Top

Published in:

Open Access 01-12-2019 | Insulins | Review

Significance of circulating microRNAs in diabetes mellitus type 2 and platelet reactivity: bioinformatic analysis and review

Authors: Justyna Pordzik, Daniel Jakubik, Joanna Jarosz-Popek, Zofia Wicik, Ceren Eyileten, Salvatore De Rosa, Ciro Indolfi, Jolanta M. Siller-Matula, Pamela Czajka, Marek Postula

Published in: Cardiovascular Diabetology | Issue 1/2019

Abstract

In the light of growing global epidemic of type 2 diabetes mellitus (T2DM), significant efforts are made to discover next-generation biomarkers for early detection of the disease. Multiple mechanisms including inflammatory response, abnormal insulin secretion and glucose metabolism contribute to the development of T2DM. Platelet activation, on the other hand, is known to be one of the underlying mechanisms of atherosclerosis, which is a common T2DM complication that frequently results in ischemic events at later stages of the disease. Available data suggest that platelets contain large amounts of microRNAs (miRNAs) that are found in circulating body fluids, including the blood. Since miRNAs have been illustrated to play an important role in metabolic homeostasis through regulation of multiple genes, they attracted substantial scientific interest as diagnostic and prognostic biomarkers in T2DM. Various miRNAs, as well as their target genes are implicated in the complex pathophysiology of T2DM. This article will first review the different miRNAs studied in the context of T2DM and platelet reactivity, and subsequently present original results from bioinformatic analyses of published reports, identifying a common gene (PRKAR1A) linked to glucose metabolism, blood coagulation and insulin signalling and targeted by miRNAs in T2DM. Moreover, miRNA–target gene interaction networks built upon Gene Ontology information from electronic databases were developed. According to our results, miR-30a-5p, miR-30d-5p and miR-30c-5p are the most widely regulated miRNAs across all specified ontologies, hence they are the most promising biomarkers of T2DM to be investigated in future clinical studies.

Available only for authorised users

IDF Diabetes Atlas 6th Edition. Brussels: International Diabetes Federation; 2013. https://www.idf.org/e-library/epidemiology-research/diabetes-atlas/19-atlas-6th-edition.html. Accessed 12th December 2018.

Zimmet PZ. Diabetes and its drivers: the largest epidemic in human history? Clin Diabetes Endocrinol. 2017;18(3):1. https://doi.org/10.1186/s40842-016-0039-3.CrossRef

Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet. 2005;365(9467):1333–46. https://doi.org/10.1016/s0140-6736(05)61032-x.CrossRefPubMed

Zimmet PZ, Magliano DJ, Herman WH, Shaw JE. Diabetes: a 21st century challenge. Lancet Diabetes Endocrinol. 2014;2(1):56–64. https://doi.org/10.1016/S2213-8587(13)70112-8.CrossRefPubMed

Vaidya V, Gangan N, Sheehan J. Impact of cardiovascular complications among patients with Type 2 diabetes mellitus: a systematic review. Expert Rev Pharmacoecon Outcomes Res. 2015;15(3):487–97. https://doi.org/10.1586/14737167.2015.1024661.CrossRefPubMed

Wu MD, Atkinson TM, Lindner JR. Platelets and von Willebrand factor in atherogenesis. Blood. 2017;129(11):1415–9. https://doi.org/10.1182/blood-2016-07-692673.CrossRefPubMedPubMedCentral

Natarajan A, Zaman AG, Marshall SM. Platelet hyperactivity in type 2 diabetes: role of antiplatelet agents. Diabetes Vasc Dis Res. 2008;5:138–44. https://doi.org/10.3132/dvdr.2008.023.CrossRef

Ferroni P, Basili S, Falco A, et al. Platelet activation in type 2 diabetes mellitus. J Thromb Haemost. 2004;2:1282–91. https://doi.org/10.1111/j.1538-7836.2004.00836.x.CrossRefPubMed

Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259(5091):87–91.CrossRefPubMed

10.

Xia C, Rao X, Zhong J. Role of T lymphocytes in type 2 diabetes and diabetes-associated inflammation. J Diabetes Res. 2017;2017:6494795. https://doi.org/10.1155/2017/6494795.CrossRefPubMedPubMedCentral

11.

