A study on circulating micro RNAs in Egyptian diabetic patients with/without risk of cardiovascular complications
DOI:
https://doi.org/10.56511/JIPBS.2016.v3.i04.pp43-48Abstract
Egypt is ranked number nine among the top 10 countries of people with diabetes. The long term macro and microvascular diabetic complications are responsible for the diabetes- associated mortality. Thus, improving the quality of diabetic patients’ life requires early prediction and prevention of chronic diabetic complications. Recently, microRNAs (miRNAs), which are short RNA molecules acting as regulators of protein expression in eukaryotic cells, had a great attention as novel potential biomarkers in several diseases. The objective of the current study was to evaluate serum levels of miR-126, mi-R133, miR-96 and miR-93 in Egyptian T2DM patients with/without cardiovascular complications. The present study compromised 18 healthy controls and 53 Egyptian diabetic patients divided into: 13 diabetic patients without diabetic cardiovascular complications and 40 patients with risk for diabetic cardiovascular complications. The expression levels of mature miRNAs were detected in all patients and controls sera using quantitative RT- PCR. Serum levels of miR-133, miR-126 and miR-93 were significantly reduced while serum miR-96 was significantly increased in T2DM patients without risk for cardiovascular complications compared to the healthy controls, which may play a role in developing diabetes and differentiating patients with a high likelihood of developing diabetes from healthy controls. Moreover, there was a significant decrease in miR-133 and miR-126 levels between the two diabetic groups, which suggests that both miRNAs could be useful for prediction of cardiovascular disease in T2DM Egyptian patients.
Keywords:
Cardiovascular complications, miR-93, miR-96, miR-126, miR-133, T2DMDownloads
References
Guariguata L: Contribute data to the 6th edition of the IDF Diabetes Atlas. Diabetes research and clinical practice 2013; 100(2):280-281.
American Diabetes Association: Diagnosis and classification of diabetes. Diabetes Care 201; 36:67-74.
Rubler S, Dlugash J, Yuceoglu YZ, Kumral T, Branwood AW, Grishman A: New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol 1972; 30(6):595-602.
Fein FS, Sonnenblick EH: Diabetic cardiomyopathy. Cardiovasc Drugs Ther 1994; 8(1):65-73.
Rahangdale S, Yeh SY, Malhotra A, Veves A: Therapeutic interventions and oxidative stress in diabetes. Front Biosci (Landmark Ed) 2009; 14:192209.
Sebastiani G, Nigi L, Spagnuolo I, Morganti E, Fondelli C, Dotta F: MicroRNA profiling in sera of patients with type 2 diabetes mellitus reveals an upregulation of miR-31 expression in subjects with microvascular complications. J Biomedical Science and Engineering 2013; 6:58-64.
Fabian MR, Sonenberg N, Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Annual review of biochemistry 2010; 79:351379.
Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 2004; 116(2):281-297.
Diao X, Shen E, Wang X, Hu B: Differentially expressed microRNAs and their target genes in the hearts of streptozotocin-induced diabetic mice. Mol Med Rep 2011; 4(4):633-640.
Wang XH, Qian RZ, Zhang W, Chen SF, Jin HM, Hu RM: MicroRNA-320 expression in myocardial microvascular endothelial cells and its relationship with insulin-like growth factor-1 in type 2 diabetic rats. Clin Exp Pharmacol Physiol 2009; 36(2):181-188.
Jeong HJ, Park SY, Yang WM, Lee W: The induction of miR-96 by mitochondrial dysfunction causes impaired glycogen synthesis through translational repression of IRS-1 in SK-Hep1 cells. Biochem Biophys Res Commun 2013; 434(3):503-508.
Lovis P, Gattesco S, Regazzi R: Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs. Biol Chem 2008; 389(3):305-312.
Feng B, Chen S, George B, Feng Q, Chakrabarti S: miR133a regulates cardiomyocyte hypertrophy in diabetes. Diabetes Metab Res Rev 2010; 26(1):40-49.
Goren Y, Kushnir M, Zafrir B, Tabak S, Lewis BS, Amir O: Serum levels of microRNAs in patients with heart failure. Eur J Heart Fail 2012; 14(2):147154.
Martin-Gallan P, Carrascosa A, Gussinye M, Dominguez C: Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications. Free Radic Biol Med 2003; 34(12):1563-1574.
Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, Richardson JA, Bassel-Duby R, Olson EN: The endothelial-specific microRNA miR126 governs vascular integrity and angiogenesis. Dev Cell 2008; 15(2):261271.
Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Kinoshita M, Watanabe S, Baba O, Kojima Y, Shizuta S et al: Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage. Circ Cardiovasc Genet 2011; 4(4):446-454.
Care A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, Bang ML, Segnalini P, Gu Y, Dalton ND et al: MicroRNA-133 controls cardiac hypertrophy. Nat Med 2007; 13(5):613-618.
Horie T, Ono K, Nishi H, Iwanaga Y, Nagao K, Kinoshita M, Kuwabara Y, Takanabe R, Hasegawa K, Kita T et al: MicroRNA-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiac myocytes. Biochem Biophys Res Commun 2009; 389(2):315-320.
Long J, Wang Y, Wang W, Chang BH, Danesh FR: Identification of microRNA-93 as a novel regulator of vascular endothelial growth factor in hyperglycemic conditions. J Biol Chem 2010; 285(30):23457-23465.
