Abstract
Platelets contain abundant microRNAs (miRs) that regulate gene expression and protein synthesis and may reflect platelet activation. We assessed platelet levels of miR-223, miR-126, and miR-22 in 82 patients with essential hypertension and 28 healthy individuals, using real-time reverse transcription polymerase chain reaction, and evaluated their relation with the patients’ clinical profile. Hypertensives had significantly lower platelet miR-22 and miR-223 levels (97.6 ± 170.3 in hypertensives versus 193.8 ± 228.9 in normotensives, p = 0.011, for miR-22; 91.3 ± 154.1 in hypertensives versus 189.9 ± 266.3 in normotensives, p = 0.022, for miR-223). Significant differences in platelet miR levels were also observed between hypertensives who had cardiovascular disease and those who did not (4.1 ± 3.6 versus 75.1 ± 85.2 for miR-126, 24.3 ± 62.9 versus 122.8 ± 187.9 for miR-22, and 10.1 ± 10.4 versus 119.3 ± 169.0 for miR-223, respectively; p < 0.001 for all). In addition, we found a significant negative correlation with systolic blood pressure (SBP) (r = −0.43, p < 0.001, for miR-22; r = −0.47, p < 0.001, for miR-223 in hypertensives; and r = −0.54, p < 0.001, for miR-126). Finally, receiver operating characteristic analysis showed that platelet miR levels were also strong prognostic markers for cardiovascular disease in these patients. In conclusion, platelet miR-22 and miR-223 levels are reduced according to the hypertension status and they are negatively correlated with SBP levels. Platelet miR levels are also related to the presence of overt cardiovascular disease in this population. Further studies are needed to elucidate the exact role of platelet miRs in platelet function and their utility as novel biomarkers of atherothrombotic risk in those patients.
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References
MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, et al. Blood pressure, stroke, and coronary heart disease. Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet. 1990;335:765–74.
Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Prospective Studies Collaboration Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903–13.
Poli KA, Tofler GH, Larson MG, Evans JC, Sutherland PA, Lipinska I, et al. Association of blood pressure with fibrinolytic potential in the Framingham offspring population. Circulation. 2000;101:264–9.
Spencer CG, Gurney D, Blann AD, Beevers DG, Lip GY. Anglo-Scandinavian Cardiac Outcomes Trial. Von Willebrand factor, soluble P-selectin, and target organ damage in hypertension: a substudy of the AngloScandinavian Cardiac Outcomes Trial (ASCOT). Hypertension. 2002;40:61–66. ASCOT Steering Committee.
Zampetaki A, Willeit P, Drozdov I, Kiechl S, Mayr M. Profiling of circulating microRNAs: from single biomarkers to re-wired networks. Cardiovasc Res. 2012;93:555–62.
Wang J, Chen J, Sen S. MicroRNA as biomarkers and diagnostics. J Cell Physiol. 2016;231:25–30.
Costa PM, Pedroso de Lima M. MicroRNAs as molecular targets for cancer therapy: on the modulation of microRNA expression. Pharm (Basel). 2013;6:1195–220.
Pan Y, Liang H, Liu H, Li D, Chen X, Li L, 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;192:437–46.
Wang YS, Zhou J, Hong K, Cheng XS, Li YG. MicroRNA-223 displays a protective role against cardiomyocyte hypertrophy by targeting cardiac troponin I-interacting kinase. Cell Physiol Biochem. 2015;35:1546–56.
Willeit P, Zampetaki A, Dudek K, Kaudewitz D, King A, Kirkby NS, et al. Circulating microRNAs as novel biomarkers for platelet activation. Circ Res. 2013;112:595–600.
Kadmon CS, Landers CT, Li HS, Watowich SS, Rodriguez A, King KY. MicroRNA-22 controls interferon alpha production and erythroid maturation in response to infectious stress in mice. Exp Hematol. 2017;56:7–15.
Huang WQ, Wei P, Lin RQ, Huang F. Protective effects of microrna-22 against endothelial cell injury by targeting NLRP3 through suppression of the inflammasome signaling pathway in a rat model of coronary heart disease. Cell Physiol Biochem. 2017;43:346–1358.
Gidlöf O, van der Brug M, Ohman J, Gilje P, Olde B, Wahlestedt C, et al. Platelets activated during myocardial infarction release functional miRNA, which can be taken up by endothelial cells and regulate ICAM1 expression. Blood. 2013;121:3908–17.
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;10:961–6.
