Abstract
microRNAs (miRNAs) have a key role in regulating inflammation, vascular health and in turn, cardiovascular disease. Specifically, altered circulating expression of miR-17, miR-21, miR-34a, miR-92a, miR-126, miR-145, miR-146a, and miR-150 has been linked with the pathogenesis and progression of cardiovascular disease. The aim of this study was to determine whether the circulating profile of these vascular-related miRNAs is disrupted with hypertension. Thirty sedentary, middle-aged adults were studied: 15 normotensive (10M/5F; age: 56 ± 1 year; BP: 113/71 ± 2/1 mmHg) and 15 hypertensive (10M/5F; 56 ± 2 year; 140/87 ± 2/2 mmHg). All subjects were non-obese and free of other cardiometabolic disorders. Circulating miRNAs were determined in plasma using standard RT-PCR techniques with miRNA primers of interest. Expression was normalized to exogenous C. elegans miR-39 and reported as relative expression in arbitrary units (AU). Circulating expression of miR-34a (9.18 ± 0.94 vs 5.33 ± 0.91 AU) was higher (~170%; P < 0.01) whereas the expression of miR-21 (1.32 ± 0.25 vs 2.50 ± 0.29 AU), miR-126 (0.85 ± 0.10 vs 1.74 ± 0.27 AU) and miR-146a (1.50 ± 0.20 vs 3.10 ± 0.50 AU) were markedly lower (~50%, ~55%, and ~55% respectively; P < 0.05) in the hypertensive vs normotensive groups. Moreover, circulating levels of miR-34a, miR-21, and miR-126 were significantly related to systolic blood pressure (r = 0.48, r = −0.38; r = −0.48); whereas, miR-146a was significantly related to both systolic (r = −0.58) and diastolic (r = −0.55) blood pressure. There were no significant group differences in circulating miR-17, miR-92a, miR-145, and miR-150. In summary, these results suggest that hypertension, independent of other cardiometabolic risk factors, adversely affects the circulating profile of a subset of vascular-related miRNAs that have been link to CVD risk and development.
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References
Rahimi K, Emdin CA, MacMahon S. The epidemiology of blood pressure and its worldwide management. Circ Res. 2015;116:925–36.
Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Himmelfarb CD et al. ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension, 2017;1-283
Diehl KJ, Weil BR, Greiner JJ, Wright KP, Stauffer BL, DeSouza CA. Impaired endogenous fibrinolytic capacity in prehypertensive men. J Hum Hypertens. 2015;29:468–72. https://doi.org/10.1038/jhh.2014.120.
Weil BR, Stauffer BL, Greiner JJ, DeSouza CA. Prehypertension is associated with impaired nitric oxide-mediated endothelium-dependent vasodilation in sedentary adults. Am J Hypertens. 2011;24:976–81.
Viereck J, Thum T. Circulating noncoding RNAs as biomarkers of cardiovascular disease and injury. Circ Res. 2017;120:381–99.
Economou EK, Oikonomou E, Siasos G, Papageorgiou N, Tsalamandris S, Mourouzis K, et al. The role of microRNAs in coronary artery disease: From pathophysiology to diagnosis and treatment. Atherosclerosis. 2015;241:624–33.
Wronska A, Kurkowska-Jastrzebska I, Santulli G. Application of microRNAs in diagnosis and treatment of cardiovascular disease. Acta Physiol. 2015;213:60–83.
Andreou I, Sun X, Stone PH, Edelman ER, Feinberg MW. miRNAs in atherosclerotic plaque initiation, progression, and rupture. Trends Mol Med. 2015;21:307–18.
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;50:298–301.
Elbehidy RM, Youssef DM, El-Shal AS, Shalaby SM, Sherbiny HS, Sherief LM, et al. MicroRNA-21 as a novel biomarker in diagnosis and response to therapy in asthmatic children. Mol Immunol. 2016;71:107–14.
Chamorro-Jorganes A, Araldi E, Suárez Y. microRNAs as pharmacological targets in endothelial cell function and dysfunction. Pharmacol Res J Ital Pharmacol Soc. 2013;75:15–27.
Paterson MR, Kriegel AJ. MiR-146a/b: a family with shared seeds and different roots. Physiol Genom. 2017;49:243–52.
Chen L, Wang J, Wang B, Yang J, Gong Z, Zhao X, et al. MiR-126 inhibits vascular endothelial cell apoptosis through targeting PI3K/Akt signaling. Ann Hematol. 2016;95:365–74.
Tang S, Wang F, Shao M, Wang Y, Zhu H. MicroRNA-126 suppresses inflammation in endothelial cells under hyperglycemic condition by targeting HMGB1. Vasc Pharmacol. 2017;88:48–55.
Fukushima Y, Nakanishi M, Nonogi H, Goto Y, Iwai N. Assessment of plasma miRNAs in congestive heart failure. Circ J. 2011;75:336–40.
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;463:60–63.
