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Levels of miR-130b-5p in peripheral blood are associated with severity of coronary artery disease

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Abstract

Background

Although patients with coronary artery disease (CAD) have a high mortality rate, the pathogenesis of CAD is still poorly understood. During the past decade, microRNAs (miRNAs) have emerged as new, potential diagnostic biomarkers in several diseases, including CAD. This study aimed to investigate the expression profiles of miRNAs in individuals with CAD and non-CAD.

Methods and results

The Agilent’s microarray analyses were performed to compare the whole blood miRNA profile of selected individuals with severe CAD (n = 12, ≥ 90% stenosis) and non-CAD (n = 12, ≤ 20 stenosis). Expressions of selected differentially expressed miRNAs (DEMs) were analyzed for validation in individuals with critical CAD (n = 50) and non-CAD (n = 43) using real-time PCR. Target prediction tools were utilized to identify miRNA target genes. We identified 6 DEMs that were downregulated in CAD patients, which included hsa-miR-18a-3p and hsa-miR-130b-5p, that were analyzed for further testing. Expression levels of hsa-miR-130b-5p were found negatively correlated with SYNTAX score and stenosis in female CAD patients (p < 0.05). In addition, both miRNAs were found positively correlated with plasma HDL and inversely correlated with fasting triglyceride levels (p < 0.05). In linear regression analysis adjusted for several confounders, the correlations have remained statistically significant. Computational prediction of target genes indicated a relevant role of hsa-miR-130b-5p and hsa-miR-18a-3p in modulating the expression of genes associated with cardiovascular diseases.

Conclusion

Our findings highlight a significantly different pattern of miRNA expression in CAD patients in microarray results. Hsa-miR-18a-3p and hsa-miR-130b-5p might serve as biomarkers of CAD development and progression and warrant further attention.

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References

  1. Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE Jr et al (2013) 2012 ACCF/AHA focused update incorporated into the ACCF/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 61(23):e179-347

    Article  PubMed  Google Scholar 

  2. He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5(7):522–531

    Article  CAS  PubMed  Google Scholar 

  3. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K et al (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18(10):997–1006

    Article  CAS  PubMed  Google Scholar 

  4. Gupta SK, Bang C, Thum T (2010) Circulating microRNAs as biomarkers and potential paracrine mediators of cardiovascular disease. Circ Cardiovasc Genet 3(5):484–488

    Article  CAS  PubMed  Google Scholar 

  5. Zhou SS, Jin JP, Wang JQ, Zhang ZG, Freedman JH, Zheng Y et al (2018) miRNAS in cardiovascular diseases: potential biomarkers, therapeutic targets and challenges. Acta Pharmacol Sin 39(7):1073–1084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Kaur A, Mackin ST, Schlosser K, Wong FL, Elharram M, Delles C et al (2020) Systematic review of microRNA biomarkers in acute coronary syndrome and stable coronary artery disease. Cardiovasc Res 116(6):1113–1124

    Article  CAS  PubMed  Google Scholar 

  7. Faccini J, Ruidavets JB, Cordelier P, Martins F, Maoret JJ, Bongard V et al (2017) Circulating miR-155, miR-145 and let-7c as diagnostic biomarkers of the coronary artery disease. Sci Rep 7:42916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Wang F, Long G, Zhao C, Li H, Chaugai S, Wang Y et al (2014) Atherosclerosis-related circulating miRNAs as novel and sensitive predictors for acute myocardial infarction. PLoS ONE 9(9):e105734

    Article  PubMed  PubMed Central  Google Scholar 

  9. Parizadeh SM, Ferns GA, Ghandehari M, Hassanian SM, Ghayour-Mobarhan M, Parizadeh SMR et al (2018) The diagnostic and prognostic value of circulating microRNAs in coronary artery disease: a novel approach to disease diagnosis of stable CAD and acute coronary syndrome. J Cell Physiol 233(9):6418–6424

