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

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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access

through your institution Subscribe to this journal Receive 12 digital issues and online access to articles $119.00 per year only $9.92 per issue Learn more Buy this article * Purchase on

SpringerLink * Instant access to full article PDF Buy now Prices may be subject to local taxes which are calculated during checkout ADDITIONAL ACCESS OPTIONS: * Log in * Learn about

institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS TRANSCRIPTOME ANALYSIS OF ARTERIAL AND VENOUS CIRCULATING MIRNAS DURING

HYPERTENSION Article Open access 10 February 2021 BLOOD LEVELS OF MICRORNAS ASSOCIATED WITH ISCHEMIC HEART DISEASE DIFFER BETWEEN AUSTRIANS AND JAPANESE: A PILOT STUDY Article Open access 12

August 2020 CIRCULATING MIRNA EXPRESSION IN LONG-STANDING TYPE 1 DIABETES MELLITUS Article Open access 27 May 2023 REFERENCES * Rahimi K, Emdin CA, MacMahon S. The epidemiology of blood

pressure and its worldwide management. Circ Res. 2015;116:925–36. Article  PubMed  CAS  Google Scholar  * 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. Article  PubMed  PubMed Central  CAS  Google Scholar  * 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. Article  PubMed  Google Scholar  * Viereck J, Thum T. Circulating noncoding RNAs as biomarkers of cardiovascular disease and injury. Circ Res. 2017;120:381–99. Article 

PubMed  CAS  Google Scholar  * 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. Article  PubMed  CAS  Google Scholar  * Wronska A, Kurkowska-Jastrzebska I, Santulli G. Application of microRNAs in diagnosis

and treatment of cardiovascular disease. Acta Physiol. 2015;213:60–83. Article  CAS  Google Scholar  * 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. Article  PubMed  PubMed Central  CAS  Google Scholar  * 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. Article  PubMed  PubMed Central  CAS  Google Scholar  *

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. Article  PubMed  CAS  Google Scholar  * 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. CAS  Google Scholar  * Paterson MR, Kriegel AJ. MiR-146a/b: a family with shared seeds and different roots. Physiol Genom. 2017;49:243–52. Article 

CAS  Google Scholar  * 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. Article  PubMed  CAS  Google Scholar  * 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. Article  CAS  Google Scholar  * Fukushima Y, Nakanishi M, Nonogi H, Goto Y, Iwai N. Assessment of plasma miRNAs in congestive heart failure.

Circ J. 2011;75:336–40. Article  PubMed  CAS  Google Scholar  * 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. Article  PubMed  CAS  Google Scholar  * 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. Article  PubMed  PubMed Central  CAS  Google Scholar  * 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. Article  PubMed  PubMed Central  Google Scholar  * Singh MV, Abboud FM. Toll-like receptors and hypertension. Am J Physiol Regul Integr Comp

Physiol. 2014;307:R501–4. Article  PubMed  PubMed Central  CAS  Google Scholar  * 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. Article  PubMed  PubMed Central  CAS  Google Scholar  * 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. Article  PubMed  PubMed Central  CAS  Google Scholar  * 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. Article  PubMed  PubMed Central  CAS  Google Scholar  * John S, Schmieder RE. Potential mechanisms of impaired

endothelial function in arterial hypertension and hypercholesterolemia. Curr Hypertens Rep. 2003;5:199–207. Article  PubMed  Google Scholar  * 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. Article  PubMed  CAS  Google Scholar  * 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. Article 

PubMed  PubMed Central  CAS  Google Scholar  * Yin H, Pickering JG. Cellular senescence and vascular disease: novel routes to better understanding and therapy. Can J Cardiol. 2016;32:612–23.

Article  PubMed  Google Scholar  * 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. Article  PubMed  PubMed Central  CAS  Google Scholar  * 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. Article  PubMed  CAS  Google Scholar  * 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. Article  PubMed  CAS  Google Scholar  * 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.

Article  PubMed  CAS  Google Scholar  * 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. Article  PubMed  PubMed Central  CAS  Google Scholar  * 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.

Article  PubMed  PubMed Central  Google Scholar  * 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. Article  PubMed  CAS  Google Scholar  * 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. Article  PubMed  CAS  Google Scholar

  * 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. Download references 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. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado, Boulder, CO, 80309, USA

Jamie G. Hijmans, Kyle J. Diehl, Tyler D. Bammert, Philip J. Kavlich, Grace M. Lincenberg, Jared J. Greiner, Brian L. Stauffer & Christopher A. DeSouza * Department of Medicine, Anschutz

Medical Center, University of Colorado, Denver, CO, 80262, USA Brian L. Stauffer & Christopher A. DeSouza * Denver Health Medical Center, Denver, CO, 80204, USA Brian L. Stauffer

Authors * Jamie G. Hijmans View author publications You can also search for this author inPubMed Google Scholar * Kyle J. Diehl View author publications You can also search for this author

inPubMed Google Scholar * Tyler D. Bammert View author publications You can also search for this author inPubMed Google Scholar * Philip J. Kavlich View author publications You can also

search for this author inPubMed Google Scholar * Grace M. Lincenberg View author publications You can also search for this author inPubMed Google Scholar * Jared J. Greiner View author

publications You can also search for this author inPubMed Google Scholar * Brian L. Stauffer View author publications You can also search for this author inPubMed Google Scholar *

Christopher A. DeSouza View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Christopher A. DeSouza. ETHICS DECLARATIONS

CONFLICT OF INTEREST The authors declare that they have no conflict of interest. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE 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

Download citation * Received: 09 January 2018 * Revised: 08 February 2018 * Accepted: 15 February 2018 * Published: 04 April 2018 * Issue Date: June 2018 * DOI:

https://doi.org/10.1038/s41371-018-0061-2 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not

currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative