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:

Maternal serum uric acid concentration is associated with the expression of tumour necrosis factor-α and intercellular adhesion molecule-1 in patients with preeclampsia

Journal of Human Hypertension volume 30, pages 456–462 (2016)Cite this article

Subjects

Abstract

We aimed to investigate whether there is a correlation between elevated serum uric acid (SUA) concentration and endothelial inflammatory response in women with preeclampsia (PE). On the basis of clinical and laboratory findings, patients were assigned to three groups: normal blood pressure (Control (Con)), gestational hypertension (GH) and PE (n=50 in each group). SUA concentration was measured by spectrophotometry, and serum tumour necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1) levels were measured by enzyme-linked immunosorbent assay. Western blotting and immunohistochemical staining were also used to detect the changes in TNF-α and ICAM-1 expression in subcutaneous fat tissue. PE patients showed significantly higher systolic and diastolic blood pressures compared with Con and GH pregnant women (P=0.02 and P=0.02, respectively). The changes of body mass index (ΔBMI) before and after pregnancy and 24-h urine protein were significantly different among the three groups (P<0.001). Maternal SUA, TNF-α and soluble ICAM-1 (sICAM-1) levels were significantly increased in the patients with PE (P<0.05) compared with the other two groups. Scatterplot analysis revealed that elevated SUA concentration positively correlated with TNF-α and sICAM-1 in pregnant women. Moreover, vessels in subcutaneous fat tissues of preeclamptic patients showed intense TNF-α and ICAM-1 staining compared with Con and GH patients. The results support that, to a certain extent, elevated SUA concentration is significantly associated with inflammation of maternal systemic vasculature as indicated by increased TNF-α and ICAM-1 expression in women with PE.

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
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Yakoob MY . Vitamin D deficiency during pregnancy and the risk of preeclampsia. J Pak Med Assoc 2011; 61 (8): 827–828.

    PubMed  Google Scholar 

  2. Shalom G, Shoham-Vardi I, Sergienko R, Wiznitzer A, Sherf M, Sheiner E . Is preeclampsia a significant risk factor for long-term hospitalizations and morbidity? J Matern Fetal Neonatal Med 2013; 26 (1): 13–15.

    Article  Google Scholar 

  3. Osol G, Bernstein I . Preeclampsia and maternal cardiovascular disease: consequence or predisposition? J Vasc Res 2014; 51 (4): 290–304.

    Article  CAS  Google Scholar 

  4. Amaral LM, Cunningham MW Jr, Cornelius DC, LaMarca B . Preeclampsia: long-term consequences for vascular health. Vasc Health Risk Manag 2015; 11: 403–415.

    PubMed  PubMed Central  Google Scholar 

  5. Chu NF, Wang DJ, Liou SH, Shieh SM . Relationship between hyperuricemia and other cardiovascular disease risk factors among adult males in Taiwan. Eur J Epidemiol 2000; 16: 13–17.

    Article  CAS  Google Scholar 

  6. Gouri A, Dekaken A, Bentorki AA, Touaref A, Yekhlef A, Sekkache F et al. Serum uric acid level and cardiovascular risks in hemodialysis patients: an Algerian cohort study. Pak J Biol Sci 2013; 16: 852–858.

    Article  CAS  Google Scholar 

  7. Wu Y, Xiong X, Fraser WD, Luo ZC . Association of uric acid with progression to preeclampsia and development of adverse conditions in gestational hypertensive pregnancies. Am J Hypertens 2012; 25: 711–717.

    Article  CAS  Google Scholar 

  8. Terkeltaub R . Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol 2010; 6 (1): 30–38.

    Article  CAS  Google Scholar 

  9. Bo S, Gambino R, Durazzo M, Ghione F, Musso G, Gentile L et al. Associations between serum uric acid and adipokines, markers of inflammation, and endothelial dysfunction. J Endocrinol Invest 2008; 31: 499–504.

    Article  CAS  Google Scholar 

  10. Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA . Uric acid and oxidative stress. Curr Pharm Des 2005; 11: 4145–4151.

    Article  CAS  Google Scholar 

  11. Kushiyama A, Tanaka K, Hara S, Kawazu S . Linking uric acid metabolism to diabetic complications. World J Diabetes 2014; 5 (6): 787–795.

