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.

  • Original Article
  • Published:

Plasma expression level of miRNA let-7 is positively correlated with carotid intima-media thickness in patients with essential hypertension

Journal of Human Hypertension volume 31, pages 843–847 (2017)Cite this article

Subjects

Abstract

MicroRNAs (miRNA, miR) play vital part in the pathophysiology of arterial remodeling in hypertension patients, and are increasingly becoming novel biomarkers in cardiovascular disease. The study was designed to evaluate the correlation between let-7 expression level and subclinical atherosclerosis in untreated patients with newly diagnosed essential hypertension. We assessed 240 participants including 60 healthy volunteers with normal carotid intima-media thickness (nCIMT), 60 healthy volunteers with increased CIMT (iCIMT), 60 hypertension patients with nCIMT and 60 hypertension patients with iCIMT. All patients underwent measurements of CIMT and ambulatory blood pressure (BP) monitoring. The level of let-7 was quantified using real-time reverse transcription polymerase chain reaction. Correlations of let-7 expression with BP parameters and CIMT were assessed using multiple linear regression analysis. We observed the lowest miRNA let-7 expression (21.70±1.45 vs 29.33±2.58 vs 31.50±1.80 vs 35.49±2.33; P<0.001) in healthy controls with nCIMT, followed by healthy controls with iCIMT, then hypertension patients with nCIMT and highest expression in hypertension patients with iCIMT. Let-7 was independently correlated with CIMT(r=0.587, P<0.001), and multiple linear regression analysis showed that let-7 was independently correlated with CIMT (β=0.031, P<0.001). Our findings provide significant evidence that plasma let-7 could represent a non-invasive marker for atherosclerosis in hypertensive patients and herald the emergence of a potential indicator to monitor end-organ damage in hypertension.

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

Figure 1

Similar content being viewed by others

References

  1. Leung AA, Nerenberg K, Daskalopoulou SS, McBrien K, Zarnke KB, Dasgupta K et al. Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Can J Cardiol 2016; 32 (5): 569–588.

    Article  Google Scholar 

  2. Fleg JL, Forman DE, Berra K, Bittner V, Blumenthal JA, Chen MA et al. Secondary prevention of atherosclerotic cardiovascular disease in older adults: a scientific statement from the American Heart Association. Circulation 2013; 128 (22): 2422–2446.

    Article  Google Scholar 

  3. Stein JH, Korcarz CE, Post WS . Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: summary and discussion of the American Society of Echocardiography consensus statement. Prev Cardiol 2009; 12 (1): 34–38.

    Article  Google Scholar 

  4. Guo H, Ingolia NT, Weissman JS, Bartel DP . Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature 2010; 466 (7308): 835–840.

    Article  CAS  Google Scholar 

  5. Kumar S, Kim CW, Simmons RD, Jo H . Role of flow-sensitive microRNAs in endothelial dysfunction and atherosclerosis: mechanosensitive athero-miRs. Arterioscler Thromb Vasc Biol 2014; 34 (10): 2206–2216.

    Article  CAS  Google Scholar 

  6. Nazari-Jahantigh M, Wei Y, Noels H, Akhtar S, Zhou Z, Koenen RR et al. MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages. J Clin Invest 2012; 122 (11): 4190–4202.

    Article  CAS  Google Scholar 

  7. Zhang XR, Fu XJ, Zhu DS, Zhang CZ, Hou S, Li M et al. Salidroside-regulated lipid metabolism with down-regulation of miR-370 in type 2 diabetic mice. Eur J Pharmacol 2016; 779: 46–52.

    Article  CAS  Google Scholar 

  8. Zhao C, Popel AS . Computational Model of MicroRNA Control of HIF-VEGF Pathway: Insights into the Pathophysiology of Ischemic Vascular Disease and Cancer. Plos Comput Biol 2015; 11 (11): e1004612–e1004640.

    Article  Google Scholar 

  9. Li S, Zhu J, Zhang W, Chen Y, Zhang K, Popescu LM et al. Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection. Circulation 2011; 124 (2): 175–184.