Nagy B Jr, Csongrádi E, Bhattoa HP, et al. Investigation of Thr715Pro P-selectin gene polymorphism and soluble P-selectin levels in type 2 diabetes mellitus. Thromb Haemost. 2007;98:186–91.CrossRefPubMed

12.

Postula M, Kaplon-Cieslicka A, Rosiak M, Kondracka A, Serafin A, Filipiak KJ, Czlonkowski A, Opolski G, Janicki PK. Genetic determinants of platelet reactivity during acetylsalicylic acid therapy in diabetic patients: evaluation of 27 polymorphisms within candidate genes. J Thromb Haemost. 2011;9(11):2291–301. https://doi.org/10.1111/j.1538-7836.2011.04482.x.CrossRefPubMed

13.

Kim SJ, Davis RP, Jenne CN. Platelets as modulators of inflammation. Semin Thromb Hemost. 2018;44(2):91–101. https://doi.org/10.1055/s-0037-1607432.CrossRefPubMed

14.

Cortez-Espinosa N, Mayoral LP, Perez-Campos E, Cabrera Fuentes HA, Mayoral EP, Martínez-Cruz R, Canseco SP, Andrade GM, Cruz MM, Velasco IG, Cruz PH. Platelets and platelet-derived microvesicles as immune effectors in type 2 diabetes. Curr Vasc Pharmacol. 2017;15(3):207–17. https://doi.org/10.2174/1570161115666170126130309.CrossRefPubMed

15.

Nielsen CT, Østergaard O, Rasmussen NS, Jacobsen S, Heegaard NHH. A review of studies of the proteomes of circulating microparticles: key roles for galectin-3-binding protein-expressing microparticles in vascular diseases and systemic lupus erythematosus. Clin Proteom. 2017;8(14):11. https://doi.org/10.1186/s12014-017-9146-0.CrossRef

16.

Dangwal S, Thum T. MicroRNAs in platelet biogenesis and function. Thromb Haemost. 2012;108:599–604. https://doi.org/10.1160/TH12-03-0211.CrossRefPubMed

17.

Eyileten C, Wicik Z, De Rosa S, Mirowska-Guzel D, Soplinska A, Indolfi C, Jastrzebska-Kurkowska I, Czlonkowska A, Postula M. MicroRNAs as diagnostic and prognostic biomarkers in ischemic stroke—a comprehensive review and bioinformatic analysis. Cells. 2018;7(12):249. https://doi.org/10.3390/cells7120249.CrossRefPubMedCentral

18.

Wang Y, Russell I, Chen C. MicroRNA and stem cell regulation. CurrOpin Mol Ther. 2009;11:292–8.

19.

Thum T, Condorelli G. Long noncoding RNAs and microRNAs in cardiovascular pathophysiology. Circ Res. 2015;116(4):751–62. https://doi.org/10.1161/CIRCRESAHA.116.303549.CrossRefPubMed

20.

Weber JA, Baxter DH, Zhang S, Huang DY, Huang KH, Lee MJ, Galas DJ, Wang K. The microRNA spectrum in 12 body fluids. Clin Chem. 2010;56(11):1733–41. https://doi.org/10.1373/clinchem.2010.147405.CrossRefPubMedPubMedCentral

21.

Choi JL, Li S, Han JY. Platelet function tests: a review of progresses in clinical application. Biomed Res Int. 2014;2014:456569. https://doi.org/10.1155/2014/456569.CrossRefPubMedPubMedCentral

22.

Streit S, Michalski CW, Erkan M, Kleeff J, Friess H. Northern blot analysis for detection and quantification of RNA in pancreatic cancer cells and tissues. Nat Protoc. 2009;4(1):37–43. https://doi.org/10.1038/nprot.2008.216.CrossRefPubMed

23.

Várallyay E, Burgyán J, Havelda Z. MicroRNA detection by northern blotting using locked nucleic acid probes. Nat Protoc. 2008;3(2):190–6. https://doi.org/10.1038/nprot.2007.528.CrossRefPubMed

24.

