MicroRNAs as Regulators and Biomarkers of Platelet Function and Activity in Coronary Artery Disease

Stefan Stojkovic; Anne Yaël Nossent; Paul Haller; Bernhard Jäger; Kris G. Vargas; Johann Wojta; Kurt Huber

doi:10.1055/s-0039-1693702

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2019; 119(10): 1563-1572
DOI: 10.1055/s-0039-1693702

Theme Issue Article

Georg Thieme Verlag KG Stuttgart · New York

MicroRNAs as Regulators and Biomarkers of Platelet Function and Activity in Coronary Artery Disease

Authors

Stefan Stojkovic

¹University Clinic for Internal Medicine II, Department of Cardiology, Medical University of Vienna, Vienna, Austria
Anne Yaël Nossent

¹University Clinic for Internal Medicine II, Department of Cardiology, Medical University of Vienna, Vienna, Austria
Paul Haller

²3rd Department of Internal Medicine, Cardiology, Intensive Care Medicine and Chest Pain Unit, Wilhelminenhospital, Vienna, Austria
Bernhard Jäger

²3rd Department of Internal Medicine, Cardiology, Intensive Care Medicine and Chest Pain Unit, Wilhelminenhospital, Vienna, Austria

³Medical Faculty, Sigmund Freud University, Vienna, Austria
Kris G. Vargas

²3rd Department of Internal Medicine, Cardiology, Intensive Care Medicine and Chest Pain Unit, Wilhelminenhospital, Vienna, Austria
Johann Wojta

¹University Clinic for Internal Medicine II, Department of Cardiology, Medical University of Vienna, Vienna, Austria

⁴Core Facilities, Medical University of Vienna, Vienna, Austria

⁵Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna Austria
Kurt Huber

²3rd Department of Internal Medicine, Cardiology, Intensive Care Medicine and Chest Pain Unit, Wilhelminenhospital, Vienna, Austria

³Medical Faculty, Sigmund Freud University, Vienna, Austria

Abstract

Microribonucleic acids (miRs) are small, noncoding ribonucleic acids (RNAs), which play an important role in the regulation of platelet function and activity. Several studies proposed a mechanistic role of platelet-related miRs in the pathophysiology of coronary artery disease (CAD) and atherothrombosis. Circulating, platelet-related miRs have been proposed as diagnostic, prognostic, as well as treatment response biomarkers in CAD and acute coronary syndrome (ACS). In this review, we summarize recent studies on the role of platelet-related miRs in the regulation of platelet function and activity. Furthermore, we review the studies investigating the role of platelet-related miRs as biomarkers in patients with CAD and ACS.

Keywords

microRNA - platelet function - coronary artery disease - acute myocardial infarction - acute coronary syndrome