    Article  CAS  Google Scholar 

  10. Kin K, Miyagawa S, Fukushima S, Shirakawa Y, Torikai K, Shimamura K et al. Tissue- and plasma-specific MicroRNA signatures for atherosclerotic abdominal aortic aneurysm. J Am Heart Assoc 2012; 1 (5): e745–e755.

    Article  Google Scholar 

  11. Su JL, Chen PS, Johansson G, Kuo ML . Function and regulation of let-7 family microRNAs. Microrna 2012; 1 (1): 34–39.

    Article  CAS  Google Scholar 

  12. Katayama M, Sjogren RJ, Egan B, Krook A . miRNA let-7 expression is regulated by glucose and TNF-alpha by a remote upstream promoter. Biochem J 2015; 472 (2): 147–156.

    Article  CAS  Google Scholar 

  13. Zhu H, Shyh-Chang N, Segre AV, Shinoda G, Shah SP, Einhorn WS et al. The Lin28/let-7 axis regulates glucose metabolism. Cell 2011; 147 (1): 81–94.

    Article  CAS  Google Scholar 

  14. Liao YC, Wang YS, Guo YC, Lin WL, Chang MH, Juo SH . Let-7g improves multiple endothelial functions through targeting transforming growth factor-beta and SIRT-1 signaling. J Am Coll Cardiol 2014; 63 (16): 1685–1694.

    Article  CAS  Google Scholar 

  15. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Bohm M et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J 2013; 34 (28): 2159–2219.

    Article  Google Scholar 

  16. Cardellini M, Marini MA, Frontoni S, Hribal ML, Andreozzi F, Perticone F et al. Carotid artery intima-media thickness is associated with insulin-mediated glucose disposal in nondiabetic normotensive offspring of type 2 diabetic patients. Am J Physiol Endocrinol Metab 2007; 292 (1): E347–E352.

    Article  CAS  Google Scholar 

  17. Bonny A, Lacombe F, Yitemben M, Discazeaux B, Donetti J, Fahri P et al. The 2007 ESH/ESC guidelines for the management of arterial hypertension. J Hypertens 2008; 26 (4): 825 825-826.

    Article  CAS  Google Scholar 

  18. Huang Y, Chen J, Zhou Y, Yu X, Huang C, Li J et al. Circulating miR-30 is related to carotid artery atherosclerosis. Clin Exp Hypertens 2016; 38 (5): 489–494.

    Article  CAS  Google Scholar 

  19. Huang Y, Chen J, Zhou Y, Tang S, Li J, Yu X et al. Circulating miR155 expression level is positive with blood pressure parameters: Potential markers of target-organ damage. Clin Exp Hypertens 2016; 38 (3): 331–336.

    Article  CAS  Google Scholar 

  20. Sayed D, Hong C, Chen IY, Lypowy J, Abdellatif M . MicroRNAs play an essential role in the development of cardiac hypertrophy. Circ Res 2007; 100 (3): 416–424.

    Article  CAS  Google Scholar 

  21. Huang Y, Tang S, Ji-Yan C, Huang C, Li J, Cai AP et al. Circulating miR-92a expression level in patients with essential hypertension: a potential marker of atherosclerosis. J Hum Hypertens 2017; 31 (3): 200–205.

    Article  CAS  Google Scholar 

  22. Nguyen LH, Zhu H . Lin28 and let-7 in cell metabolism and cancer. Transl Pediatr 2015; 4 (1): 4–11.

    PubMed  PubMed Central  Google Scholar 

  23. Bao MH, Feng X, Zhang YW, Lou XY, Cheng Y, Zhou HH . Let-7 in cardiovascular diseases, heart development and cardiovascular differentiation from stem cells. Int J Mol Sci 2013; 14 (11): 23086–23102.

    Article  Google Scholar 

  24. Perlini S, Grassi G . Hypertension-related target organ damage: is it a continuum? J Hypertens 2013; 31 (6): 1083–1085.

