Type : Original Article(s)


1 Department of Medical Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

2 Department of Cardiology, School of Medicine AND Research Center for Prevention of Cardiovascular Endocrinology and Metabolism, Research Institute Hazrat-e Rasool General Hospital, Iran University of Medical Sciences, Tehran, Iran

3 Department of Virology, School of Medicine AND Research Center of Pediatric Infectious Diseases, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran

4 Infectious Disease Research Center, Birjand University of Medical Sciences, Birjand, Iran

5 Department of Bacteriology and Virology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

6 Department of Medical Laboratory Sciences, School of Paramedicine, Alborz University of Medical Sciences, Karaj, Iran

7 Iranian Blood Transfusion Organization, Tehran, Iran


BACKGROUND: Coronary artery disease (CAD) is a leading cause of death around the world. Micro-ribonucleic acid (miRNA) can be involved in forming of atherosclerotic plaques, inflammation, cholesterol metabolism, and other mechanisms involved in CAD development. This study aimed to evaluate the expression level of miR-22, miR-30c, miR-145, and miR-519d and their possible association with inflammatory markers among patients with CAD.
METHODS: The expression level of miR-22, miR-30c, miR-145, miR-519d, interleukin 6 (IL-6), and transforming growth factor beta (TGF-β) was determined in peripheral blood mononuclear cells (PBMCs) from 46 patients with CAD and 39 healthy controls using real-time quantitative polymerase chain reaction (qPCR) assay.
RESULTS: 53.8% (n = 21) and 52.2% (n = 24) of controls and cases were men, respectively; the mean age was 59.8 ± 7.4 and 57.0 ± 9.8 years, respectively. The miRNA expression pattern of each group showed significantly different expression profiles. In the CAD patients group, miR-22, miR-30c, and miR-145 were down-regulated compared to the control group. On the opposite, miR-519d was up-regulated in patients with CAD compared to the control group. Our results also showed that the expression levels of IL-6 and TGF-β were up-regulated among patients with CAD compared to the control group. In addition, the expression of miR-145 and miR-519d had a significantly negative and positive correlation with TGF-β and IL-6, respectively.
CONCLUSION: The change in expression levels of miR-22, miR-30c, miR-145, and miR-519d in PBMCs of patients with CAD could be considered as a potential biomarker for CAD.