    Article  CAS  PubMed  Google Scholar 

  10. Borghini A, Andreassi MG (2018) Genetic polymorphisms offer insight into the causal role of microRNA in coronary artery disease. Atherosclerosis 269:63–70

    Article  CAS  PubMed  Google Scholar 

  11. Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J et al (2010) Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 31(6):659–666

    Article  PubMed  Google Scholar 

  12. Mayr B, Niebauer J, Breitenbach-Koller H (2019) Circulating miRNAs as predictors for morbidity and mortality in coronary artery disease. Mol Biol Rep 46(5):5661–5665

    Article  CAS  PubMed  Google Scholar 

  13. Gensini GG (1983) A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 51(3):606

    Article  CAS  PubMed  Google Scholar 

  14. Serruys PW, Morice M-C, Kappetein AP, Colombo A, Holmes DR, Mack MJ et al (2009) Percutaneous coronary ıntervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 360(10):961–972

    Article  CAS  PubMed  Google Scholar 

  15. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M et al (2018) 2018 ESC/ESH Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens 36(10):1953–2041

    Article  CAS  PubMed  Google Scholar 

  16. Dweep H, Gretz N (2015) miRWalk2.0: a comprehensive atlas of microRNA-target interactions. Nat Methods 12(8):697

    Article  CAS  PubMed  Google Scholar 

  17. da Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57

    Article  CAS  Google Scholar 

  18. da Huang W, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37(1):1–13

    Article  Google Scholar 

  19. Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV et al (2013) Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinform 14:128

    Article  Google Scholar 

  20. Becker KG, Barnes KC, Bright TJ, Wang SA (2004) The genetic association database. Nat Genet 36(5):431–432

    Article  CAS  PubMed  Google Scholar 

  21. Rappaport N, Nativ N, Stelzer G, Twik M, Guan-Golan Y, Stein TI et al (2013) MalaCards: an integrated compendium for diseases and their annotation. Database (Oxford) 2013:bat018

    Article  Google Scholar 

  22. Rehmsmeier M, Steffen P, Hochsmann M, Giegerich R (2004) Fast and effective prediction of microRNA/target duplexes. RNA 10(10):1507–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G et al (2017) Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol 70(1):1–25

    Article  PubMed  PubMed Central  Google Scholar 

  24. Gao H, Guddeti RR, Matsuzawa Y, Liu LP, Su LX, Guo D et al (2015) Plasma levels of microRNA-145 are associated with severity of coronary artery disease. PLoS ONE 10(5):e0123477

    Article  PubMed  PubMed Central  Google Scholar 

  25. Gacon J, Kablak-Ziembicka A, Stepien E, Enguita FJ, Karch I, Derlaga B et al (2016) Decision-making microRNAs (miR-124, -133a/b, -34a and -134) in patients with occluded target vessel in acute coronary syndrome. Kardiol Pol 74(3):280–288

    Article  PubMed  Google Scholar 

  26. Mayer O Jr, Seidlerová J, Černá V, Kučerová A, Vaněk J, Karnosová P et al (2019) The low expression of circulating microRNA-19a represents an additional mortality risk in stable patients with vascular disease. Int J Cardiol 289:101–106

    Article  PubMed  Google Scholar 

  27. Huang W, Wu X, Xue Y, Zhou Y, Xiang H, Yang W et al (2021) MicroRNA-3614 regulates inflammatory response via targeting TRAF6-mediated MAPKs and NF-κB signaling in the epicardial adipose tissue with coronary artery disease. Int J Cardiol 324:152–164

    Article  PubMed  Google Scholar 

  28. Acharjee S, Boden WE, Hartigan PM, Teo KK, Maron DJ, Sedlis SP et al (2013) Low levels of high-density lipoprotein cholesterol and increased risk of cardiovascular events in stable ischemic heart disease patients: a post-hoc analysis from the COURAGE Trial (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation). J Am Coll Cardiol 62(20):1826–1833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB (1986) Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA 256(20):2835–2838