Volltext

Referenzen

References
1 Baek D, Villén J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature 2008; 455 (7209): 64-71
2 Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell 2009; 136 (02) 215-233
3 Mitchell PS, Parkin RK, Kroh EM. , et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 2008; 105 (30) 10513-10518
4 Valadi H, Ekström K, Bossios A, Sjöstrand M, Lee JJ, Lötvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 2007; 9 (06) 654-659
5 Hunter MP, Ismail N, Zhang X. , et al. Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 2008; 3 (11) e3694
6 Vickers KC, Palmisano BT, Shoucri BM, Shamburek RD, Remaley AT. MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 2011; 13 (04) 423-433
7 Turchinovich A, Weiz L, Langheinz A, Burwinkel B. Characterization of extracellular circulating microRNA. Nucleic Acids Res 2011; 39 (16) 7223-7233
8 Wang GK, Zhu JQ, Zhang JT. , et al. Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 2010; 31 (06) 659-666
9 D'Alessandra Y, Devanna P, Limana F. , et al. Circulating microRNAs are new and sensitive biomarkers of myocardial infarction. Eur Heart J 2010; 31 (22) 2765-2773
10 Fichtlscherer S, De Rosa S, Fox H. , et al. Circulating microRNAs in patients with coronary artery disease. Circ Res 2010; 107 (05) 677-684
11 Tijsen AJ, Creemers EE, Moerland PD. , et al. MiR423-5p as a circulating biomarker for heart failure. Circ Res 2010; 106 (06) 1035-1039
12 Zampetaki A, Kiechl S, Drozdov I. , et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res 2010; 107 (06) 810-817
13 Stojkovic S, Jurisic M, Kopp CW. , et al. Circulating microRNAs identify patients at increased risk of in-stent restenosis after peripheral angioplasty with stent implantation. Atherosclerosis 2018; 269: 197-203
14 Ahlin F, Arfvidsson J, Vargas KG, Stojkovic S, Huber K, Wojta J. MicroRNAs as circulating biomarkers in acute coronary syndromes: a review. Vascul Pharmacol 2016; 81: 15-21
15 Hohensinner PJ, Kaun C, Ebenbauer B. , et al. Reduction of premature aging markers after gastric bypass surgery in morbidly obese patients. Obes Surg 2018; 28 (09) 2804-2810
16 Merkerova M, Belickova M, Bruchova H. Differential expression of microRNAs in hematopoietic cell lineages. Eur J Haematol 2008; 81 (04) 304-310
17 Landry P, Plante I, Ouellet DL, Perron MP, Rousseau G, Provost P. Existence of a microRNA pathway in anucleate platelets. Nat Struct Mol Biol 2009; 16 (09) 961-966
18 Rowley JW, Chappaz S, Corduan A. , et al. Dicer1-mediated miRNA processing shapes the mRNA profile and function of murine platelets. Blood 2016; 127 (14) 1743-1751
19 Nagalla S, Shaw C, Kong X. , et al. Platelet microRNA-mRNA coexpression profiles correlate with platelet reactivity. Blood 2011; 117 (19) 5189-5197
20 Osman A, Fälker K. Characterization of human platelet microRNA by quantitative PCR coupled with an annotation network for predicted target genes. Platelets 2011; 22 (06) 433-441
21 Stratz C, Nührenberg TG, Binder H. , et al. Micro-array profiling exhibits remarkable intra-individual stability of human platelet micro-RNA. Thromb Haemost 2012; 107 (04) 634-641
22 Plé H, Landry P, Benham A, Coarfa C, Gunaratne PH, Provost P. The repertoire and features of human platelet microRNAs. PLoS One 2012; 7 (12) e50746
23 Simon LM, Edelstein LC, Nagalla S. , et al. Human platelet microRNA-mRNA networks associated with age and gender revealed by integrated plateletomics. Blood 2014; 123 (16) e37-e45
24 Edelstein LC, Simon LM, Montoya RT. , et al. Racial differences in human platelet PAR4 reactivity reflect expression of PCTP and miR-376c. Nat Med 2013; 19 (12) 1609-1616
