Diagnostic value of micro-RNAs for coronary artery disease in Egyptian type 2 diabetic patients

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Research Paper 01/11/2020
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Diagnostic value of micro-RNAs for coronary artery disease in Egyptian type 2 diabetic patients

Mai S. Esmail, Said S. Farkouh, Magda K. Ezz, Eman M. Abd El Azeem
Int. J. Biosci.17( 5), 11-22, November 2020.
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With an increasing global burden of coronary artery disease (CAD), early detection and timely management of risk factors are crucial to reduce morbidity and mortality in such patients. Diabetes mellitus (DM) is considered an independent risk factor for the development of CAD. Circulating microRNAs have been recognized as promising biomarkers for various diseases. The present study aimed to explore the potential role of circulating miRNA-149, mi-RNA424 and mi-RNA765 as non-invasive biomarkers for the diagnosis of coronary artery disease in middle-aged (40–60-years old) type 2 diabetes mellitus patients. This study included 120 volunteers of both sexes classified as group I: 30 normal subjects; group II: 30 type 2 diabetic patients (T2D), group III: 30 coronary artery disease patients (CAD) and group IV 30 type 2 diabetic patients with coronary artery disease (T2D&CAD). Plasma mi-RNAs, diabetic biomarkers, lipid profile, inflammatory biomarkers and troponin I were determined. Circulating mi-RNA765 levels were elevated in T2DM with CAD group (7.04 ±0.36), compared with T2DM group (2.01 ±0.27). In contrast, circulating mi-RNA149 and mi-RNA424 levels were decreased in T2DM with CAD group (0.9 ±0.09 &0.84±0.08), compared with T2DM group (4.28 ±0.32 & 4.52 ±0.31) respectively. These results suggest that circulating mi-RNA149, mi-RNA 424 and mi-RNA765 might be non-invasive biomarkers for the diagnosis of coronary artery disease in middle-aged diabetic patients.


Ali Sheikh MS, Xia K, Li F, Deng X, Salma U, Deng H. 2015. Circulating miR-765 and miR-149: potential noninvasive diagnostic biomarkers for geriatric coronary artery disease patients. Biomed Research International 740301.

Al-Jameil N, Khan F, Arjumand S, Khan M, Tabassum H. 2014. Dyslipidemia and its correlation with type 2 diabetic patients at different stages of proteinuria. Biomed Research India 25, 227-231.

Badimon L, Padró T, Vilahur G. 2012 Atherosclerosis, platelets and thrombosis in acute ischaemic heart disease. European Heart Journal Acute Cardiovascular Care 1, 60-74.

Balakumar P., Maung UK., Jagadeesh G. 2016. Prevalence and prevention of cardiovascular disease and diabetes mellitus. Pharmacol Research 113, 600– 9. http://dx.doi.org/10.1016/j.phrs.09.040.

Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G. 2004. Population-based incidence rates and risk factors for type 2 daibetes in white individuals: the Bruneck study. Diabetes 53, 1782-9.

Chatzigeorgiou A, Lyberi M, Chatzilymperis, G, Nezos A, Kamper E. 2009. CD40/CD40L signaling and its implication in health and disease. Biofactors 35, 474–483, http://dx.doi.org/10.1002/biof.62.

Coimbra S, Proenca JB, Silva AS, Neuparth MJ. 2014. Adiponectin, leptin and chemerin in elderly patients with type 2 diabetes mellitus: a close linkage with obesity and length of disease. Biomed Research International, 1-8.

Da Costa Martins PA, Salic K, Gladka MM, Armand AS, Leptidis S, Azzouzi H. 2010. MicroRNA- 199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signaling. Nature cell biology 12: 1220–1227. PMID:21102440. http://dx.doi.org/10.1038/ncb2126

Ding L, Su XX, Zhang WH, Xu YX, Pan XF. 2017. Gene Expressions Underlying Mishandled Calcium Clearance and Elevated Generation of Reactive Oxygen Species in the Coronary Artery Smooth Muscle Cells of Chronic Heart Failure Rats. Chinese Medical Journal (Engl) 130, 460-469.

Eggers KM, Al-Shakarchi J, Berglund L, Lindahl B, Siegbahn A, Wallentin L. 2013. High-sensitive cardiac troponin T and its relations to cardiovascular risk factors, morbidity, and mortality in elderly men. American Heart Journal 166(3), 541–8.

Feinberg MW, Moore KJ. 2016. MicroRNA Regulation of Atherosclerosis. Circulation Research 118, 703-720.

Flier JS, Kahn CR, Roth J. 1979. Receptors, anti- receptors antibodies and mechanism of insulin resistance. The New England Journal of Medicine 300(8), 413-419.

Friedewald W, Levy RI, Fredrickson DS. 1972. Evaluation of Insulin Resistance Indices in Type 2 Diabetic patients Treated with Different Anti-Diabetic Drugs. Open Journal of Endocrine and Metabolic Diseases 6, 95-101.