    Article  CAS  PubMed  Google Scholar 

  30. Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, Bingham S et al (2007) Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies. Circulation 115(4):450–458

    Article  CAS  PubMed  Google Scholar 

  31. Brunner D, Altman S, Loebl K, Schwartz S, Levin S (1977) Serum cholesterol and triglycerides in patients suffering from ischemic heart disease and in healthy subjects. Atherosclerosis 28(2):197–204

    Article  CAS  PubMed  Google Scholar 

  32. Moore KJ, Rayner KJ, Suarez Y, Fernandez-Hernando C (2010) microRNAs and cholesterol metabolism. Trends Endocrinol Metab 21(12):699–706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Qiu X-K, Ma J (2018) Alteration in microRNA-155 level correspond to severity of coronary heart disease. Scand J Clin Lab İnvestig 78(3):219–223

    Article  CAS  Google Scholar 

  34. Zhang Y, Li H-H, Yang R, Yang B-J, Gao Z-Y (2017) Association between circulating microRNA-208a and severity of coronary heart disease. Scand J Clin Lab Investig 77(5):379–384

    Article  CAS  Google Scholar 

  35. Cheng ZH, Luo C, Guo ZL (2019) MicroRNA-130b-5p accelerates the migration and invasion of osteosarcoma via binding to TIMP2. Eur Rev Med Pharmacol Sci 23(21):9267–9276

    PubMed  Google Scholar 

  36. Zhang N, Hu Z, Qiang Y, Zhu X (2019) Circulating miR-130b- and miR-21-based diagnostic markers and therapeutic targets for hepatocellular carcinoma. Mol Genet Genomic Med 7(12):e1012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhou XJ, Wang J, Ye HH, Fa YZ (2019) Signature MicroRNA expression profile is associated with lipid metabolism in African green monkey. Lipids Health Dis 18(1):55

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kosmopoulos M, Paschou SA, Grapsa J, Anagnostis P, Vryonidou A, Goulis DG et al (2019) The emerging role of bone markers in diagnosis and risk stratification of patients with coronary artery disease. Angiology 70(8):690–700

    Article  CAS  PubMed  Google Scholar 

  39. Bennett BJ, Scatena M, Kirk EA, Rattazzi M, Varon RM, Averill M et al (2006) Osteoprotegerin inactivation accelerates advanced atherosclerotic lesion progression and calcification in older ApoE-/- mice. Arterioscler Thromb Vasc Biol 26(9):2117–2124

    Article  CAS  PubMed  Google Scholar 

  40. Chiba S, Okamoto H, Kon S, Kimura C, Murakami M, Inobe M et al (2002) Development of atherosclerosis in osteopontin transgenic mice. Heart Vessels 16(3):111–117

    Article  PubMed  Google Scholar 

  41. Tousoulis D, Siasos G, Maniatis K, Oikonomou E, Kioufis S, Zaromitidou M et al (2013) Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease. Int J Cardiol 167(5):1924–1928

    Article  PubMed  Google Scholar 

  42. Momiyama Y, Ohmori R, Fayad ZA, Kihara T, Tanaka N, Kato R et al (2010) Associations between plasma osteopontin levels and the severities of coronary and aortic atherosclerosis. Atherosclerosis 210(2):668–670

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Abdel-Azeez HA, Al-Zaky M (2010) Plasma osteopontin as a predictor of coronary artery disease: association with echocardiographic characteristics of atherosclerosis. J Clin Lab Anal 24(3):201–206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Brew K, Nagase H (2010) The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity. Biochim Biophys Acta 1803(1):55–71

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Han Y, Joo HJ, Seo HR, Choi SC, Park JH, Yu CW et al (2016) Serum TIMP-2, NGAL and angiopoietin-2 as biomarkers of coronary artery stenosis. Int J Clin Exp Med 9(7):14141–14149