Cheng HS, Besla R, Li A, Chen Z, Shikatani EA, Nazari-Jahantigh M, et al. Paradoxical suppression of atherosclerosis in the absence of microRNA-146a. Circ Res. 2017;121:354–67.
Ma S, Tian XY, Zhang Y, Mu C, Shen H, Bismuth J, et al. E-selectin-targeting delivery of microRNAs by microparticles ameliorates endothelial inflammation and atherosclerosis. Sci Rep. 2016;6:22910. https://doi.org/10.1038/srep22910.
Singh MV, Abboud FM. Toll-like receptors and hypertension. Am J Physiol Regul Integr Comp Physiol. 2014;307:R501–4.
Maegdefessel L, Azuma J, Toh R, Deng A, Merk DR, Raiesdana A, et al. MicroRNA-21 blocks abdominal aortic aneurysm development and nicotine-augmented expansion. Sci Transl Med. 2012;4:122ra22.
McDonald RA, White KM, Wu J, Cooley BC, Robertson KE, Halliday CA, et al. miRNA-21 is dysregulated in response to vein grafting in multiple models and genetic ablation in mice attenuates neointima formation. Eur Heart J. 2013;34:1636–43.
Weber M, Baker MB, Moore JP, Searles CD. MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity. Biochem Biophys Res Commun. 2010;393:643–8.
John S, Schmieder RE. Potential mechanisms of impaired endothelial function in arterial hypertension and hypercholesterolemia. Curr Hypertens Rep. 2003;5:199–207.
Boon RA, Iekushi K, Lechner S, Seeger T, Fischer A, Heydt S, et al. MicroRNA-34a regulates cardiac ageing and function. Nature. 2013;495:107–10.
Han H, Qu G, Han C, Wang Y, Sun T, Li F, et al. MiR-34a, miR-21 and miR-23a as potential biomarkers for coronary artery disease: a pilot microarray study and confirmation in a 32 patient cohort. Exp Mol Med. 2015;47:e138.
Yin H, Pickering JG. Cellular senescence and vascular disease: novel routes to better understanding and therapy. Can J Cardiol. 2016;32:612–23.
Daniel J-M, Penzkofer D, Teske R, Dutzmann J, Koch A, Bielenberg W, et al. Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury. Cardiovasc Res. 2014;103:564–72.
Lovren F, Pan Y, Quan A, Singh KK, Shukla PC, Gupta N, et al. MicroRNA-145 targeted therapy reduces atherosclerosis. Circulation. 2012;126:S81–S90.
Desjarlais M, Dussault S, Dhahri W, Mathieu R, Rivard A. MicroRNA-150 modulates ischemia-induced neovascularization in atherosclerotic conditions. Arterioscler Thromb Vasc Biol. 2017;37:900–8.
Park MY, Herrmann SM, Saad A, Widmer RJ, Tang H, Zhu X-Y, et al. Circulating and renal vein levels of microRNAs in patients with renal artery stenosis. Nephrol Dial Transplant. 2015;30:480–90.
Jones Buie JN, Goodwin AJ, Cook JA, Halushka PV, Fan H. The role of miRNAs in cardiovascular disease risk factors. Atherosclerosis. 2016;254:271–81. https://doi.org/10.1016/j.atherosclerosis.2016.09.067.
Cengiz M, Karatas OF, Koparir E, Yavuzer S, Ali C, Yavuzer H, et al. Differential expression of hypertension-associated microRNAs in the plasma of patients with white coat hypertension. Medicine. 2015;94:e693. https://doi.org/10.1097/MD.0000000000000693.
Cengiz M, Yavuzer S, Avcı BK, Yürüyen M, Yavuzer H, Dikici SA, et al. Circulating miR-21 and eNOS in subclinical atherosclerosis in patients with hypertension. Clin Exp Hypertens. 2015;37:643–9.
Marques FZ, Campain AE, Tomaszewski M, Zukowska-Szczechowska E, Yang YHJ, Charchar FJ, et al. Gene expression profiling reveals renin mRNA overexpression in human hypertensive kidneys and a role for microRNAs. Hypertension. 2011;58:1093–8.
Nagy ZB, Barták BK, Kalmár A, Galamb O, Wichmann B, Dank M, et al. Comparison of circulating miRNAs expression alterations in matched tissue and plasma samples during colorectal cancer progression. Pathol Oncol Res 2017;1–9.
Acknowledgements
We would like to thank all subjects who participated in this study and the University of Colorado Boulder, Clinical and Translational Research Center clinical staff for their assistance.
Funding
This study was supported by the National Institutes of Health awards HL131458, HL135598, and NIH/NCATS UL1 TR001082.
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Hijmans, J.G., Diehl, K.J., Bammert, T.D. et al. Association between hypertension and circulating vascular-related microRNAs. J Hum Hypertens 32, 440–447 (2018). https://doi.org/10.1038/s41371-018-0061-2
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DOI: https://doi.org/10.1038/s41371-018-0061-2
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