Gupta SK, Bang C, Thum T. 2010. Circulating microRNAs as biomarkers and potential paracrine mediators of cardiovascular disease. Circulating cardiovascular Genet 3(5), 484-8.

Hoekstra M, van der Lans CA, Halvorsen B. 2010. The peripheral blood mononuclear cell microRNA signature of coronary artery disease. Biochem Biophys Res Commun 394, 792-7. http://dx.doi.org/10.1016/j.bbrc.2010.03.075.

Hou H, Wang C, Sun F, Zhao L, Dun A, Sun Z. 2015. Association of interleukin-6 gene polymorphism with coronary artery disease: an updated systematic review and cumulative meta-analysis. Inflammation Research 64(9), 707–20.

Huo X, Gao L, Guo L, Xu W, Wang W, Zhi X. 2016. Risk of non-fatal cardiovascular diseases in early-onset versus late-onset type 2 diabetes in China: a cross-sectional study. Lancet Diabetes Endocrinol 4, 115–24. http://dx.doi.org/10.1016/S2213-8587(15)00508-2.

International Diabetes Federation. 2017. Diabetes atlas. 8th ed. Brussels: International Diabetes Federation.

Jansen F, Yang X, Proebsting S, Hoelscher M, Przybilla D, Baumann K. 2014. MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease. Journal of the American Heart Association 3, e001249.

Jessica A, Weber DHB, Shile Zhang, David Y, Huang. Kuo How Huang, Ming Jen Lee, David J, Galas Kai Wang. 2010. The MicroRNA Spectrum

in Body Fluids. Clinical Chemistry 56(11), 1733-41.

Kanwar G, Jain N, Sharma N, Shekhawat M, Ahmed J. 2015. Significance of serum Urea and Creatinine Levels in Type 2 Diabetic Patients. (IOSR- JDMS). 14, 65-7.

Kaplan A. 1984. Triglycerides. Clin Chem. The C.V.  Mosby Co. St Louis. Toronto. Princeton, 437 and  lipids 1149-1206.

Kim J. 2014. Apelin-APJ signaling: a potential therapeutic target for pulmonary arterial hypertension. Molecules and Cells 37, 196–201.

Kumar R, Abbas A, Fausto N, Aster J. 2010. “Pathologic basis   of disease” 8th Ed. Saunders Elsevier Publishing Division. 934-935, 1131-1146.

Lee A. 2014. Therapeutic implications of microRNAs in pulmonary arterial hypertension. BMB reports 47, 311–317, http://dx.doi.org/10.5483/BMBRep.2014.47.6.085.

Lee A, Papangeli I, Park Y, Jeong HN, Choi J, Kang H. 2017. A PPARgamma-dependent miR-424/503-CD40 axis regulates inflammation mediated angiogenesis. Scientific Reports 7, 2528.

Lloyd-Jones DM, Braun LT, Ndumele CE, Smith SC Jr., Sperling LS, Virani SS, Blumenthal RS. 2018. Use of risk assessment tools to guide decision-making in the primary prevention of atherosclerotic cardiovascular disease: a special report from the American Heart Association and American College of Cardiology. Journal of the American College of Cardiology 2018. Https://doi.org/10.1016/j.jacc.11.005.

Lopes Virella MF. 1977. Clin. Chem. 23: 882. Luo., Fei Luo., Avash Das., Jingfei Chen., Panyun Wu, Xiangping Li and Zhenfei Fang 2019. Cardiovasc Diabetol 18, 54. https://doi.org/10.1186/s12933-019-0860.

Matsuzawa Y, Lerman A. 2014. Endothelial dysfunction and coronary artery disease: assessment, prognosis, and treatment. Coronary Artery Disease, 25, 713-724.

Murray R, Kaplan A. 1984. Alanine aminotransferase, Clin Chem the C.V. Mosby Co. St Louis. Toronoto. Princeton, 1088-1090.

Murray R, Kaplan A. 1984. Aspartate aminotransferase. Clin Chem. The C.V. Mosby Co. St Louis. Toronoto. Princeton, 1112-116.

Naito HK, Kaplan A, Clin Chem. 1984. The C.V. Mosby Co. St Louis. Toronoto. Princeton, 1194-11206 and 437.

Novak J, Olejnickova V, Tkacova N, Santulli G. 2015. Mechanistic Role of MicroRNAs in Coupling Lipid Metabolism and Atherosclerosis. Advances in Experimental Medicine and Biology 887, 79-100.

Nurnberg ST, Cheng K, Raiesdana A, Kundu R, Miller CL, Kim JB. 2015. Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap. PLoS Genet, 11, e1005155.

Omari KM, Dorovini-Zis K. 2003. CD40 expressed by human brain endothelial cells regulates CD4+ T cell adhesion to endothelium.