    CAS  Google Scholar 

  46. Tayebjee MH, Lip GY, Tan KT, Patel JV, Hughes EA, MacFadyen RJ (2005) Plasma matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-2, and CD40 ligand levels in patients with stable coronary artery disease. Am J Cardiol 96(3):339–345

    Article  CAS  PubMed  Google Scholar 

  47. Liu F, Li R, Zhang Y, Qiu J, Ling W (2014) Association of plasma MiR-17–92 with dyslipidemia in patients with coronary artery disease. Medicine (Baltimore) 93(23):e98

    Article  CAS  Google Scholar 

  48. Vacca M, Di Eusanio M, Cariello M, Graziano G, D’Amore S, Petridis FD et al (2016) Integrative miRNA and whole-genome analyses of epicardial adipose tissue in patients with coronary atherosclerosis. Cardiovasc Res 109(2):228–239

    Article  CAS  PubMed  Google Scholar 

  49. Kim SH, Yun SJ, Kim YH, Ha JM, Jin SY, Lee HS et al (2015) Essential role of kruppel-like factor 5 during tumor necrosis factor alpha-induced phenotypic conversion of vascular smooth muscle cells. Biochem Biophys Res Commun 463(4):1323–1327

    Article  CAS  PubMed  Google Scholar 

  50. Srivastava R, Zhang J, Go GW, Narayanan A, Nottoli TP, Mani A (2015) Impaired LRP6-TCF7L2 activity enhances smooth muscle cell plasticity and causes coronary artery disease. Cell Rep 13(4):746–759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zhang YN, Xie BD, Sun L, Chen W, Jiang SL, Liu W et al (2016) Phenotypic switching of vascular smooth muscle cells in the “normal region” of aorta from atherosclerosis patients is regulated by miR-145. J Cell Mol Med 20(6):1049–1061

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Helwak A, Kudla G, Dudnakova T, Tollervey D (2013) Mapping the human miRNA interactome by CLASH reveals frequent noncanonical binding. Cell 153(3):654–665

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ishikawa Y, Akasaka Y, Ishii T, Komiyama K, Masuda S, Asuwa N et al (1998) Distribution and synthesis of apolipoprotein J in the atherosclerotic aorta. Arterioscler Thromb Vasc Biol 18(4):665–672

    Article  CAS  PubMed  Google Scholar 

  54. Zhu H, Liu M, Zhai T, Pan H, Wang L, Yang H et al (2019) High serum clusterin levels are associated with premature coronary artery disease in a Chinese population. Diabetes Metab Res Rev 35(4):e3128

    Article  PubMed  Google Scholar 

  55. Mackness B, Hunt R, Durrington PN, Mackness MI (1997) Increased immunolocalization of paraoxonase, clusterin, and apolipoprotein A-I in the human artery wall with the progression of atherosclerosis. Arterioscler Thromb Vasc Biol 17(7):1233–1238

    Article  CAS  PubMed  Google Scholar 

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Funding

This study was supported by The Research Support Unit of Istanbul University as Project No: 25943.

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Authors and Affiliations

Authors

Contributions

NC: Conceptualization, methodology, investigation, resources, writing-original draft, writing—review & editing, supervision, project administration, funding acquisition ASO: Formal analysis, investigation, writing-original draft, writing—review & editing, visualization AFE: Methodology, investigation, resources, writing—review & editing FG: Investigation, writing—review & editing, methodology BE: Investigation, resources, writing—review & editing.

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Correspondence to Neslihan Coban.

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Whole sample collection and analysis processes were conducted in compliance with the ethical guidelines of the Declaration of Helsinki and approved by the Institutional Review Board at Istanbul University.

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The written informed consent was obtained from all participants, and all experiments were performed following the approved guidelines and regulations.

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Coban, N., Ozuynuk, A.S., Erkan, A.F. et al. Levels of miR-130b-5p in peripheral blood are associated with severity of coronary artery disease. Mol Biol Rep 48, 7719–7732 (2021). https://doi.org/10.1007/s11033-021-06780-5

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