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:

Circ_0000284: A risk factor and potential biomarker for prehypertension and hypertension

Hypertension Research volume 46, pages 720–729 (2023)Cite this article

Abstract

CircRNAs have been shown to be involved in the development of certain diseases, but their application in prehypertension and hypertension remains unclear. We aimed to explore the potential role of circ_0000284 in revealing the molecular regulatory mechanisms of prehypertension and hypertension. We enrolled a total of 100 patients with normal blood pressure, 100 patients with prehypertension and 100 patients with hypertension. The expression of circ_0000284 among the groups was detected by real-time fluorescence quantitative polymerase chain reaction (qRT‒PCR). Multivariate logistic models were constructed combining conventional risk factors with circ_0000284. A receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of circRNAs in the clinical model. Spearman correlation was used to analyze the correlation of circ_0000284 and the biochemical characteristics of all subjects. The results showed that circ_0000284 was differentially expressed among the normal blood pressure group, prehypertensive group and hypertensive group and showed a significantly upregulated trend in the progression to hypertension (P < 0.05). The ROC curve revealed a high diagnostic ability of circ_0000284 in hypertension in the clinical model (AUC = 0.812). Circ_0000284 also presented a certain ability for early diagnosis of prehypertension (AUC = 0.628). Spearman correlation showed that circ_0000284 was positively correlated with Na and CKMB. Our study suggested that upregulated expression of circ_0000284 was an independent risk factor for prehypertension and hypertension. Circ_0000284 was a potential fingerprint for the early diagnosis of hypertension and distinguished the intermediate stage of hypertension development. Moreover, our study provided new insight into the correlation between circ_0000284 and cardiac injury in the progression to hypertension.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, et al. Global burden of cardiovascular diseases and risk factors, 1990-2019: Update from the GBD 2019 study. J Am Coll Cardiol. 2020;76:2982–3021.

    Article  Google Scholar 

  2. Diseases GBD, Injuries C. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396:1204–22.

    Article  Google Scholar 

  3. Poulter NR, Prabhakaran D, Caulfield M. Hypertension. Lancet. 2015;386:801–12.

    Article  Google Scholar 

  4. Lawes CM, Vander Hoorn S, Law MR, Elliott P, MacMahon S, Rodgers A. Blood pressure and the global burden of disease 2000. Part II: estimates of attributable burden. J Hypertens. 2006;24:423–30.

    Article  CAS  Google Scholar 

  5. Luo D, Cheng Y, Zhang H, Ba M, Chen P, Li H, et al. Association between high blood pressure and long-term cardiovascular events in young adults: Systematic review and meta-analysis. BMJ 2020;370:m3222.

    Article  Google Scholar 

  6. Bigazzi R, Zagato L, Lanzani C, Fontana S, Messaggio E, Delli Carpini S, et al. Hypertension in high school students: Genetic and environmental factors: The HYGEF Study. Hypertension. 2020;75:71–8.

    Article  CAS  Google Scholar 

  7. Li Z, Fu C, Yang F, Mao Z. Prevalence and risk factors of hypertension for the middle-aged population in China - results from the China Health and Retirement Longitudinal Study (CHARLS). Clin Exp Hypertens. 2019;41:80–6.

    Article  Google Scholar 

  8. Leung AA, Bushnik T, Hennessy D, McAlister FA, Manuel DG. Risk factors for hypertension in Canada. Health Rep. 2019;30:3–13.

    Google Scholar 

  9. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, et al. Seventh report of the Joint National committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003;42:1206–52.

    Article  CAS  Google Scholar 

  10. Egan BM, Stevens-Fabry S. Prehypertension-prevalence, health risks, and management strategies. Nat Rev Cardiol. 2015;12:289–300.

    Article  Google Scholar 

  11. Han M, Li Q, Liu L, Zhang D, Ren Y, Zhao Y, et al. Prehypertension and risk of cardiovascular diseases: a meta-analysis of 47 cohort studies. J Hypertens. 2019;37:2325–32.

    Article  CAS  Google Scholar 

  12. Ishikawa Y, Ishikawa J, Ishikawa S, Kario K, Kajii E. Jichi Medical School Cohort Investigators G. Progression from prehypertension to hypertension and risk of cardiovascular disease. J Epidemiol. 2017;27:8–13.