Pordzik J, Pisarz K, De Rosa S, Jones AD, Eyileten C, Indolfi C, Malek L, Postula M. The potential role of platelet-related microRNAs in the development of cardiovascular events in high-risk populations, including diabetic patients: a review. Front Endocrinol. 2018;20(9):74. https://doi.org/10.3389/fendo.2018.00074.CrossRef

25.

Ferraro D, Champ J, Teste B, Serra M, Malaquin L, Viovy JL, de Cremoux P, Descroix S. Microfluidic platform combining droplets and magnetic tweezers: application to HER2 expression in cancer diagnosis. Sci Rep. 2016;9(6):25540. https://doi.org/10.1038/srep25540.CrossRef

26.

Eminaga S, Christodoulou DC, Vigneault F, Church GM, Seidman JG. Quantification of microRNA expression with next-generation sequencing. Curr Protoc Mol Biol. 2013;4(4):17. https://doi.org/10.1002/0471142727.mb0417s103.CrossRefPubMed

27.

Chugh P, Dittmer DP. Potential pitfalls in microRNA profiling. Wiley Interdiscip Rev RNA. 2012;3(5):601–16. https://doi.org/10.1002/wrna.1120.CrossRefPubMedPubMedCentral

28.

De Rosa S, Indolfi C. Circulating microRNAs as biomarkers in cardiovascular diseases. Exp Suppl. 2015;106:139–49. https://doi.org/10.1007/978-3-0348-0955-9_6.CrossRefPubMed

29.

Kong L, Zhu J, Han W, Jiang X, Xu M, Zhao Y, Dong Q, Pang Z, Guan Q, Gao L, Zhao J, Zhao L. Significance of serum microRNAs in pre-diabetes and newly diagnosed type 2 diabetes: a clinical study. Acta Diabetol. 2011;48(1):61–9. https://doi.org/10.1007/s00592-010-0226-0.CrossRefPubMed

30.

Karolina DS, Tavintharan S, Armugam A, Sepramaniam S, Pek SL, Wong MT, Lim SC, Sum CF, Jeyaseelan K. Circulating miRNA profiles in patients with metabolic syndrome. J Clin Endocrinol Metab. 2012;97(12):E2271–6. https://doi.org/10.1210/jc.2012-1996.CrossRefPubMed

31.

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 Res Int. 2013;2013:761617. https://doi.org/10.1155/2013/761617.CrossRefPubMedPubMedCentral

32.

Liu Y, Gao G, Yang C, Zhou K, Shen B, Liang H, Jiang X. The role of circulating microRNA-126 (miR-126): a novel biomarker for screening prediabetes and newly diagnosed type 2 diabetes mellitus. Int J Mol Sci. 2014;15(6):10567–77. https://doi.org/10.3390/ijms150610567.CrossRefPubMedPubMedCentral

33.

Ghorbani S, Mahdavi R, Alipoor B, Panahi G, Nasli Esfahani E, Razi F, Taghikhani M, Meshkani R. Decreased serum microRNA-21 level is associated with obesity in healthy and type 2 diabetic subjects. Arch Physiol Biochem. 2018;124(4):300–5. https://doi.org/10.1080/13813455.2017.1396349.CrossRefPubMed

34.

Al-Muhtaresh HA, Al-Kafaji G. Evaluation of two-diabetes related microRNAs suitability as earlier blood biomarkers for detecting prediabetes and type 2 diabetes mellitus. J Clin Med. 2018;7(2):12. https://doi.org/10.3390/jcm7020012.CrossRefPubMedCentral

35.

Jiménez-Lucena R, Rangel-Zúñiga OA, Alcalá-Díaz JF, López-Moreno J, Roncero-Ramos I, Molina-Abril H, Yubero-Serrano EM, Caballero-Villarraso J, Delgado-Lista J, Castaño JP, Ordovás JM, Pérez-Martinez P, Camargo A, López-Miranda J. Circulating miRNAs as predictive biomarkers of type 2 diabetes mellitus development in coronary heart disease patients from the CORDIOPREV study. Mol Ther Nucleic Acids. 2018;7(12):146–57. https://doi.org/10.1016/j.omtn.2018.05.002.CrossRef

36.

Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, Mayr A, Weger S, Oberhollenzer F, Bonora E, Shah A, Willeit J, Mayr M. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010;107(6):810–7. https://doi.org/10.1161/CIRCRESAHA.110.226357.CrossRefPubMed

37.

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):60–3. https://doi.org/10.1016/j.bbrc.2015.05.017.CrossRefPubMed

38.

Lontchi-Yimagou E, Sobngwi E, Matsha TE, Kengne AP. Diabetes mellitus and inflammation. Curr Diab Rep. 2013;13(3):435–44. https://doi.org/10.1007/s11892-013-0375-y.CrossRefPubMed

39.

Kapłon-Cieślicka A, Postuła M, Rosiak M, Peller M, Kondracka A, Serafin A, Trzepla E, Opolski G, Filipiak KJ. Association of adipokines and inflammatory markers with lipid control in type 2 diabetes. Pol Arch Med Wewn. 2015;125(6):414–23.PubMed

40.

Postula M, Janicki PK, Eyileten C, Rosiak M, Kaplon-Cieslicka A, Sugino S, Wilimski R, Kosior DA, Opolski G, Filipiak KJ, Mirowska-Guzel D. Next-generation re-sequencing of genes involved in increased platelet reactivity in diabetic patients on acetylsalicylic acid. Platelets. 2016;27(4):357–64. https://doi.org/10.3109/09537104.2015.1109071.CrossRefPubMed

41.

Rivas Rios JR, Franchi F, Rollini F, Angiolillo DJ. Diabetes and antiplatelet therapy: from bench to bedside. Cardiovasc Diagn Ther. 2018;8(5):594–609. https://doi.org/10.21037/cdt.2018.05.09.CrossRefPubMedPubMedCentral

42.

Calverley DC, Baldermann LV, Moran K, Chen NN, McFann K. Platelet FcgammaRIIA expression is associated with the alpha2 integrin C807T gene polymorphism in type 2 diabetes. Platelets. 2006;17(2):78–83. https://doi.org/10.1080/09537100500260865.CrossRefPubMed

43.

Calverley DC, Brass E, Hacker MR, Tsao-Wei DD, Espina BM, Pullarkat VA, Hodis HN, Groshen S. Potential role of platelet FcgammaRIIA in collagen-mediated platelet activation associated with atherothrombosis. Atherosclerosis. 2002;164(2):261–7.CrossRefPubMed

44.

Balasubramanyam M, Aravind S, Gokulakrishnan K, Prabu P, Sathishkumar C, Ranjani H, Mohan V. Impaired miR-146a expression links subclinical inflammation and insulin resistance in type 2 diabetes. Mol Cell Biochem. 2011;351(1–2):197–205. https://doi.org/10.1007/s11010-011-0727-3.CrossRefPubMed

45.

Luo M, Li R, Deng X, Ren M, Chen N, Zeng M, Yan K, Xia J, Liu F, Ma W, Yang Y, Wan Q, Wu J. Platelet-derived miR-103b as a novel biomarker for the early diagnosis of type 2 diabetes. Acta Diabetol. 2015;52(5):943–9. https://doi.org/10.1007/s00592-015-0733-0.CrossRefPubMed

46.

Mahdi T, Hänzelmann S, Salehi A, Muhammed SJ, Reinbothe TM, Tang Y, Axelsson AS, Zhou Y, Jing X, Almgren P, Krus U, Taneera J, Blom AM, Lyssenko V, Esguerra JL, Hansson O, Eliasson L, Derry J, Zhang E, Wollheim CB, Groop L, Renström E, Rosengren AH. Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes. Cell Metab. 2012;16(5):625–33. https://doi.org/10.1016/j.cmet.2012.10.009.CrossRefPubMed

47.

Olivieri F, Spazzafumo L, Bonafè M, Recchioni R, Prattichizzo F, Marcheselli F, Micolucci L, Mensà E, Giuliani A, Santini G, Gobbi M, Lazzarini R, Boemi M, Testa R, Antonicelli R, Procopio AD, Bonfigli AR. MiR-21-5p and miR-126a-3p levels in plasma and circulating angiogenic cells: relationship with type 2 diabetes complications. Oncotarget. 2015;6(34):35372–82. https://doi.org/10.18632/oncotarget.6164.CrossRefPubMedPubMedCentral

48.