Pacher P, Beckman JS, Liaudet L. 2007. Nitric oxide and peroxynitrite in health and disease. Physiological Reviews 87, 315-424.

Pinto A, Tuttolomondo A, Casuccio A, Raimondo DI, Sciacca DI, Valentina A, Giuseppe L. 2009. Immuno-inflammatory predictors of stroke at follow-up in patients with chronic non-valvular atrial fibrillation (NVAF). Clinical Science 116, 781-789.

Qu HQ, Quan L, Anne RR, Susan P, McCormick FH, Joseph B. 2011. The definition of insulin resistance using HOMA-IR for Americans of Mexican Descent using machine learning. Plos One; 6(6), e21041.

Ren J, Zhang J, Xu N. 2013. Signature of circulating microRNAs as potential biomarkers in vulnerable coronary artery disease. PLoS One. 8. http://dx.doi.org/10.1371/journal.pone.0080738.

Sayed ASM, Xia K, Li F. 2015. Circulating miR-765 and miR-149: potential noninvasive diagnostic biomarkers for geriatric coronary artery disease patients. BioMed Research International 1-8. http://dx.doi.org/10.1155/2015/740301.

Schiattarella GG, Altamirano F, Tong D, French KM, Villalobos E, Kim SY. 2019.  Nitrosative stress drives heart failure with preserved ejection fraction. Nature 568, 351–6. http://dx.doi.org/10.1038/s41586-019-1100-z

Shirai T, Nafarewicz RR, Wallis BB. 2016. The glycolytic enzyme PKM2 bridges metabolic and inflammatory dysfunction in coronary artery disease. J Exp Med.213:337–54 stiffness and hypertension. Journal of Cardiovascular Translational Research 5, 264–273.

Shu J, Matarese A, Santulli G. 2019.  Diabetes, body fat, skeletal muscle, and hypertension: The ominous chiasmus? Journal of Clinical Hypertension 21, 239–42. http://dx.doi.org/10.1111/jch.13453.

Shu J, Santulli G. 2018. Update on peripheral artery disease: epidemiology and evidence-based facts. Atherosclerosis 275, 379–81. http://dx.doi.org/10.1016/j.atherosclerosis.05.033.

Su D, Li Z, Li X, Chen Y. Association between serum interleukin-6 concentration and mortality in patients with coronary artery disease. Mediators of Inflammation 726178.

Taha D, Umpaichitra V, Baner Ji M, Castells S. 2006. Type 2 diabetes mellitus in African-American adolescent: impaired beta – cell function in the face of

sever insulin resistance. Journal of Pediatric Endocrinology and Metabolism 19, 135-142.

Takahashi M. 1996. Use of immunoassay for measurement of skeletal troponin-I utilizing isoform specific monoclonal antibodies. Clinical Biochemistry 29(4), 301-308.

Tousoulis D, Kampoli AM, Tentolouris C,  Papageorgiou N, Stefanadis C. 2012. The role of nitric oxide on endothelial function. Curr Vasc Pharmacol 10, 4-18.

Trinder P. 1969. Determination of blood glucose using 4-amino phenazone. Journal of Clinical Pathology 22(2), 246.

Trivelli LA, Ranney HM, Lai HT. 1971. Hemoglobine components in patients with diabetic mellitus. The New England Journal of Medicine 284, 353-357.

Van Rooij E, Sutherland LB, Thatcher JE, DiMaio JM, Naseem RH, Marshall WS. 2008. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis. Proceedings of the National Academy of Sciences of the United States of America 105(35), 13027-32. http://dx.doi.org/10.1073/pans.0805038105.

Wagschal A, Najafi-Shoushtari SH, Wang L, Goedeke L, Sinha S, deLemos AS. 2015. Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis. Nature Medicine 21, 1290-1297.

Wang YY, Lin S Y, Liu PH, Cheuug BM, Lai WA. 2004. Association between hematological parameters and metabolic syndrome components in a chinese population. Journal of Diabetes and its Complications 18, 322-327.

Wu Y, Gong A, Sun. 2013. “The human MTHFR rs4846049 polymorphism increases coronary heart disease risk through modifying miRNA binding,” Nutrition, Metabolism and Cardiovascular Diseases 23(7), p 693–698.

Xu G, Zhang Z, Xing Y, Wei J, Ge Z, Liu X. 2014. MicroRNA-149 nega-tively regulates TLR-triggered inflammatory response in macrophages by targeting MyD88. Cell Biochemistry 115, 919–27. http://dx.doi.org/10.1002/jcb.24734.

Yang L. 2012. SIRT1 regulates CD40 expression induced by TNF-alpha via NF-kB pathway in endothelial cells. Cellular Physiology and Biochemistry.

Zhu GF, Yang LX, Guo RW. 2014. MicroRNA-155 is inversely associated with severity of coronary stenotic lesions calculated by the Gensini score. Coronary Artery Disease 25, 304-10. http://dx.doi.org/10.1097/MCA.