25 Nassa G, Giurato G, Cimmino G. , et al. Splicing of platelet resident pre-mRNAs upon activation by physiological stimuli results in functionally relevant proteome modifications. Sci Rep 2018; 8 (01) 498
26 Elgheznawy A, Shi L, Hu J. , et al. Dicer cleavage by calpain determines platelet microRNA levels and function in diabetes. Circ Res 2015; 117 (02) 157-165
27 Leierseder S, Petzold T, Zhang L, Loyer X, Massberg S, Engelhardt S. MiR-223 is dispensable for platelet production and function in mice. Thromb Haemost 2013; 110 (06) 1207-1214
28 Welten SM, Goossens EA, Quax PH, Nossent AY. The multifactorial nature of microRNAs in vascular remodelling. Cardiovasc Res 2016; 110 (01) 6-22
29 Luo M, Li R, Ren M. , et al. Hyperglycaemia-induced reciprocal changes in miR-30c and PAI-1 expression in platelets. Sci Rep 2016; 6: 36687
30 Fejes Z, Póliska S, Czimmerer Z. , et al. Hyperglycaemia suppresses microRNA expression in platelets to increase P2RY12 and SELP levels in type 2 diabetes mellitus. Thromb Haemost 2017; 117 (03) 529-542
31 Garcia A, Dunoyer-Geindre S, Zapilko V, Nolli S, Reny JL, Fontana P. Functional validation of microRNA-126-3p as a platelet reactivity regulator using human haematopoietic stem cells. Thromb Haemost 2019; 119 (02) 254-263
32 Kaudewitz D, Skroblin P, Bender LH. , et al. Association of microRNAs and YRNAs with platelet function. Circ Res 2016; 118 (03) 420-432
33 Kondkar AA, Bray MS, Leal SM. , et al. VAMP8/endobrevin is overexpressed in hyperreactive human platelets: suggested role for platelet microRNA. J Thromb Haemost 2010; 8 (02) 369-378
34 Zhou Y, Abraham S, Andre P. , et al. Anti-miR-148a regulates platelet FcγRIIA signaling and decreases thrombosis in vivo in mice. Blood 2015; 126 (26) 2871-2881
35 Miao X, Rahman MF, Jiang L. , et al. Thrombin-reduced miR-27b attenuates platelet angiogenic activities in vitro via enhancing platelet synthesis of anti-angiogenic thrombospondin-1. J Thromb Haemost 2018; 16 (04) 791-801
36 Thum T, Gross C, Fiedler J. , et al. MicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts. Nature 2008; 456 (7224): 980-984
37 Barwari T, Eminaga S, Mayr U. , et al. Inhibition of profibrotic microRNA-21 affects platelets and their releasate. JCI Insight 2018; 3 (21) 3
38 Ambrose AR, Alsahli MA, Kurmani SA, Goodall AH. Comparison of the release of microRNAs and extracellular vesicles from platelets in response to different agonists. Platelets 2018; 29 (05) 446-454
39 Gidlöf O, van der Brug M, Ohman J. , et al. Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression. Blood 2013; 121 (19) 3908-3917
40 Laffont B, Corduan A, Plé H. , et al. Activated platelets can deliver mRNA regulatory Ago2•microRNA complexes to endothelial cells via microparticles. Blood 2013; 122 (02) 253-261
41 Pan Y, Liang H, Liu H. , et al. Platelet-secreted microRNA-223 promotes endothelial cell apoptosis induced by advanced glycation end products via targeting the insulin-like growth factor 1 receptor. J Immunol 2014; 192 (01) 437-446
42 Li J, Tan M, Xiang Q, Zhou Z, Yan H. Thrombin-activated platelet-derived exosomes regulate endothelial cell expression of ICAM-1 via microRNA-223 during the thrombosis-inflammation response. Thromb Res 2017; 154: 96-105
43 Zhang Y, Zhang W, Zha C, Liu Y. Platelets activated by the anti-β2GPI/β2GPI complex release microRNAs to inhibit migration and tube formation of human umbilical vein endothelial cells. Cell Mol Biol Lett 2018; 23: 24
44 Tan M, Yan HB, Li JN. , et al. Thrombin stimulated platelet-derived exosomes inhibit platelet-derived growth factor receptor-beta expression in vascular smooth muscle cells. Cell Physiol Biochem 2016; 38 (06) 2348-2365