  1. Fazmin IT, Achercouk Z, Edling CE, Said A, Jeevaratnam K. Circulating microRNA as a biomarker for coronary artery disease. Biomolecules 2020; 10(10): 1354.
  2. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016; 388(10053): 1545-602.
  3. GBD 2015 Mortality and Causes of Death Collaborators. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016; 388(10053): 1459-544.
  4. Chen LJ, Lim SH, Yeh YT, Lien SC, Chiu JJ. Roles of microRNAs in atherosclerosis and restenosis. J Biomed Sci 2012; 19(1): 79.
  5. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 2005; 352(16): 1685-95.
  6. Gimbrone MA, Garcia-Cardena G. Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res 2016; 118(4): 620-36.
  7. Thakore AH, Guo CY, Larson MG, Corey D, Wang TJ, Vasan RS, et al. Association of multiple inflammatory markers with carotid intimal medial thickness and stenosis (from the Framingham Heart Study). Am J Cardiol 2007; 99(11): 1598-602.
  8. Campos H, Genest JJ, Blijlevens E, McNamara JR, Jenner JL, Ordovas JM, et al. Low density lipoprotein particle size and coronary artery disease. Arterioscler Thromb 1992; 12(2): 187-95.
  9. Saadati S, Eskandari V, Rahmani F, Mahmoudi MJ, Rahnemoon Z, Rahmati Z, et al. Gene expression and levels of TGF-B in PBMC is associated with severity of symptoms in chronic heart failure. Avicenna J Med Biotechnol 2020; 12(2): 132-4.
  10. Bai Y, Zhang P, Zhang X, Huang J, Hu S, Wei Y. LTBP-2 acts as a novel marker in human heart failure - a preliminary study. Biomarkers 2012; 17(5): 407-15.
  11. Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J, et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 2010; 31(6): 659-66.
  12. Keshavarz M, Dianat-Moghadam H, Sofiani VH, Karimzadeh M, Zargar M, Moghoofei M, et al. miRNA-based strategy for modulation of influenza A virus infection. Epigenomics 2018; 10(6): 829-44.
  13. Satoh M, Takahashi Y, Tabuchi T, Tamada M, Takahashi K, Itoh T, et al. Circulating Toll-like receptor 4-responsive microRNA panel in patients with coronary artery disease: Results from prospective and randomized study of treatment with renin-angiotensin system blockade. Clin Sci (Lond ) 2015; 128(8): 483-91.
  14. Kadam P, Bhalerao S. Sample size calculation. Int J Ayurveda Res 2010; 1(1): 55-7.
  15. Chen KC, Juo SH. MicroRNAs in atherosclerosis. Kaohsiung J Med Sci 2012; 28(12): 631-40.
  16. Flowers E, Froelicher ES, Aouizerat BE. MicroRNA regulation of lipid metabolism. Metabolism 2013; 62(1): 12-20.
  17. Guo X, Li D, Chen M, Chen L, Zhang B, Wu T, et al. miRNA-145 inhibits VSMC proliferation by targeting CD40. Sci Rep 2016; 6: 35302.
  18. Wang D, Atanasov AG. The microRNAs regulating vascular smooth muscle cell proliferation: A minireview. Int J Mol Sci 2019; 20(2).
  19. Essandoh K, Li Y, Huo J, Fan GC. MiRNA-mediated macrophage polarization and its potential role in the regulation of inflammatory response. Shock 2016; 46(2): 122-31.
  20. Moore KJ, Rayner KJ, Suarez Y, Fernandez-Hernando C. The role of microRNAs in cholesterol efflux and hepatic lipid metabolism. Annu Rev Nutr 2011; 31: 49-63.
  21. Bidzhekov K, Gan L, Denecke B, Rostalsky A, Hristov M, Koeppel TA, et al. microRNA expression signatures and parallels between monocyte subsets and atherosclerotic plaque in humans. Thromb Haemost 2012; 107(4): 619-25.
  22. Zhang Y, Zhang L, Wang Y, Ding H, Xue S, Qi H, et al. MicroRNAs or long noncoding RNAs in diagnosis and prognosis of coronary artery disease. Aging Dis 2019; 10(2): 353-66.
  23. Melak T, Baynes HW. Circulating microRNAs as possible biomarkers for coronary artery disease: a narrative review. EJIFCC 2019; 30(2): 179-94.
  24. Roifman I, Beck PL, Anderson TJ, Eisenberg MJ, Genest J. Chronic inflammatory diseases and cardiovascular risk: A systematic review. Can J Cardiol 2011; 27(2): 174-82.
  25. Ling B, Wang GX, Long G, Qiu JH, Hu ZL. Tumor suppressor miR-22 suppresses lung cancer cell progression through post-transcriptional regulation of ErbB3. J Cancer Res Clin Oncol 2012; 138(8): 1355-61.