Giannella A, Radu CM, Franco L, Campello E, Simioni P, Avogaro A, de Kreutzenberg SV, Ceolotto G. Circulating levels and characterization of microparticles in patients with different degrees of glucose tolerance. Cardiovasc Diabetol. 2017;16(1):118. https://doi.org/10.1186/s12933-017-0600-0.CrossRefPubMedPubMedCentral

49.

Witkowski M, Weithauser A, Tabaraie T, Steffens D, Kränkel N, Witkowski M, Stratmann B, Tschoepe D, Landmesser U, Rauch-Kroehnert U. Micro-RNA-126 reduces the blood thrombogenicity in diabetes mellitus via targeting of tissue factor. Arterioscler Thromb Vasc Biol. 2016;36(6):1263–71. https://doi.org/10.1161/ATVBAHA.115.306094.CrossRefPubMedPubMedCentral

50.

Harris TA, Yamakuchi M, Kondo M, Oettgen P, Lowenstein CJ. Ets-1 and Ets-2 regulate the expression of microRNA-126 in endothelial cells. Arterioscler Thromb Vasc Biol. 2010;30(10):1990–7. https://doi.org/10.1161/ATVBAHA.110.211706.CrossRefPubMedPubMedCentral

51.

Dhananjayan R, Koundinya KS, Malati T, Kutala VK. Endothelial dysfunction in type 2 diabetes mellitus. Indian J Clin Biochem. 2016;31(4):372–9. https://doi.org/10.1007/s12291-015-0516-y.CrossRefPubMed

52.

Kaur R, Kaur M, Singh J. Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies. Cardiovasc Diabetol. 2018;17(1):121. https://doi.org/10.1186/s12933-018-0763-3.CrossRefPubMedPubMedCentral

53.

Jagadapillai R, Rane MJ, Lin X, Roberts AM, Hoyle GW, Cai L, Gozal E. Diabetic microvascular disease and pulmonary fibrosis: the contribution of platelets and systemic inflammation. Int J Mol Sci. 2016;17(11):1853. https://doi.org/10.3390/ijms17111853.CrossRefPubMedCentral

54.

Jansen F, Wang H, Przybilla D, Franklin BS, Dolf A, Pfeifer P, Schmitz T, Flender A, Endl E, Nickenig G, Werner N. Vascular endothelial microparticles-incorporated microRNAs are altered in patients with diabetes mellitus. Cardiovasc Diabetol. 2016;22(15):49. https://doi.org/10.1186/s12933-016-0367-8.CrossRef

55.

Deng X, Liu Y, Luo M, Wu J, Ma R, Wan Q, Wu J. Circulating miRNA-24 and its target YKL-40 as potential biomarkers in patients with coronary heart disease and type 2 diabetes mellitus. Oncotarget. 2017;8(38):63038–46. https://doi.org/10.18632/oncotarget.18593.CrossRefPubMedPubMedCentral

56.

Amr KS, Abdelmawgoud H, Ali ZY, Shehata S, Raslan HM. Potential value of circulating microRNA-126 and microRNA-210 as biomarkers for type 2 diabetes with coronary artery disease. Br J Biomed Sci. 2018;75(2):82–7. https://doi.org/10.1080/09674845.2017.1402404.CrossRefPubMed

57.

Stępień EŁ, Durak-Kozica M, Kamińska A, Targosz-Korecka M, Libera M, Tylko G, Opalińska A, Kapusta M, Solnica B, Georgescu A, Costa MC, Czyżewska-Buczyńska A, Witkiewicz W, Małecki MT, Enguita FJ. Circulating ectosomes: determination of angiogenic microRNAs in type 2 diabetes. Theranostics. 2018;8(14):3874–90. https://doi.org/10.7150/thno.23334.CrossRefPubMedPubMedCentral

58.

Rollini F, Franchi F, Muñiz-Lozano A, Angiolillo DJ. Platelet function profiles in patients with diabetes mellitus. J Cardiovasc Transl Res. 2013;6(3):329–45. https://doi.org/10.1007/s12265-013-9449-0.CrossRefPubMed

59.

Stratz C, Nührenberg T, Fiebich BL, Amann M, Kumar A, Binder H, Hoffmann I, Valina C, Hochholzer W, Trenk D, Neumann FJ. Controlled type II diabetes mellitus has no major influence on platelet micro-RNA expression. Results from micro-array profiling in a cohort of 60 patients. Thromb Haemost. 2014;111(5):902–11. https://doi.org/10.1160/th13-06-0476.CrossRefPubMed

60.

Fejes Z, Póliska S, Czimmerer Z, Káplár M, Penyige A, Gál Szabó G, Beke Debreceni I, Kunapuli SP, Kappelmayer J, Nagy B Jr. Hyperglycaemia suppresses microRNA expression in platelets to increase P2RY12 and SELP levels in type 2 diabetes mellitus. Thromb Haemost. 2017;117(3):529–42. https://doi.org/10.1160/TH16-04-0322.CrossRefPubMed

61.

Zampetaki A, Willeit P, Tilling L, Drozdov I, Prokopi M, Renard JM, Mayr A, Weger S, Schett G, Shah A, Boulanger CM, Willeit J, Chowienczyk PJ, Kiechl S, Mayr M. Prospective study on circulating MicroRNAs and risk of myocardial infarction. J Am Coll Cardiol. 2012;60(4):290–9. https://doi.org/10.1016/j.jacc.2012.03.056.CrossRefPubMed

62.

Witkowski M, Tabaraie T, Steffens D, Friebel J, Dörner A, Skurk C, Witkowski M, Stratmann B, Tschoepe D, Landmesser U, Rauch U. MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes. Cardiovasc Diabetol. 2018;17(1):34. https://doi.org/10.1186/s12933-018-0678-z.CrossRefPubMedPubMedCentral

63.

Fichtlscherer S, De Rosa S, Fox H, Schwietz T, Fischer A, Liebetrau C, Weber M, Hamm CW, Röxe T, Müller-Ardogan M, Bonauer A, Zeiher AM, Dimmeler S. Circulating microRNAs in patients with coronary artery disease. Circ Res. 2010;107(5):677–84. https://doi.org/10.1161/CIRCRESAHA.109.215566.CrossRefPubMed

64.

Zhuang G, Wu X, Jiang Z, Kasman I, Yao J, Guan Y, et al. Tumour-secreted mir-9 promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway. EMBO J. 2012;31(17):3513–23. https://doi.org/10.1038/emboj.2012.183.CrossRefPubMedPubMedCentral

65.

Nicoli S, Standley C, Walker P, Hurlstone A, Fogarty KE, Lawson ND. MicroRNA-mediated integration of haemodynamics and Vegf signalling during angiogenesis. Nature. 2010;464(7292):1196–200. https://doi.org/10.1038/nature08889.CrossRefPubMedPubMedCentral

66.

Hergenreider E, Heydt S, Tréguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, Braun T, Urbich C, Boon RA, Dimmeler S. Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol. 2012;14(3):249–56. https://doi.org/10.1038/ncb2441.CrossRefPubMed

67.

Vasa-Nicotera M, Chen H, Tucci P, Yang AL, Saintigny G, Menghini R, Mahè C, Agostini M, Knight RA, Melino G, Federici M. miR-146a is modulated in human endothelial cell with aging. Atherosclerosis. 2011;217(2):326–30. https://doi.org/10.1016/j.atherosclerosis.2011.03.034.CrossRefPubMed

68.

Cheng HS, Sivachandran N, Lau A, Boudreau E, Zhao JL, Baltimore D, Delgado-Olguin P, Cybulsky MI, Fish JE. MicroRNA-146 represses endothelial activation by inhibiting pro-inflammatory pathways. EMBO Mol Med. 2013;5(7):1017–34. https://doi.org/10.1002/emmm.201202318.CrossRefPubMed

69.

De Rosa S, Fichtlscherer S, Lehmann R, Assmus B, Dimmeler S, Zeiher AM. Transcoronary concentration gradients of circulating microRNAs. Circulation. 2011;124(18):1936–44. https://doi.org/10.1161/CIRCULATIONAHA.111.037572.CrossRefPubMed

70.

De Rosa S, Eposito F, Carella C, Strangio A, Ammirati G, Sabatino J, Abbate FG, Iaconetti C, Liguori V, Pergola V, Polimeni A, Coletta S, Gareri C, Trimarco B, Stabile G, Curcio A, Indolfi C, Rapacciuolo A. Transcoronary concentration gradients of circulating microRNAs in heart failure. Eur J Heart Fail. 2018;20(6):1000–10. https://doi.org/10.1002/ejhf.1119.CrossRefPubMed

71.

Carino A, De Rosa S, Sorrentino S, Polimeni A, Sabatino J, Caiazzo G, Torella D, Spaccarotella C, Mongiardo A, Strangio A, Filippis C, Indolfi C. Modulation of circulating MicroRNAs levels during the switch from clopidogrel to ticagrelor. Biomed Res Int. 2016;2016:3968206. https://doi.org/10.1155/2016/3968206.CrossRefPubMedPubMedCentral

72.

Ru Y, Kechris KJ, Tabakoff B, Hoffman P, Radcliffe RA, Bowler R, Mahaffey S, Rossi S, Calin GA, Bemis L, Theodorescu D. The multiMiR R package and database: integration of microRNA–target interactions along with their disease and drug associations. Nucleic Acids Res. 2014;42(17):e133. https://doi.org/10.1093/nar/gku631.CrossRefPubMedPubMedCentral

73.

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–504. https://doi.org/10.1101/gr.1239303.CrossRefPubMedPubMedCentral

74.

Durinck S, Spellman PT, Birney E, Huber W. Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat Protoc. 2009;4(8):1184–91. https://doi.org/10.1038/nprot.2009.97.CrossRefPubMedPubMedCentral

75.

Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K. KEGG: new perspectives on genomes, pathways, diseases and drugs. Nucleic Acids Res. 2017;45(D1):D353–61. https://doi.org/10.1093/nar/gkw1092.CrossRefPubMed

76.

Fabregat A, Jupe S, Matthews L, Sidiropoulos K, Gillespie M, Garapati P, Haw R, Jassal B, Korninger F, May B, Milacic M, Roca CD, Rothfels K, Sevilla C, Shamovsky V, Shorser S, Varusai T, Viteri G, Weiser J, Wu G, Stein L, Hermjakob H, D’Eustachio P. The reactome pathway knowledgebase. Nucleic Acids Res. 2018;46(D1):D649–55. https://doi.org/10.1093/nar/gkx1132.CrossRefPubMed

77.

Doncheva NT, Morris J, Gorodkin J, Jensen LJ. Cytoscape stringApp: network analysis and visualization of proteomics data. J Proteome Res. 2018. https://doi.org/10.1021/acs.jproteome.8b00702.CrossRefPubMedPubMedCentral

78.

Nielsen LB, Wang C, Sørensen K, Bang-Berthelsen CH, Hansen L, Andersen ML, Hougaard P, Juul A, Zhang CY, Pociot F, Mortensen HB. Circulating levels of microRNA from children with newly diagnosed type 1 diabetes and healthy controls: evidence that miR-25 associates to residual beta-cell function and glycaemic control during disease progression. Exp Diabetes Res. 2012;2012:896362. https://doi.org/10.1155/2012/896362.CrossRefPubMedPubMedCentral

79.

Kim JW, You YH, Jung S, Suh-Kim H, Lee IK, Cho JH, Yoon KH. miRNA-30a-5p-mediated silencing of Beta2/NeuroD expression is an important initial event of glucotoxicity-induced beta cell dysfunction in rodent models. Diabetologia. 2013;56(4):847–55. https://doi.org/10.1007/s00125-012-2812-x.CrossRefPubMed

80.