45 Yang Y, Luo H, Liu S. , et al. Platelet microparticles-containing miR-4306 inhibits human monocyte-derived macrophages migration through VEGFA/ERK1/2/NF-κB signaling pathways. Clin Exp Hypertens 2019; 41 (05) 481-491
46 Risitano A, Beaulieu LM, Vitseva O, Freedman JE. Platelets and platelet-like particles mediate intercellular RNA transfer. Blood 2012; 119 (26) 6288-6295
47 Flierl U, Nero TL, Lim B. , et al. Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators. J Exp Med 2015; 212 (02) 129-137
48 Sondermeijer BM, Bakker A, Halliani A. , et al. Platelets in patients with premature coronary artery disease exhibit upregulation of miRNA340* and miRNA624*. PLoS One 2011; 6 (10) e25946
49 Willeit P, Zampetaki A, Dudek K. , et al. Circulating microRNAs as novel biomarkers for platelet activation. Circ Res 2013; 112 (04) 595-600
50 de Boer HC, van Solingen C, Prins J. , et al. Aspirin treatment hampers the use of plasma microRNA-126 as a biomarker for the progression of vascular disease. Eur Heart J 2013; 34 (44) 3451-3457
51 Shi R, Ge L, Zhou X. , et al. Decreased platelet miR-223 expression is associated with high on-clopidogrel platelet reactivity. Thromb Res 2013; 131 (06) 508-513
52 Zhang YY, Zhou X, Ji WJ. , et al. Decreased circulating microRNA-223 level predicts high on-treatment platelet reactivity in patients with troponin-negative non-ST elevation acute coronary syndrome. J Thromb Thrombolysis 2014; 38 (01) 65-72
53 Chyrchel B, Totoń-Żurańska J, Kruszelnicka O. , et al. Association of plasma miR-223 and platelet reactivity in patients with coronary artery disease on dual antiplatelet therapy: a preliminary report. Platelets 2015; 26 (06) 593-597
54 Peng L, Liu J, Qin L. , et al. Interaction between platelet-derived microRNAs and CYP2C19*2 genotype on clopidogrel antiplatelet responsiveness in patients with ACS. Thromb Res 2017; 157: 97-102
55 Binderup HG, Houlind K, Madsen JS, Brasen CL. Aspirin resistance may be identified by miR-92a in plasma combined with platelet distribution width. Clin Biochem 2016; 49 (15) 1167-1172
56 Chen S, Qi X, Chen H. , et al. Expression of miRNA-26a in platelets is associated with clopidogrel resistance following coronary stenting. Exp Ther Med 2016; 12 (01) 518-524
57 Chen YC, Lin FY, Lin YW. , et al. Platelet microRNA 365-3p expression correlates with high on-treatment platelet reactivity in coronary artery disease patients. Cardiovasc Drugs Ther 2019; 33 (02) 129-137
58 Carino A, De Rosa S, Sorrentino S. , et al. Modulation of circulating microRNAs levels during the switch from clopidogrel to ticagrelor. BioMed Res Int 2016; 2016: 3968206
59 La Rosa G, Biasucci LM, Mandolini C. , et al. Platelet miRNA-26b down-regulates multidrug resistance protein 4 in patients on chronic aspirin treatment. J Cardiovasc Med (Hagerstown) 2018; 19 (10) 611-613
60 Massimi I, Lotti LV, Temperilli F. , et al. Enhanced platelet MRP4 expression and correlation with platelet function in patients under chronic aspirin treatment. Thromb Haemost 2016; 116 (06) 1100-1110
61 Sun X, Zhang M, Sanagawa A. , et al. Circulating microRNA-126 in patients with coronary artery disease: correlation with LDL cholesterol. Thromb J 2012; 10 (01) 16
62 Long G, Wang F, Duan Q. , et al. Human circulating microRNA-1 and microRNA-126 as potential novel indicators for acute myocardial infarction. Int J Biol Sci 2012; 8 (06) 811-818
63 Wang KJ, Zhao X, Liu YZ. , et al. Circulating MiR-19b-3p, MiR-134-5p and MiR-186-5p are promising novel biomarkers for early diagnosis of acute myocardial infarction. Cell Physiol Biochem 2016; 38 (03) 1015-1029
