Association between hypertension and circulating vascular-related microRNAs

被引:51
作者
Hijmans, Jamie G. [1 ]
Diehl, Kyle J. [1 ]
Bammert, Tyler D. [1 ]
Kavlich, Philip J. [1 ]
Lincenberg, Grace M. [1 ]
Greiner, Jared J. [1 ]
Stauffer, Brian L. [1 ,2 ,3 ]
DeSouza, Christopher A. [1 ,2 ]
机构
[1] Univ Colorado, Dept Integrat Physiol, Integrat Vasc Biol Lab, Boulder, CO 80309 USA
[2] Univ Colorado, Anschutz Med Ctr, Dept Med, Denver, CO 80262 USA
[3] Denver Hlth Med Ctr, Denver, CO 80204 USA
基金
美国国家卫生研究院;
关键词
CARDIOVASCULAR-DISEASE; DIAGNOSIS; ATHEROSCLEROSIS; BIOMARKERS; THERAPY; MIR-126; MIRNAS;
D O I
10.1038/s41371-018-0061-2
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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 (similar to 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 (similar to 50%, similar to 55%, and similar to 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.
引用
收藏
页码:440 / 447
页数:8
相关论文
共 35 条
[1]   miRNAs in atherosclerotic plaque initiation, progression, and rupture [J].
Andreou, Loannis ;
Sun, Xinghui ;
Stone, Peter H. ;
Edelman, Elazer R. ;
Feinberg, Mark W. .
TRENDS IN MOLECULAR MEDICINE, 2015, 21 (05) :307-318
[2]   MicroRNA-34a regulates cardiac ageing and function [J].
Boon, Reinier A. ;
Iekushi, Kazuma ;
Lechner, Stefanie ;
Seeger, Timon ;
Fischer, Ariane ;
Heydt, Susanne ;
Kaluza, David ;
Treguer, Karine ;
Carmona, Guillaume ;
Bonauer, Angelika ;
Horrevoets, Anton J. G. ;
Didier, Nathalie ;
Girmatsion, Zenawit ;
Biliczki, Peter ;
Ehrlich, Joachim R. ;
Katus, Hugo A. ;
Mueller, Oliver J. ;
Potente, Michael ;
Zeiher, Andreas M. ;
Hermeking, Heiko ;
Dimmeler, Stefanie .
NATURE, 2013, 495 (7439) :107-110
[3]   The role of miRNAs in cardiovascular disease risk factors [J].
Buie, Joy N. Jones ;
Goodwin, Andrew J. ;
Cook, James A. ;
Halushka, Perry V. ;
Fan, Hongkuan .
ATHEROSCLEROSIS, 2016, 254 :271-281
[4]   Circulating miR-21 and eNOS in subclinical atherosclerosis in patients with hypertension [J].
Cengiz, Mahir ;
Yavuzer, Serap ;
Avci, Burcak Kilickiran ;
Yuruyen, Mehmet ;
Yavuzer, Hakan ;
Dikici, Suleyman Atilla ;
Karatas, Omer Faruk ;
Ozen, Mustafa ;
Uzun, Hafize ;
Ongen, Zeki .
CLINICAL AND EXPERIMENTAL HYPERTENSION, 2015, 37 (08) :643-649
[5]   Differential Expression of Hypertension-Associated MicroRNAs in the Plasma of Patients With White Coat Hypertension [J].
Cengiz, Mahir ;
Karatas, Omer Faruk ;
Koparir, Erkan ;
Yavuzer, Serap ;
Ali, Chayar ;
Yavuzer, Hakan ;
Kirat, Emre ;
Karter, Yesari ;
Ozen, Mustafa .
MEDICINE, 2015, 94 (13)
[6]   MicroRNAs as pharmacological targets in endothelial cell function and dysfunction [J].
Chamorro-Jorganes, Aranzazu ;
Araldi, Elisa ;
Suarez, Yajaira .
PHARMACOLOGICAL RESEARCH, 2013, 75 :15-27
[7]   MiR-126 inhibits vascular endothelial cell apoptosis through targeting PI3K/Akt signaling [J].
Chen, Lingqiang ;
Wang, Jing ;
Wang, Bing ;
Yang, Jin ;
Gong, Zhiqiang ;
Zhao, Xueling ;
Zhang, Chunqiang ;
Du, Kaili .
ANNALS OF HEMATOLOGY, 2016, 95 (03) :365-374
[8]   Paradoxical Suppression of Atherosclerosis in the Absence of microRNA-146a [J].
Cheng, Henry S. ;
Besla, Rickvinder ;
Li, Angela ;
Chen, Zhiqi ;
Shikatani, Eric A. ;
Nazari-Jahantigh, Maliheh ;
Hammoutene, Adel ;
My-Anh Nguyen ;
Geoffrion, Michele ;
Cai, Lei ;
Khyzha, Nadiya ;
Li, Tong ;
MacParland, Sonya A. ;
Husain, Mansoor ;
Cybulsky, Myron I. ;
Boulanger, Chantal M. ;
Temel, Ryan E. ;
Schober, Andreas ;
Rayner, Katey J. ;
Robbins, Clinton S. ;
Fish, Jason E. .
CIRCULATION RESEARCH, 2017, 121 (04) :354-+
[9]   Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury [J].
Daniel, Jan-Marcus ;
Penzkofer, Daniela ;
Teske, Rebecca ;
Dutzmann, Jochen ;
Koch, Alexander ;
Bielenberg, Wiebke ;
Bonauer, Angelika ;
Boon, Reinier A. ;
Fischer, Ariane ;
Bauersachs, Johann ;
van Rooij, Eva ;
Dimmeler, Stefanie ;
Sedding, Daniel G. .
CARDIOVASCULAR RESEARCH, 2014, 103 (04) :564-572
[10]   MicroRNA-150 Modulates Ischemia-Induced Neovascularization in Atherosclerotic Conditions [J].
Desjarlais, Michel ;
Dussault, Sylvie ;
Dhahri, Wahiba ;
Mathieu, Raphael ;
Rivard, Alain .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2017, 37 (05) :900-+