    Article  Google Scholar 

  12. Leyva F, Anker SD, Godsland IF, Teixeira M, Hellewell PG, Kox WJ et al. Uric acid in chronic heart failure: a marker of chronic inflammation. Eur Heart J 1998; 19: 1814–1822.

    Article  CAS  Google Scholar 

  13. Ramji DP, Davies TS . Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets. Cytokine Growth Factor Rev e-pub ahead of print 12 May 2015 ..

  14. Campbell LA, Rosenfeld ME . Infection and atherosclerosis development. Arch Med Res 2015; 46 (5): 339–350.

    Article  CAS  Google Scholar 

  15. Münzel T, Sinning C, Post F, Warnholtz A, Schulz E . Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction. Ann Med 2008; 40: 180–196.

    Article  Google Scholar 

  16. Witkowska AM . Soluble ICAM-1: a marker of vascular inflammation and lifestyle. Cytokine 2005; 31 (2): 127–134.

    Article  CAS  Google Scholar 

  17. Rothlein R, Dustin ML, Marlin SD, Springer TA . A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol 1986; 137: 1270–1274.

    CAS  PubMed  Google Scholar 

  18. Veltman-Verhulst SM, van Rijn BB, Westerveld HE, Franx A, Bruinse HW, Fauser BC et al. Polycystic ovary syndrome and early-onset preeclampsia: reproductive manifestations of increased cardiovascular risk. Menopause 2010; 17 (5): 990–996.

    Article  Google Scholar 

  19. Pruthi D, Khankin EV, Blanton RM, Aronovitz M, Burke SD, McCurley A et al. Exposure to experimental preeclampsia in mice enhances the vascular response to future injury. Hypertension 2015; 65 (4): 863–870.

    Article  CAS  Google Scholar 

  20. Kessous R, Shoham-Vardi I, Pariente G, Sergienko R, Sheiner E . Long-term maternal atherosclerotic morbidity in women with pre-eclampsia. Heart 2015; 101 (6): 442–446.

    Article  Google Scholar 

  21. Scantlebury DC, Hayes SN . How does preeclampsia predispose to future cardiovascular disease? Curr Hypertens Rep 2014; 16 (9): 472.

    Article  Google Scholar 

  22. American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013; 122: 1122–1131.

    Article  Google Scholar 

  23. Dumesnil JG, Dion D, Yvorchuk K, Davies RA, Chan K . A new, simple and accurate method for determining ejection fraction by Doppler echocardiography. Can J Cardiol 1995; 11: 1007–1014.

    CAS  PubMed  Google Scholar 

  24. Apgar V . A proposal for a new method of evaluation of the newborn infant. Curr Res Anesth Analg 1953; 32: 260–267.

    Article  CAS  Google Scholar 

  25. Martell-Claros N, Blanco-Kelly F, Abad-Cardiel M, Torrejón MJ, Alvarez- Alvarez B, Fuentes ME et al. Early predictors of gestational hypertension in a low-risk cohort. Results of a pilot study. J Hypertens 2013; 31: 2380–2385.

    Article  CAS  Google Scholar 

  26. Bellomo G, Venanzi S, Saronio P, Verdura C, Narducci PL . Prognostic significance of serum uric acid in women with gestational hypertension. Hypertension 2011; 58: 704–708.

    Article  CAS  Google Scholar 

  27. Jeyabalan A, Conrad KP . Renal function during normal pregnancy and preeclampsia. Front Biosci 2007; 12: 2425–2437.

    Article  CAS  Google Scholar 

  28. Powers RW, Bodnar LM, Ness RB, Cooper KM, Gallaher MJ, Frank MP et al. Uric acid concentrations in early pregnancy among preeclamptic women with gestational hyperuricemia at delivery. Am J Obstet Gynecol 2006; 194 (1): 160.

    Article  CAS  Google Scholar 

  29. Kang DH, Finch J, Nakagawa T, Karumanchi SA, Kanellsi J, Granger J et al. Uric acid, endothelial dysfunction and pre-eclampsia: searching for a pathogenetic link. J Hypertens 2004; 22: 229–235.

    Article  CAS  Google Scholar 

  30. Laughon SK, Catov J, Roberts JM . Uric acid concentrations are associated with insulin resistance and birthweight in normotensive pregnant women. Am J Obstet Gynecol 2009; 201: 582e1–582e6.