64 Zile MR, Mehurg SM, Arroyo JE, Stroud RE, DeSantis SM, Spinale FG. Relationship between the temporal profile of plasma microRNA and left ventricular remodeling in patients after myocardial infarction. Circ Cardiovasc Genet 2011; 4 (06) 614-619
65 Li C, Fang Z, Jiang T. , et al. Serum microRNAs profile from genome-wide serves as a fingerprint for diagnosis of acute myocardial infarction and angina pectoris. BMC Med Genomics 2013; 6: 16
66 Corsten MF, Dennert R, Jochems S. , et al. Circulating microRNA-208b and microRNA-499 reflect myocardial damage in cardiovascular disease. Circ Cardiovasc Genet 2010; 3 (06) 499-506
67 Coskunpinar E, Cakmak HA, Kalkan AK, Tiryakioglu NO, Erturk M, Ongen Z. Circulating miR-221-3p as a novel marker for early prediction of acute myocardial infarction. Gene 2016; 591 (01) 90-96
68 Oerlemans MI, Mosterd A, Dekker MS. , et al. Early assessment of acute coronary syndromes in the emergency department: the potential diagnostic value of circulating microRNAs. EMBO Mol Med 2012; 4 (11) 1176-1185
69 Darabi F, Aghaei M, Movahedian A, Pourmoghadas A, Sarrafzadegan N. The role of serum levels of microRNA-21 and matrix metalloproteinase-9 in patients with acute coronary syndrome. Mol Cell Biochem 2016; 422 (1-2): 51-60
70 Olivieri F, Antonicelli R, Lorenzi M. , et al. Diagnostic potential of circulating miR-499-5p in elderly patients with acute non ST-elevation myocardial infarction. Int J Cardiol 2013; 167 (02) 531-536
71 Wang F, Long G, Zhao C. , et al. Atherosclerosis-related circulating miRNAs as novel and sensitive predictors for acute myocardial infarction. PLoS One 2014; 9 (09) e105734
72 Ward JA, Esa N, Pidikiti R. , et al. Circulating cell and plasma microRNA profiles differ between non-ST-segment and ST-segment-elevation myocardial infarction. Fam Med Med Sci Res 2013; 2 (02) 108
73 Li S, Guo LZ, Kim MH, Han JY, Serebruany V. Platelet microRNA for predicting acute myocardial infarction. J Thromb Thrombolysis 2017; 44 (04) 556-564
74 Parahuleva MS, Euler G, Mardini A. , et al. Identification of microRNAs as potential cellular monocytic biomarkers in the early phase of myocardial infarction: a pilot study. Sci Rep 2017; 7 (01) 15974
75 Mukai N, Nakayama Y, Ishi S. , et al. Changes in microRNA expression level of circulating platelets contribute to platelet defect after cardiopulmonary bypass. Crit Care Med 2018; 46 (08) e761-e767
76 Mair J, Lindahl B, Hammarsten O. , et al. How is cardiac troponin released from injured myocardium?. Eur Heart J Acute Cardiovasc Care 2018; 7 (06) 553-560
77 Mair J, Lindahl B, Müller C. , et al. What to do when you question cardiac troponin values. Eur Heart J Acute Cardiovasc Care 2018; 7 (06) 577-586
78 Vafaie M, Slagman A, Möckel M. , et al. Prognostic value of undetectable hs Troponin T in suspected acute coronary syndrome. Am J Med 2016; 129 (03) 274-282
79 Devaux Y, Mueller M, Haaf P. , et al. Diagnostic and prognostic value of circulating microRNAs in patients with acute chest pain. J Intern Med 2015; 277 (02) 260-271
80 Zeller T, Keller T, Ojeda F. , et al. Assessment of microRNAs in patients with unstable angina pectoris. Eur Heart J 2014; 35 (31) 2106-2114
81 Karakas M, Schulte C, Appelbaum S. , et al. Circulating microRNAs strongly predict cardiovascular death in patients with coronary artery disease-results from the large AtheroGene study. Eur Heart J 2017; 38 (07) 516-523
82 Schulte C, Molz S, Appelbaum S. , et al. miRNA-197 and miRNA-223 predict cardiovascular death in a cohort of patients with symptomatic coronary artery disease. PLoS One 2015; 10 (12) e0145930