    Article  Google Scholar 

  13. Bai Q, Peng B, Wu X, Cao Y, Sun X, Hong M, et al. Metabolomic study for essential hypertension patients based on dried blood spot mass spectrometry approach. IUBMB Life. 2018;70:777–85.

    Article  CAS  Google Scholar 

  14. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495:384–8.

    Article  CAS  Google Scholar 

  15. Li R, Jiang J, Shi H, Qian H, Zhang X, Xu W. CircRNA: A rising star in gastric cancer. Cell Mol Life Sci. 2020;77:1661–80.

    Article  CAS  Google Scholar 

  16. Lim TB, Lavenniah A, Foo RS. Circles in the heart and cardiovascular system. Cardiovasc Res. 2020;116:269–78.

    CAS  Google Scholar 

  17. Li M, Duan L, Li Y, Liu B. Long noncoding RNA/circular noncoding RNA-miRNA-mRNA axes in cardiovascular diseases. Life Sci. 2019;233:116440.

    Article  CAS  Google Scholar 

  18. Shan K, Liu C, Liu BH, Chen X, Dong R, Liu X, et al. Circular noncoding RNA HIPK3 mediates retinal vascular dysfunction in Diabetes Mellitus. Circulation. 2017;136:1629–42.

    Article  CAS  Google Scholar 

  19. Wang Y, Zhao R, Liu W, Wang Z, Rong J, Long X, et al. Exosomal circHIPK3 released from hypoxia-pretreated cardiomyocytes regulates oxidative damage in cardiac microvascular endothelial cells via the miR-29a/IGF-1 Pathway. Oxid Med Cell Longev. 2019;2019:7954657.

    Article  Google Scholar 

  20. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The Seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: The JNC 7 report. JAMA. 2003;289:2560–72.

    Article  CAS  Google Scholar 

  21. Collaborators GBDRF. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990-2017: A systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1923–94.

  22. Bao X, He X, Zheng S, Sun J, Luo Y, Tan R, et al. Up-regulation of circular RNA hsa_circ_0037909 promotes essential hypertension. J Clin Lab Anal. 2019;33:e22853.

    Article  Google Scholar 

  23. Song X, Zhang N, Han P, Moon BS, Lai RK, Wang K, et al. Circular RNA profile in gliomas revealed by identification tool UROBORUS. Nucleic Acids Res. 2016;44:e87.

    Article  Google Scholar 

  24. Wang K, Long B, Liu F, Wang JX, Liu CY, Zhao B, et al. A circular RNA protects the heart from pathological hypertrophy and heart failure by targeting miR-223. Eur Heart J. 2016;37:2602–11.

    Article  CAS  Google Scholar 

  25. Zheng Q, Bao C, Guo W, Li S, Chen J, Chen B, et al. Circular RNA profiling reveals an abundant circHIPK3 that regulates cell growth by sponging multiple miRNAs. Nat Commun. 2016;7:11215.

    Article  CAS  Google Scholar 

  26. Zhang Y, Liu Q, Liao Q. CircHIPK3: A promising cancer-related circular RNA. Am J Transl Res. 2020;12:6694–704.

    CAS  Google Scholar 

  27. Wang S, Hu Y, Lv X, Li B, Gu D, Li Y, et al. Circ-0000284 arouses malignant phenotype of cholangiocarcinoma cells and regulates the biological functions of peripheral cells through cellular communication. Clin Sci (Lond). 2019;133:1935–53.

    Article  CAS  Google Scholar 

  28. Xie B, Zhang C, Kang K, Jiang S. miR-599 inhibits vascular smooth muscle cells proliferation and migration by targeting TGFB2. PLoS One. 2015;10:e0141512.

    Article  Google Scholar 

  29. Jia G, Aroor AR, Jia C, Sowers JR. Endothelial cell senescence in aging-related vascular dysfunction. Biochim Biophys Acta Mol Basis Dis. 2019;1865:1802–9.

    Article  CAS  Google Scholar 

  30. Nussenzweig SC, Verma S, Finkel T. The role of autophagy in vascular biology. Circ Res. 2015;116:480–8.

    Article  CAS  Google Scholar 

  31. Khan S, Jha A, Panda AC, Dixit A. Cancer-associated circRNA-miRNA-mRNA regulatory networks: A meta-analysis. Front Mol Biosci. 2021;8:671309.