American Diabetes Association: Diagnosis and classification of diabetes mellitus. Diabetes Care 2011; 34 Suppl 1:S62-69.
Kunst A, Draeger B, Ziegenhorn J: UV-methods with hexokinase and glucose-6-phosphate dehydrogenase. 6 edn; 1983.
Jeppsson JO, Jerntorp P, Sundkvist G, Englund H, Nylund V: Measurement of hemoglobin A1c by a new liquid-chromatographic assay: methodology, clinical utility, and relation to glucose tolerance evaluated. Clin Chem 1986; 32(10):1867-1872.
Brinkman JW, Bakker SJ, Gansevoort RT, Hillege HL, Kema IP, Gans RO, de Jong PE, de Zeeuw D: Which method for quantifying urinary albumin excretion gives what outcome? A comparison of immunonephelometry with HPLC. Kidney international Supplement 2004; (92):S69-75.
Larsen K: Creatinine assay by a reaction-kinetic principle. Clinica chimica acta; international journal of clinical chemistry 1972; 41:209-217.
Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25(4):402-408.
Xiao J, Luo X, Lin H, Zhang Y, Lu Y, Wang N, Zhang Y, Yang B, Wang Z: MicroRNA miR-133 represses HERG K+ channel expression contributing to QT prolongation in diabetic hearts. J Biol Chem 2007; 282(17):1236312367.
Nakhjavani M, Esteghamati AR, Esfahanian F, AR H: Dyslipidemia in type 2 diabetes mellitus.More atherogenic lipid profile in women. . Acta Med Iranica 2006; 44:111-118.
Kanaya AM, Grady D, Barrett-Connor E: Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus: a meta-analysis. Arch Intern Med 2002; 162(15):1737-1745.
Barrett-Connor E, Giardina EG, Gitt AK, Gudat U, Steinberg HO, Tschoepe D: Women and heart disease: the role of diabetes and hyperglycemia. Arch Intern Med 2004; 164(9):934-942.
Karalliedde J, Viberti G: Microalbuminuria and cardiovascular risk. Am J Hypertens 2004; 17(10):986-993.
Kroh EM, Parkin RK, Mitchell PS, Tewari M: Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods 2010; 50(4):298-301.
Mraz M, Malinova K, Mayer J, Pospisilova S: MicroRNA isolation and stability in stored RNA samples. Biochem Biophys Res Commun 2009; 390(1):1-4.
Guay C, Regazzi R: Circulating microRNAs as novel biomarkers for diabetes mellitus. Nat Rev Endocrinol 2013; 9(9):513-521.
Ferland-McCollough D, Ozanne SE, Siddle K, Willis AE, Bushell M: The involvement of microRNAs in Type 2 diabetes. Biochem Soc Trans 2010; 38(6):1565-1570.
Erener S, Mojibian M, Fox JK, Denroche HC, Kieffer TJ: Circulating miR375 as a biomarker of beta-cell death and diabetes in mice. Endocrinology 2013; 154(2):603-608.
Kantharidis P, Wang B, Carew RM, Lan HY: Diabetes complications: the microRNA perspective. Diabetes 2011; 60(7):1832-1837.
Mishra PK, Tyagi N, Kumar M, Tyagi SC: MicroRNAs as a therapeutic target for cardiovascular diseases. J Cell Mol Med 2009; 13(4):778-789.
Gallagher IJ, Scheele C, Keller P, Nielsen AR, Remenyi J, Fischer CP, Roder K, Babraj J, Wahlestedt C, Hutvagner G et al: Integration of microRNA changes in vivo identifies novel molecular features of muscle insulin resistance in type 2 diabetes. Genome Med 2010; 2(2):9.
Zhang T, Li L, Shang Q, Lv C, Wang C, Su B: Circulating miR-126 is a potential biomarker to predict the onset of type 2 diabetes mellitus in susceptible individuals. Biochem Biophys Res Commun 2015; 463(1-2):6063.
Zhang T, Lv C, Li L, Chen S, Liu S, Wang C, Su B: Plasma miR-126 Is a Potential Biomarker for Early Prediction of Type 2 Diabetes Mellitus in Susceptible Individuals. BioMed Research International 2013; 2013:6.
Zampetaki A, Willeit P, Tilling L, Drozdov I, Prokopi M, Renard JM, Mayr A, Weger S, Schett G, Shah A et al: Prospective study on circulating MicroRNAs and risk of myocardial infarction. J Am Coll Cardiol 2012; 60(4):290-299.
Salas-Perez F, Codner E, Valencia E, Pizarro C, Carrasco E, Perez-Bravo F: MicroRNAs miR-21a and miR-93 are down regulated in peripheral blood mononuclear cells (PBMCs) from patients with type 1 diabetes. Immunobiology 2013; 218(5):733-737.
Ryu HS, Park SY, Ma D, Zhang J, Lee W: The induction of microRNA targeting IRS-1 is involved in the development of insulin resistance under conditions of mitochondrial dysfunction in hepatocytes. PLoS One 2011; 6(3):e17343.
Published
How to Cite
Issue
Section
Copyright (c) 2016 Shahenda Mahgoub, Heba Taha
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Journal of Innovations in Pharmaceutical and Biological Sciences is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Based on a work at