    Article  Google Scholar 

  31. Leik CE, Walsh SW . Neutrophils infiltrate resistance-sized vessels of subcutaneous fat in women with preeclampsia. Hypertension 2004; 44 (1): 72–77.

    Article  CAS  Google Scholar 

  32. López-Jaramillo P, Herrera JA, Arenas-Mantilla M, Jáuregui IE, Mendoza MA . Subclinical infection as a cause of inflammation in preeclampsia. Am J Ther 2008; 15 (4): 373–376.

    Article  Google Scholar 

  33. Jin YC, Kim CW, Kim YM, Nizamutdinova IT, Ha YM, Kim HJ et al. Cryptotanshinone, a lipophilic compound of Salvia miltiorrriza root, inhibits TNF-alpha-induced expression of adhesion molecules in HUVEC and attenuates rat myocardial ischemia/reperfusion injury in vivo. Eur J Pharmacol 2009; 614: 91–97.

    Article  CAS  Google Scholar 

  34. True AL, Rahman A, Malik AB . Activation of NF-kappaB induced by H2O2 and TNF-alpha and its effects on ICAM-1 expression in endothelial cells. Am J Physiol Lung Cell Mol Physiol 2000; 279: L302–L311.

    Article  CAS  Google Scholar 

  35. Fan HC, Fernández-Hernando C, Lai JH . Protein kinase C isoforms in atherosclerosis: pro- or anti-inflammatory? Biochem Pharmacol 2014; 88: 139–149.

    Article  CAS  Google Scholar 

  36. Lim S, Park S . Role of vascular smooth muscle cell in the inflammation of atherosclerosis. BMB Rep 2014; 47: 1–7.

    Article  Google Scholar 

  37. Gersch C, Palii SP, Kim KM, Angerhofer A, Johnson RJ, Henderson GN . Inactivation of nitric oxide by uric acid. Nucleosides Nucleotides Nucleic Acids 2008; 27: 967–978.

    Article  CAS  Google Scholar 

  38. Zharikov S, Krotova K, Hu H, Baylis C, Johnson RJ, Block ER et al. Uric acid decreases NO production and increases arginase activity in cultured pulmonary artery endothelial cells. Am J Physiol Cell Physiol 2008; 295: C1183–C1190.

    Article  CAS  Google Scholar 

  39. Staff AC, Dechend R, Pijnenborg R . Learning from the placenta: acute atherosis and vascular remodeling in preeclampsia-novel aspects for atherosclerosis and future cardiovascular health. Hypertension 2010; 56 (6): 1026–1034.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank two anonymous reviewers for very valuable comments which improved the quality of this manuscript. We also thank Prof. Feng-Yu Sun for assistance with the statistical analyses in this manuscript. This study was supported by Heilongjiang Returned Overseas Foundation (No. LC2011C13), National Natural Science Foundation of China (No. 81301276) and the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry.

Author contributions

JZ and DYZ designed the experiment; LS, XGY, JMY, XTZ and MW carried out the patient enrolment, data collection and follow-up. XTZ and MW participated and carried out all the experiments such as ELISA, western blotting and IHC. JZ and DYZ performed the statistical analyses and drafted the manuscript. All authors read and approved the revised manuscript.

Author information

Author notes

  1. J Zhao and D-Y Zheng: These authors contributed equally to the work.

Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin, PR China

    J Zhao, M Wang, X-T Zhang & L Sun

  2. Department of Anesthesiology, The Second Affiliated Hospital, Harbin Medical University, Harbin, PR China

    D-Y Zheng

  3. Department of Cardiology Ultrasound, The First Affiliated Hospital, Harbin Medical University, Harbin, PR China

    J-M Yang

  4. Department of Obstetrics, The First Affiliated Hospital, Harbin Medical University, Harbin, PR China

    X-G Yun

Authors
  1. J Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D-Y Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J-M Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. X-T Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. L Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. X-G Yun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J Zhao.

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

Zhao, J., Zheng, DY., Yang, JM. et al. Maternal serum uric acid concentration is associated with the expression of tumour necrosis factor-α and intercellular adhesion molecule-1 in patients with preeclampsia. J Hum Hypertens 30, 456–462 (2016). https://doi.org/10.1038/jhh.2015.110

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/jhh.2015.110

This article is cited by

Search

Advanced search

Quick links