Delić D, Eisele C, Schmid R, Baum P, Wiech F, Gerl M, Zimdahl H, Pullen SS, Urquhart R. Urinary exosomal miRNA signature in type ii diabetic nephropathy patients. PLoS ONE. 2016;11(3):e0150154. https://doi.org/10.1371/journal.pone.0150154.CrossRefPubMedPubMedCentral

81.

Jiang J, Liang G, Wu Z, Mo H, You W, Wang Z, Wu K, Guo R. Naringenin alleviates high d-glucose-induced injuries through up-regulation of microRNA-30d-5p level in human AC16 cardiac cells. J Appl Biomed. 2018;16:274–80. https://doi.org/10.1016/j.jab.2018.02.005.CrossRef

82.

Seyhan AA, Nunez Lopez YO, Xie H, Yi F, Mathews C, Pasarica M, Pratley RE. Pancreas-enriched miRNAs are altered in the circulation of subjects with diabetes: a pilot cross-sectional study. Sci Rep. 2016;25(6):31479. https://doi.org/10.1038/srep31479.CrossRef

83.

Caserta S, Mengozzi M, Kern F, Newbury SF, Ghezzi P, Llewelyn MJ. Severity of systemic inflammatory response syndrome affects the blood levels of circulating inflammatory-relevant MicroRNAs. Front Immunol. 2018;5(8):1977. https://doi.org/10.3389/fimmu.2017.01977.CrossRef

84.

Caserta S, Kern F, Cohen J, Drage S, Newbury SF, Llewelyn MJ. Circulating plasma microRNAs can differentiate human sepsis and systemic inflammatory response syndrome (SIRS). Sci Rep. 2016;6:28006. https://doi.org/10.1038/srep28006.CrossRefPubMedPubMedCentral

85.

Tryggestad JB, Vishwanath A, Jiang S, Mallappa A, Teague AM, Takahashi Y, Thompson DM, Chernausek SD. Influence of gestational diabetes mellitus on human umbilical vein endothelial cell miRNA. Clin Sci. 2016;130(21):1955–67. https://doi.org/10.1042/CS20160305.CrossRef

86.

Genetics Home Reference. https://ghr.nlm.nih.gov/gene/PRKAR1A. Accessed 3 Mar 2019.

87.

Hussain MA, Stratakis C, Kirschner L. Prkar1a in the regulation of insulin secretion. Horm Metab Res. 2012;44(10):759–65. https://doi.org/10.1055/s-0032-1321866.CrossRefPubMedPubMedCentral

88.

Santilli F, Simeone P, Liani R, Davì G. Platelets and diabetes mellitus. Prostaglandins Other Lipid Mediat. 2015;120:28–39. https://doi.org/10.1016/j.prostaglandins.2015.05.002.CrossRefPubMed

Title: Significance of circulating microRNAs in diabetes mellitus type 2 and platelet reactivity: bioinformatic analysis and review
Authors: Justyna Pordzik
Daniel Jakubik
Joanna Jarosz-Popek
Zofia Wicik
Ceren Eyileten
Salvatore De Rosa
Ciro Indolfi
Jolanta M. Siller-Matula
Pamela Czajka
Marek Postula
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Insulins
Type 2 Diabetes
Insulins
Biomarkers
Published in: Cardiovascular Diabetology / Issue 1/2019
Electronic ISSN: 1475-2840
DOI: https://doi.org/10.1186/s12933-019-0918-x

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Significance of circulating microRNAs in diabetes mellitus type 2 and platelet reactivity: bioinformatic analysis and review

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2019

Comparative outcomes of heart failure among existent classes of anti-diabetic agents: a network meta-analysis of 171,253 participants from 91 randomized controlled trials

Metformin use and cardiovascular outcomes after acute myocardial infarction in patients with type 2 diabetes: a cohort study

Cardiac ischemia–reperfusion injury under insulin-resistant conditions: SGLT1 but not SGLT2 plays a compensatory protective role in diet-induced obesity

Machine-learning to stratify diabetic patients using novel cardiac biomarkers and integrative genomics

Effect of pioglitazone in acute ischemic stroke patients with diabetes mellitus: a nested case–control study

Risk of early mortality and cardiovascular disease in type 1 diabetes: a comparison with type 2 diabetes, a nationwide study

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page