Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

The circulating level of miR-122 is a potential risk factor for endothelial dysfunction in young patients with essential hypertension

Hypertension Research volume 43, pages 511–517 (2020)Cite this article

Abstract

MicroRNAs are key molecules involved in the regulation of endothelial function. They are important risk factors and biomarkers for the development of hypertension related to endothelial dysfunction. However, the gene expression patterns associated with hypertension development related to endothelial dysfunction have not been fully elucidated. We conducted a case-control study of 65 patients with essential hypertension (EH) and 61 controls without EH. Plasma levels of miR-122 and its target protein high-affinity cationic amino acid transporter 1 (CAT-1) were measured by qRT-PCR and ELISA, respectively. miR-122 expression in plasma of patients with EH was significantly higher than that of the control group (p = 0.001), while CAT-1 expression in patients with EH was significantly lower than that in the control group (p = 0.018). miR-122 expression in plasma of young patients with EH was significantly higher than that in young people without EH (p = 0.0004), and CAT-1 expression in plasma of young patients with EH was also significantly lower than that of the control group (p = 0.002). CAT-1 expression in the plasma of young participants was significantly higher than that of individuals aged ≥40 years (p = 0.003), whereas miR-122 expression was significantly lower (p = 0.001). We showed that among patients with EH, the high expression of miR-122 contributed to endothelial dysfunction by suppressing the expression of the CAT-1 protein, which led to a decrease in CAT-1 expression in plasma. Therefore, high expression of miR-122 appears to be a risk factor for endothelial dysfunction in EH, especially in younger patients.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Moon JY, Park KJ, Hwangbo Y, Lee MR, Yoo BI, Won JH, et al. A trend analysis of the prevalence, awareness, treatment, and control of hypertension by age group. J Prev Med Public Health. 2013;46:353–9.

    Article  Google Scholar 

  2. Zhang Y, Moran AE. Trends in the prevalence, awareness, treatment, and control of hypertension among young adults in the United States, 1999 to 2014. Hypertension. 2017;70:736–42.

    Article  CAS  Google Scholar 

  3. Romaine SPR, Charchar FJ, Samani NJ, Tomaszewski M. Circulating microRNAs and hypertension-from new insights into blood pressure regulation to biomarkers of cardiovascular risk. Curr Opin Pharm. 2016;27:1–7.

    Article  CAS  Google Scholar 

  4. Chang J, Nicolas E, Marks D, Sander C, Lerro A, Buendia MA, et al. miR-122, a mammalian liver-specific miRNA, is processed from hcr mRNA and may downregulate the high affinity cationic amino acid transporter CAT-1. RNA Biol. 2005;1:106–13.

    Article  Google Scholar 

  5. Valdmanis PN, Kim HK, Chu K, Zhang F, Xu J, Munding EM, et al. miR-122 removal in the liver activates imprinted microRNAs and enables more effective microRNA mediated gene repression. Nat Commun. 2018;9:5321.

    Article  CAS  Google Scholar 

  6. Yang Z, Venardos K, Jones E, Morris BJ, Dusting JC, Kaye DM. Identification of a novel polymorphism in the 3′UTR of the contribution to hypertension and endothelial dysfunction. Circulation. 2007;115:1269–74.

    Article  CAS  Google Scholar 

  7. Yang Z, Kaye DM. Mechanistic insights into the link between a polymorphism of the 3´UTR of the SLC7A1 gene and hypertension. Hum Mutat. 2009;30:328–33.

    Article  Google Scholar 

  8. Schlaich MP, Parnell MM, Ahlers BA, Finch S, Marshall T, Zhang WZ, et al. Impaired L-arginine transport and endothelial function in hypertensive and genetically predisposed normotensive subjects. Circulation. 2004;110:3680–86.

    Article  CAS  Google Scholar 

  9. Chin-Dusting JP, Willems L, Kaye DM. L-Arginine transporters in cardiovascular disease: a novel therapeutic target. Pharm Ther. 2007;116:428–36.

    Article  CAS  Google Scholar 

  10. Klimczak D, Jazdzewski K, Kuch M. Regulatory mechanisms in arterial hypertension: role of microRNA in pathophysiology and therapy. Blood Press. 2017;1:2–8.

    Article  Google Scholar 

  11. Li X, Wei Y, Wang Z. microRNA-21 and hypertension. Hypertens Res. 2018;41:649–61.

    Article  CAS  Google Scholar 

  12. Coulouarn C, Factor VM, Andersen JB, Durkin ME, Thorgeirsson SS. Loss of miR-122 expression in liver cancer correlates with suppression of the hepatic phenotype and gain of metastatic properties. Oncogene. 2009;40:3526–36.

    Article  Google Scholar 

  13. 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;13:e693.

    Article  Google Scholar 

  14. Zhou X, Wang J, Fa Y, Ye H. Signature microRNA expression profile is associated with spontaneous hypertension in African green monkey. Clin Exp Hypertens. 2019;3:287–91.

    Article  Google Scholar 

  15. Naveed A, ur-Rahman S, Abdullah S, Naveed MA. A concise review of microRNA exploring the insights of microRNA regulations in bacterial, viral and metabolic diseases. Mol Biotechnol. 2017;59:518–29.

    Article  CAS  Google Scholar 

  16. Konstantinidis G, Head GA, Evans RG, Nguyen-Huu TP, Venardos K, Croft KD, et al. Endothelial cationic amino acid transporter-1 overexpression can prevent oxidative stress and increases in arterial pressure in response to superoxide dismutase inhibition in mice. Acta Physiol. 2014;4:845–53.

    Article  Google Scholar 

  17. Rajapakse NW, Mattson DL. Role of L-arginine in nitric oxide production in health and hypertension. Clin Exp Pharm Physiol. 2008;3:249–55.

    Google Scholar 

  18. Rajapaksea NW, Mattson DL. Role of cellular L-arginine uptake and nitric oxide production on renal blood flow and arterial pressure regulation. Curr Opin Nephrol Hypertens. 2013;1:45–50.

    Article  Google Scholar 

Download references

Acknowledgements

We thank Dr Jianxing Yu and Prof. Jingmei Jiang for their help with statistical assessments.

Funding

This work was supported by grants from the CAMS Initiative for Innovative Medicine (2016-I2M-3–006).

Author information

Authors and Affiliations

  1. Institute of Microcirculation, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, China

    Hong-Gang Zhang, Qiu-Ju Zhang, Bing-Wei Li, Lu-Han Li, Xiao-Hong Song, Jian-Qun Han & Rui-Juan Xiu

  2. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100037, China

    Chang-Ming Xiong, Yu-Bao Zou & Bing-Yang Liu

Authors
  1. Hong-Gang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qiu-Ju Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bing-Wei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lu-Han Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xiao-Hong Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Chang-Ming Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yu-Bao Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bing-Yang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jian-Qun Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Rui-Juan Xiu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hong-Gang Zhang.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the Ethics Committee at the Institute of Microcirculation at the Chinese Academy of Medical Sciences (CAMS; Beijing, China) and Peking Union Medical College (PUMC; Beijing, China). The study adhered to the tenets of the Declaration of Helsinki as well as applicable Chinese laws.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, HG., Zhang, QJ., Li, BW. et al. The circulating level of miR-122 is a potential risk factor for endothelial dysfunction in young patients with essential hypertension. Hypertens Res 43, 511–517 (2020). https://doi.org/10.1038/s41440-020-0405-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41440-020-0405-5

Keywords

This article is cited by

Search

Advanced search

Quick links