Zampetaki A, Willeit P, Tilling L, Drozdov I, Prokopi M, Renard JM, et al. Prospective study on circulating microRNAs and risk of myocardial infarction. J Am Coll Cardiol. 2012;60:290–9.
Zhang YY, Zhou X, Ji WJ, Shi R, Lu RY, Li JL, 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;38:65–72.
de Boer HC, van Solingen C, Prins J, Duijs JM, Huisman MV, et al. Aspirin treatment hampers the use of plasma microRNA-126 as a biomarker for the progression of vascular disease. Eur Heart J. 2013;34:3451–7.
Cavarretta E, Chiariello GA, Condorelli G. Platelets, endothelium, and circulating microRNA-126 as a prognostic biomarker in cardiovascular diseases: per aspirin ad astra. Eur Heart J. 2013;34:3400–2.
Zampetaki A, Kiechl S, Drozdov I, Willeit P, Mayr U, Prokopi M, et al. Plasma microRNA profiling reveals loss of endothelial miR-126 and other microRNAs in type 2 diabetes. Circ Res. 2010;107:810–7.
Kaudewitz D, Skroblin P, Bender LH, Barwari T, Willeiy P, Pechlaner R, et al. Association of microRNAs and YRNAs with platelet function. Circ Res. 2016;118:420–32.
Schulte C, Molz S, Appelbaum S, Karakas M, Ojeda F, Lau DM, et al. miRNA-197 and miRNA-223 Predict cardiovascular death in a cohort of patients with symptomatic coronary artery disease. PLoS ONE. 2015;10:e0145930.
Shi R, Zhou X, Ji WJ, Zhang YY, Ma YQ, Zhang JQ, et al. The emerging role of miR-223 in platelet reactivity: implications in antiplatelet therapy. Biomed Res Int. 2015;2015:981841.
Dangwal S, Thum T. MicroRNAs in platelet biogenesis and function. Thromb Haemost. 2012;108:599–604.
Edelstein LC, Bray PF. MicroRNAs in platelet production and activation. Blood. 2011;117:5289–96.
Edelstein LC, McKenzie SE, Shaw C, Holinstat MA, Kunapuli SP, Bray PF. MicroRNAs in platelet production and activation. J Thromb Haemost. 2013;11:340–50.
Dangwal S, Thum T. MicroRNAs in platelet physiology and pathology. Hamostaseologie. 2013;33:17–20.
Kondkar AA, Bray MS, Leal SM, Nagalla S, Liu DJ, Jin Y, et al. VAMP8/endobrevin is overexpressed in hyperreactive human platelets: suggested role for platelet microRNA. J Thromb Haemost. 2010;8:369–78.
Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M, et al. 2013 ESH/ESC Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31:1281–357.
Freedman JE, Larson MG, Tanriverdi K, O'Donnell CJ, Morin K, Hakanson AS, et al. Relation of platelet and leukocyte inflammatory transcripts to body mass index in the Framingham heart study. Circulation. 2010;122:119–29.
Laffont B, Corduan A, Ple H, Duchez AC, Cloutier N, Boilard E. et al. Activated platelets can deliver mRNA regulatory Ago2•microRNA complexes to endothelial cells via microparticles. Blood. 2013;122:253–61.
Guo H, Ingolia NT, Weissman JS, Bartel DP. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature. 2010;466:835–40.
Osman A, Fälker K. Characterization of human platelet microRNA by quantitative PCR coupled with an annotation network for predicted target genes. Platelets. 2011;22:433–41.
Burt VL, Whelton P, Roccella EJ, Brown C, Cutler JA, Higgins M, et al. Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988-1991. Hypertension. 1995;25:305–13.
Taylor BC, Wilt TJ, Welch HG. Impact of diastolic and systolic blood pressure on mortality: implications for the definition of “normal”. J Gen Intern Med. 2011;26:685–90.
Benetos A, Thomas F, Bean K, Gautier S, Smulyan H, Guize L. Prognostic value of systolic and diastolic blood pressure in treated hypertensive men. Arch Intern Med. 2002;162:577–81.
Kok MG, Mandolini C, Moerland PD, de Ronde MW, Sondermeijer BM, Halliani A, et al. Low miR-19b-1-5p expression in isolated platelets after aspirin use is related to aspirin insensitivity. Int J Cardiol. 2016;203:262–3.
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Marketou, M., Kontaraki, J., Papadakis, J. et al. Platelet microRNAs in hypertensive patients with and without cardiovascular disease. J Hum Hypertens 33, 149–156 (2019). https://doi.org/10.1038/s41371-018-0123-5
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DOI: https://doi.org/10.1038/s41371-018-0123-5