Skip to main content

Advertisement

Log in

Serum sFlt-1, cystatin C and cathepsin B are potential severity markers in preeclampsia: a pilot study

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Preeclampsia is associated with abnormal invasion of the trophoblast through decidua and subsequently altered remodeling of the maternal spiral arteries and endothelial dysfunction. This phenomenon is explained by the dysregulation of various kinds of vascular factors and proteases. The purpose of this study was to compare the circulating levels of sFlt-1, cathepsin B, and cystatin C in preeclamptic and normotensive pregnancies.

Study design

Sixty-two pregnant women were enrolled in this prospective study. Twenty women were preeclamptic and 42 were normotensive. Serum levels of sFlt-1, cathepsin B, and cystatin C were measured using an enzyme-linked immunosorbent assay kit.

Results

Circulating levels of sFlt-1, cathepsin B, and cystatin C were significantly higher in preeclamptic than in normotensive pregnant women (p < 0.001; p = 0.017; p = 0.003). Preeclamptic women with severe features demonstrated significantly higher levels of cathepsin B (p = 0.05). Serum sFlt-1 and cystatin C levels were positively correlated with elevated systolic and diastolic blood pressure. The levels of cathepsin B were positively correlated with alanine and aspartate aminotransferase. The amount of 24 h proteinuria was positively, but non-significantly correlated with sFlt-1 and cystatin C.

Conclusions

In addition to sFlt-1 levels, the serum levels of cathepsin B and cystatin C significantly change when preeclampsia develops. These markers are associated with severity markers of elevated blood pressure and liver injury in preeclampsia.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

sFlt-1:

Soluble fms-like tyrosine kinase

PlGF:

Placental growth factor

SBP:

Systolic blood pressure

DBP:

Diastolic blood pressure

BMI:

Body mass index

SGA:

Small for gestational age

AGA:

Appropriate for gestational age

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

References

  1. N.H.I.S.Y.S. Korea (2017) Health insurance review and assessment service

  2. Roberts JM, Pearson GD, Cutler JA, Lindheimer MD, National Heart L, Blood I (2003) Summary of the NHLBI working group on research on hypertension during pregnancy. Hypertens Pregnancy 22(2):109–127

    Article  Google Scholar 

  3. Varanou A, Withington SL, Lakasing L, Williamson C, Burton GJ, Hemberger M (2006) The importance of cysteine cathepsin proteases for placental development. J Mol Med (Berl) 84(4):305–317

    Article  CAS  Google Scholar 

  4. Kim HY, Kim BW, Kim YJ (2016) Elevated serum cathepsin B concentration in pregnant women is associated with preeclampsia. Arch Gynecol Obstet 294(6):1145–1150

    Article  CAS  Google Scholar 

  5. Kim HY, Baek HS (2019) Circulating cathepsin B and D in pregnancy. J Obstet Gynaecol 39(1):17–21

    Article  CAS  Google Scholar 

  6. ACOG Practice Bulletin No (2019) 202: gestational hypertension and preeclampsia. Obstet Gynecol 133(1):e1–e25

    Article  Google Scholar 

  7. Mehra S, Kumar M, Manchanda M, Singh R, Thakur B, Rani N, Arava S, Narang R, Arya DS, Chauhan SS (2017) Clinical significance of cathepsin L and cathepsin B in dilated cardiomyopathy. Mol Cell Biochem 428(1–2):139–147

    Article  CAS  Google Scholar 

  8. Buhling F, Rocken C, Brasch F, Hartig R, Yasuda Y, Saftig P, Bromme D, Welte T (2004) Pivotal role of cathepsin K in lung fibrosis. Am J Pathol 164(6):2203–2216

    Article  Google Scholar 

  9. Mohamed MM, Sloane BF (2006) Cysteine cathepsins: multifunctional enzymes in cancer. Nat Rev Cancer 6(10):764–775

    Article  CAS  Google Scholar 

  10. Reiser J, Adair B, Reinheckel T (2010) Specialized roles for cysteine cathepsins in health and disease. J Clin Invest 120(10):3421–3431

    Article  CAS  Google Scholar 

  11. Baskin-Bey ES, Canbay A, Bronk SF, Werneburg N, Guicciardi ME, Nyberg SL, Gores GJ (2005) Cathepsin B inactivation attenuates hepatocyte apoptosis and liver damage in steatotic livers after cold ischemia-warm reperfusion injury. Am J Physiol Gastrointest Liver Physiol 288(2):G396–G402