    Article  CAS  Google Scholar 

  25. Wang D, Wang J, Jin C, Ji R, Wang A, Li X et al. Asymptomatic Extracranial Artery Stenosis and the Risk of Cardiovascular and Cerebrovascular Diseases. Sci Rep 2016; 6: 33960–33966.

    Article  CAS  Google Scholar 

  26. Pirro M, Stingeni L, Vaudo G, Mannarino MR, Ministrini S, Vonella M et al. Systemic inflammation and imbalance between endothelial injury and repair in patients with psoriasis are associated with preclinical atherosclerosis. Eur J Prev Cardiol 2015; 22 (8): 1027–1035.

    Article  Google Scholar 

  27. Cheng G, Fan F, Zhang Y, Qi L, Jia J, Liu Y et al. Different associations between blood pressure indices and carotid artery damages in a community-based population of China. J Hum Hypertens 2016; 30 (12): 750–754.

    Article  CAS  Google Scholar 

  28. Condorelli G, Latronico MV, Cavarretta E . microRNAs in cardiovascular diseases: current knowledge and the road ahead. J Am Coll Cardiol 2014; 63 (21): 2177–2187.

    Article  CAS  Google Scholar 

  29. Frost RJ, Olson EN . Control of glucose homeostasis and insulin sensitivity by the Let-7 family of microRNAs. Proc Natl Acad Sci USA 2011; 108 (52): 21075–21080.

    Article  CAS  Google Scholar 

  30. Ragab SM, Safan MA, Obeid OM, Sherief AS . Lipoprotein-associated phospholipase A2 (Lp-PLA2) and tumor necrosis factor-alpha (TNF-alpha) and their relation to premature atherosclerosis in beta-thalassemia children. Hematology 2015; 20 (4): 228–238.

    Article  CAS  Google Scholar 

  31. Song L, Li D, Gu Y, Li X, Peng L . Let-7a modulates particulate matter (&lt;/=2.5 mum)-induced oxidative stress and injury in human airway epithelial cells by targeting arginase 2. J Appl Toxicol 2016; 36 (10): 1302–1310.

    Article  CAS  Google Scholar 

  32. Li J, Ren Y, Shi E, Tan Z, Xiong J, Yan L et al. Inhibition of the Let-7 Family MicroRNAs Induces Cardioprotection Against Ischemia-Reperfusion Injury in Diabetic Rats. Ann Thorac Surg 2016; 102 (3): 829–835.

    Article  Google Scholar 

  33. Yamazoe M, Hisamatsu T, Miura K, Kadowaki S, Zaid M, Kadota A et al. Relationship of Insulin Resistance to Prevalence and Progression of Coronary Artery Calcification Beyond Metabolic Syndrome Components: Shiga Epidemiological Study of Subclinical Atherosclerosis. Arterioscler Thromb Vasc Biol 2016; 36 (8): 1703–1708.

    Article  CAS  Google Scholar 

  34. Long G, Wang F, Duan Q, Yang S, Chen F, Gong W et al. Circulating miR-30a, miR-195 and let-7b associated with acute myocardial infarction. PLoS ONE 2012; 7 (12): e50926–e50934.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank all the participating volunteers for their efforts and contributions. This study was funded from Guangdong Natural Science Foundation (No. S2013010016575, No. 2015A030313660), Technology Project Foundation of Guangzhou (No. 2014y2-00140, No. 1563000381), Technology Project Foundation of Guangdong Province (No. 2014B020212008) and the National Natural Science Foundation of China (No. 81300230).

Author information

Authors and Affiliations

  1. Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

    Y-q Huang, C Huang, J-y Chen, J Li & Y-q Feng

Authors
  1. Y-q Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J-y Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y-q Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y-q Feng.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Huang, Yq., Huang, C., Chen, Jy. et al. Plasma expression level of miRNA let-7 is positively correlated with carotid intima-media thickness in patients with essential hypertension. J Hum Hypertens 31, 843–847 (2017). https://doi.org/10.1038/jhh.2017.52

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2017.52

This article is cited by

Search

Advanced search

Quick links