83 Yu XY, Chen JY, Zheng ZW. , et al. Plasma miR-126 as a potential marker predicting major adverse cardiac events in dual antiplatelet-treated patients after percutaneous coronary intervention. EuroIntervention 2013; 9 (05) 546-554
84 Jansen F, Yang X, Proebsting S. , et al. MicroRNA expression in circulating microvesicles predicts cardiovascular events in patients with coronary artery disease. J Am Heart Assoc 2014; 3 (06) e001249
85 Jakob P, Kacprowski T, Briand-Schumacher S. , et al. Profiling and validation of circulating microRNAs for cardiovascular events in patients presenting with ST-segment elevation myocardial infarction. Eur Heart J 2017; 38 (07) 511-515
86 Han M, Yang Z, Sayed D. , et al. GATA4 expression is primarily regulated via a miR-26b-dependent post-transcriptional mechanism during cardiac hypertrophy. Cardiovasc Res 2012; 93 (04) 645-654
87 Emmrich S, Henke K, Hegermann J, Ochs M, Reinhardt D, Klusmann JH. miRNAs can increase the efficiency of ex vivo platelet generation. Ann Hematol 2012; 91 (11) 1673-1684
88 Ren XP, Wu J, Wang X. , et al. MicroRNA-320 is involved in the regulation of cardiac ischemia/reperfusion injury by targeting heat-shock protein 20. Circulation 2009; 119 (17) 2357-2366
89 Zampetaki A, Willeit P, Tilling L. , et al. Prospective study on circulating MicroRNAs and risk of myocardial infarction. J Am Coll Cardiol 2012; 60 (04) 290-299
90 Badrnya S, Baumgartner R, Assinger A. Smoking alters circulating plasma microvesicle pattern and microRNA signatures. Thromb Haemost 2014; 112 (01) 128-136
91 Bye A, Røsjø H, Nauman J. , et al. Circulating microRNAs predict future fatal myocardial infarction in healthy individuals - The HUNT study. J Mol Cell Cardiol 2016; 97: 162-168
92 Häntzsch M, Tolios A, Beutner F. , et al. Comparison of whole blood RNA preservation tubes and novel generation RNA extraction kits for analysis of mRNA and MiRNA profiles. PLoS One 2014; 9 (12) e113298
93 Boeckel JN, Thomé CE, Leistner D, Zeiher AM, Fichtlscherer S, Dimmeler S. Heparin selectively affects the quantification of microRNAs in human blood samples. Clin Chem 2013; 59 (07) 1125-1127
94 Kaudewitz D, Lee R, Willeit P. , et al. Impact of intravenous heparin on quantification of circulating microRNAs in patients with coronary artery disease. Thromb Haemost 2013; 110 (03) 609-615
95 Zampetaki A, Mayr M. Analytical challenges and technical limitations in assessing circulating miRNAs. Thromb Haemost 2012; 108 (04) 592-598
96 Ach RA, Wang H, Curry B. Measuring microRNAs: comparisons of microarray and quantitative PCR measurements, and of different total RNA prep methods. BMC Biotechnol 2008; 8: 69
97 Gidlöf O, Andersson P, van der Pals J, Götberg M, Erlinge D. Cardiospecific microRNA plasma levels correlate with troponin and cardiac function in patients with ST elevation myocardial infarction, are selectively dependent on renal elimination, and can be detected in urine samples. Cardiology 2011; 118 (04) 217-226
98 Garzon R, Calin GA, Croce CM. MicroRNAs in cancer. Annu Rev Med 2009; 60: 167-179
99 Willeit P, Skroblin P, Moschen AR. , et al. Circulating microRNA-122 is associated with the risk of new-onset metabolic syndrome and type 2 diabetes. Diabetes 2017; 66 (02) 347-357
100 Li J, Chen H, Ren J. , et al. Effects of statin on circulating microRNAome and predicted function regulatory network in patients with unstable angina. BMC Med Genomics 2015; 8: 12
101 Weber M, Baker MB, Patel RS, Quyyumi AA, Bao G, Searles CD. MicroRNA expression profile in CAD patients and the impact of ACEI/ARB. Cardiol Res Pract 2011; 2011: 532915