    Article  CAS  Google Scholar 

  12. Manchanda M, Das P, Gahlot GPS, Singh R, Roeb E, Roderfeld M, Datta Gupta S, Saraya A, Pandey RM, Chauhan SS (2017) Cathepsin L and B as potential markers for liver fibrosis: insights from patients and experimental models. Clin Transl Gastroenterol 8(6):e99

    Article  CAS  Google Scholar 

  13. Canbay A, Guicciardi ME, Higuchi H, Feldstein A, Bronk SF, Rydzewski R, Taniai M, Gores GJ (2003) Cathepsin B inactivation attenuates hepatic injury and fibrosis during cholestasis. J Clin Invest 112(2):152–159

    Article  CAS  Google Scholar 

  14. Feldstein AE, Werneburg NW, Canbay A, Guicciardi ME, Bronk SF, Rydzewski R, Burgart LJ, Gores GJ (2004) Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway. Hepatology 40(1):185–194

    Article  CAS  Google Scholar 

  15. Ng QJ, Han JY, Saffari SE, Yeo GS, Chern BSM, Tan KH (2019) Longitudinal circulating placental growth factor (PlGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1) concentrations during pregnancy in Asian women: a prospective cohort study. BMJ Open 9(5):e028321

    Article  Google Scholar 

  16. Abbas AM, Fikry EM, Mostafa TS, Shaltout AS, El-Baz MAH (2018) Prognostic value of serum soluble FMS-like tyrosine kinase (sFlt-1) levels in pre-eclampsia and eclampsia; a prospective cohort study. Hypertens Pregnancy 37(3):137–143

    Article  CAS  Google Scholar 

  17. Afonso S, Tovar C, Romagnano L, Babiarz B (2002) Control and expression of cystatin C by mouse decidual cultures. Mol Reprod Dev 61(2):155–163

    Article  CAS  Google Scholar 

  18. Turk V, Stoka V, Turk D (2008) Cystatins: biochemical and structural properties, and medical relevance. Front Biosci 13:5406–5420

    Article  CAS  Google Scholar 

  19. Kristensen K, Lindstrom V, Schmidt C, Blirup-Jensen S, Grubb A, Wide-Swensson D, Strevens H (2007) Temporal changes of the plasma levels of cystatin C, beta-trace protein, beta2-microglobulin, urate and creatinine during pregnancy indicate continuous alterations in the renal filtration process. Scand J Clin Lab Invest 67(6):612–618

    Article  CAS  Google Scholar 

  20. Yalcin S, Ulas T, Eren MA, Aydogan H, Camuzcuoglu A, Kucuk A, Yuce HH, Demir ME, Vural M, Aksoy N (2013) Relationship between oxidative stress parameters and cystatin C levels in patients with severe preeclampsia. Medicina (Kaunas) 49(3):118–123

    Google Scholar 

  21. Wakasugi K, Nakano T, Morishima I (2004) Association of human neuroglobin with cystatin C, a cysteine proteinase inhibitor. Biochemistry 43(18):5119–5125

    Article  CAS  Google Scholar 

  22. Cunningham FG (2018) Williams obstetrics, 25th edn. McGrawHill education, New York

    Google Scholar 

  23. Costa RA, Hoshida MS, Alves EA, Zugaib M, Francisco RP (2016) Preeclampsia and superimposed preeclampsia: the same disease? The role of angiogenic biomarkers. Hypertens Pregnancy 35(2):139–149

    Article  CAS  Google Scholar 

Download references

Funding

This study was supported by a Korea University Ansan Hospital Grant (O1801301).

Author information

Authors and Affiliations

Authors

Contributions

YSP: Protocol development, Manuscript writing, Data collection. YK: Data collection, Manuscript writing. HYK: Project development, Data analysis, Manuscript editing. KHA: Data management, Manuscript editing. GJC: Data analysis, Manuscript editing. SCH: Manuscript supervision. MJO: Manuscript supervision. HJK: Data collection, Manuscript editing.

Corresponding author

Correspondence to Ho Yeon Kim.

Ethics declarations

Conflict of interest

All authors declare no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, Y.S., Kim, Y., Kim, H.Y. et al. Serum sFlt-1, cystatin C and cathepsin B are potential severity markers in preeclampsia: a pilot study. Arch Gynecol Obstet 301, 955–962 (2020). https://doi.org/10.1007/s00404-020-05478-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-020-05478-6

Keywords

Navigation