    Article  CAS  Google Scholar 

  32. Cuspidi C, Facchetti R, Bombelli M, Tadic M, Sala C, Grassi G, et al. High normal blood pressure and left ventricular hypertrophy Echocardiographic findings from the PAMELA population. Hypertension. 2019;73:612–9.

    Article  CAS  Google Scholar 

  33. Izzo R, Mancusi C, de Simone G. Are we underestimating prehypertension? Hypertension. 2019;73:541–2.

    Article  CAS  Google Scholar 

  34. Wang TJ, Gona P, Larson MG, Levy D, Benjamin EJ, Tofler GH, et al. Multiple biomarkers and the risk of incident hypertension. Hypertension 2007;49:432–8.

    Article  CAS  Google Scholar 

  35. Velagaleti RS, Gona P, Larson MG, Wang TJ, Levy D, Benjamin EJ, et al. Multimarker approach for the prediction of heart failure incidence in the community. Circulation. 2010;122:1700–6.

    Article  Google Scholar 

  36. Lawler PR, Hiremath P, Cheng S. Cardiac target organ damage in hypertension: insights from epidemiology. Curr Hypertens Rep. 2014;16:446.

    Article  Google Scholar 

  37. Franco M, Martinez F, Rodriguez-Iturbe B, Johnson RJ, Santamaria J, Montoya A, et al. Angiotensin II, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension. Am J Physiol Ren Physiol. 2006;291:F1281–7.

    Article  CAS  Google Scholar 

  38. Liu L, Wang C, Sun D, Jiang S, Li H, Zhang W, et al. Calhex(2)(3)(1) Ameliorates cardiac hypertrophy by inhibiting cellular autophagy in vivo and in vitro. Cell Physiol Biochem. 2015;36:1597–612.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the support and cooperation of patients in sample collection. The study was approved by the ethics committee of Fujian Medical University School (No. 11, March 9, 2018).

Funding

This research was supported by the Natural Science Foundation of Fujian (2019J01315) and the Joint Funds for the Innovation of Science and Technology, Fujian Province (2018Y9089).

Author information

Author notes

  1. These authors contributed equally: Mingjun Chen, Yingying Cai, Jianhui Guo

Authors and Affiliations

  1. Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350122, China

    Mingjun Chen, Yingying Cai, Jianhui Guo, Xingyan Xu, Yawen Lin, Yuduan Hu, Yeying Wen, Le Yang & Siying Wu

  2. Department of Developmental and Behavioral Pediatrics, Fujian Children’s Hospital, Fuzhou, 350001, China

    Yingying Cai

  3. Department of General Practice, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China

    Yiran Gong & Qunfang Xie

  4. Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou, 350122, China

    Huangyuan Li

  5. The Center of Health Management, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, China

    Qunfang Xie

Authors
  1. Mingjun Chen
    View author publications

    Search author on:PubMed Google Scholar

  2. Yingying Cai
    View author publications

    Search author on:PubMed Google Scholar

  3. Jianhui Guo
    View author publications

    Search author on:PubMed Google Scholar

  4. Yiran Gong
    View author publications

    Search author on:PubMed Google Scholar

  5. Xingyan Xu
    View author publications

    Search author on:PubMed Google Scholar

  6. Yawen Lin
    View author publications

    Search author on:PubMed Google Scholar

  7. Yuduan Hu
    View author publications

    Search author on:PubMed Google Scholar

  8. Yeying Wen
    View author publications

    Search author on:PubMed Google Scholar

  9. Le Yang
    View author publications

    Search author on:PubMed Google Scholar

  10. Huangyuan Li
    View author publications

    Search author on:PubMed Google Scholar

  11. Qunfang Xie
    View author publications

    Search author on:PubMed Google Scholar

  12. Siying Wu
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Wu, Xie, and Li were responsible for the concept and design of this study. Chen, Cai, and Guo were responsible for the analysis and drafting of the manuscript. Gong, Xu, Lin, Hu, Wen, and Yang were responsible for collecting data.

Corresponding authors

Correspondence to Huangyuan Li, Qunfang Xie or Siying Wu.

Ethics declarations

Conflict of interest

The authors declare no competing interests.

Additional information

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, M., Cai, Y., Guo, J. et al. Circ_0000284: A risk factor and potential biomarker for prehypertension and hypertension. Hypertens Res 46, 720–729 (2023). https://doi.org/10.1038/s41440-022-01140-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41440-022-01140-7

Keywords

Search

Advanced search

Quick links