  26. Yang QY, Yang KP, Li ZZ. MiR-22 restrains proliferation of rheumatoid arthritis by targeting IL6R and may be concerned with the suppression of NF-kappaB pathway. Kaohsiung J Med Sci 2020; 36(1): 20-6.
  27. Huang WQ, Wei P, Lin RQ, Huang F. Protective effects of microrna-22 against endothelial cell injury by targeting NLRP3 through suppression of the inflammasome signaling pathway in a rat model of coronary heart disease. Cell Physiol Biochem 2017; 43(4): 1346-58.
  28. Anderson DR, Poterucha JT, Mikuls TR, Duryee MJ, Garvin RP, Klassen LW, et al. IL-6 and its receptors in coronary artery disease and acute myocardial infarction. Cytokine 2013; 62(3): 395-400.
  29. Chen B, Luo L, Zhu W, Wei X, Li S, Huang Y, et al. miR-22 contributes to the pathogenesis of patients with coronary artery disease by targeting MCP-1: An observational study. Medicine (Baltimore) 2016; 95(33): e4418.
  30. Soh J, Iqbal J, Queiroz J, Fernandez-Hernando C, Hussain MM. MicroRNA-30c reduces hyperlipidemia and atherosclerosis in mice by decreasing lipid synthesis and lipoprotein secretion. Nat Med 2013; 19(7): 892-900.
  31. Gatling AM. The Role of MicroRNA-30C in Regulating Plasma Lipids in MicroRNA-30C Double Knockout Mice [MSc Thesis]. Albany, NY: State University of New York; 2018.
  32. AIM-HIGH Investigators. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol Rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH). Am Heart J 2011; 161(3): 471-7.
  33. Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017; 38(32): 2459-72.
  34. Ceolotto G, Giannella A, Albiero M, Kuppusamy M, Radu C, Simioni P, et al. miR-30c-5p regulates macrophage-mediated inflammation and pro-atherosclerosis pathways. Cardiovasc Res 2017; 113(13): 1627-38.
  35. Zhao W, Zhao SP, Zhao YH. MicroRNA-143/-145 in cardiovascular diseases. Biomed Res Int 2015; 2015: 531740.
  36. Zhao N, Koenig SN, Trask AJ, Lin CH, Hans CP, Garg V, et al. MicroRNA miR145 regulates TGFBR2 expression and matrix synthesis in vascular smooth muscle cells. Circ Res 2015; 116(1): 23-34.
  37. Wang W, Chen L, Shang C, Jin Z, Yao F, Bai L, et al. miR-145 inhibits the proliferation and migration of vascular smooth muscle cells by regulating autophagy. J Cell Mol Med 2020; 24(12): 6658-69.
  38. He M, Wu N, Leong MC, Zhang W, Ye Z, Li R, et al. miR-145 improves metabolic inflammatory disease through multiple pathways. J Mol Cell Biol 2020; 12(2): 152-62.
  39. Faccini J, Ruidavets JB, Cordelier P, Martins F, Maoret JJ, Bongard V, et al. Circulating miR-155, miR-145 and let-7c as diagnostic biomarkers of the coronary artery disease. Sci Rep 2017; 7: 42916.
  40. Martinelli R, Nardelli C, Pilone V, Buonomo T, Liguori R, Castano I, et al. miR-519d overexpression is associated with human obesity. Obesity (Silver Spring) 2010; 18(11): 2170-6.
  41. Joseph AT, Bhardwaj SK, Srivastava LK. Role of prefrontal cortex anti- and pro-inflammatory cytokines in the development of abnormal behaviors induced by disconnection of the ventral hippocampus in neonate rats. Front Behav Neurosci 2018; 12: 244.
  42. Chu C, Liu X, Bai X, Zhao T, Wang M, Xu R, et al. MiR-519d suppresses breast cancer tumorigenesis and metastasis via targeting MMP3. Int J Biol Sci 2018; 14(2): 228-36.
  43. Gu W, Zhan H, Zhou XY, Yao L, Yan M, Chen A, et al. MicroRNA-22 regulates inflammation and angiogenesis via targeting VE-cadherin. FEBS Lett 2017; 591(3): 513-26.
  44. Xia Y, Chen Q, Zhong Z, Xu C, Wu C, Liu B, et al. Down-regulation of miR-30c promotes the invasion of non-small cell lung cancer by targeting MTA1. Cell Physiol Biochem 2013; 32(2): 476-85.
  45. Hua M, Qin Y, Sheng M, Cui X, Chen W, Zhong J, et al. miR145 suppresses ovarian cancer progression via modulation of cell growth and invasion by targeting CCND2 and E2F3. Mol Med Rep 2019; 19(5): 3575-83.
  46. Chen R, Zhou S, Chen J, Lin S, Ye F, Jiang P. LncRNA BLACAT1/miR-519d-3p/CREB1 axis mediates proliferation, apoptosis, migration, invasion, and drug-resistance in colorectal cancer progression. Cancer Manag Res 2020; 12: 13137-48.
  47. Lee JS, Ko EJ, Hwang HS, Lee YN, Kwon YM, Kim MC, et al. Antiviral activity of ginseng extract against respiratory syncytial virus infection. Int J Mol Med 2014; 34(1): 183-90.