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.

MMP-9 and miR-181a-5p in serum and placenta are associated with adverse outcomes of patients with severe preeclampsia and their infants

Abstract

This study explored the correlation of MMP-9 with miR-181a-5p in severe preeclampsia (SPE). Placental tissues and serum were collected from 30 pregnant SPE patients (aged 29.42 ± 3.75) and 30 normal pregnant women (aged 27.72 ± 2.21), followed by detecting MMP-9 and miR-181a-5p fold changes using RT-qPCR, and grouped as follows: high expression groups (≥median value): H-MMP-9 and H-miR-181a-5p vs. low expression groups (<median value): L-MMP-9 and L-miR-181a-5p. MMP-9 was weakly expressed (F = 709.99, p < 0.001; F = 670.45, p < 0.001) (serum: 0.41 ± 0.06 (fold changes); placenta: 0.42 ± 0.09 (fold changes)), whereas miR-181a-5p was highly expressed (F = 284.93, p < 0.001; F = 353.78, p < 0.001) (serum: 2.26 ± 0.39; placenta: 2.02 ± 0.29) in SPE patients. MMP-9 was negatively correlated with miR-181a-5p (serum: r = −0.5767, p = 0.0009; placenta: r = −0.5667, p = 0.0011) in SPE patients. MMP-9 showed positive-correlation with gestational week at delivery (r = 0.7625; p < 0.0001) and infant weight (r = 0.4947; p < 0.0001) of SPE patients. miR-181-5p showed negative-correlation (gestational week at delivery: r = −0.5614, p = 0.0012; infant weight: r = −0.4081, p = 0.0252). H-MMP-9 group had lower adverse outcome than L-MMP-9 group (p = 0.0006), and H-miR-181a-5p group had higher adverse outcome than L-miR-181a-5p group (p = 0.0036). In brief, MMP-9 was negatively correlated with miR-181a-5p in serum and placenta of SPE patients. MMP-9 and miR-181a-5p affected gestational week at delivery and infant weight, providing novel targets for SPE treatment.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Fig. 1: Expressions of MMP-9 and miR-181a-5p in the serum and placenta of SPE patients and women with normal pregnancy.
Fig. 2: Correlation of MMP-9 with miR-181a-5p in  the serum and placenta of SPE patients.
Fig. 3: Correlation of MMP-9 and miR-181a-5p with a gestational week at delivery and infant weight.
Fig. 4: MMP-9 and miR-181a-5p were correlated with adverse outcomes of SPE patients and infants.

Data and materials availability

All the data generated or analyzed during this study are included in this published article.

References

  1. Pankiewicz K, Fijalkowska A, Issat T, Maciejewski TM. Insight into the key points of preeclampsia pathophysiology: uterine artery remodeling and the role of MicroRNAs. Int J Mol Sci. 2021;22:3132.

  2. Vigil-De Gracia P, Ludmir J. The use of magnesium sulfate for women with severe preeclampsia or eclampsia diagnosed during the postpartum period. J Matern Fetal Neonatal Med. 2015;28:2207–9.

    Article  Google Scholar 

  3. Ray A, Ray S. Epidural therapy for the treatment of severe pre-eclampsia in non labouring women. Cochrane Database Syst Rev. 2017;11:CD009540.

    PubMed  Google Scholar 

  4. Arulkumaran N, Lightstone L. Severe pre-eclampsia and hypertensive crises. Best Pract Res Clin Obstet Gynaecol. 2013;27:877–84.

    CAS  Article  Google Scholar 

  5. Ferreira I, Peeters LL, Stehouwer CD. Preeclampsia and increased blood pressure in the offspring: meta-analysis and critical review of the evidence. J Hypertens. 2009;27:1955–9.

    CAS  Article  Google Scholar 

  6. Pasaribu HP, Hariman H, Roeshadi RH, Koh SC. Soluble vascular cell adhesion molecule-1 and magnesium sulfate with nifedipine treatment in Indonesian women with severe pre-eclampsia. Inter Med Appl Sci. 2016;8:97–102.

    Google Scholar 

  7. Shen M, Smith GN, Rodger M, White RR, Walker MC, Wen SW. Comparison of risk factors and outcomes of gestational hypertension and pre-eclampsia. PLoS One. 2017;12:e0175914.

    Article  Google Scholar 

  8. WHO recommendations: Policy of interventionist versus expectant management of severe pre-eclampsia before term: Geneva, 2018.

  9. Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol. 2018;141:1202–7.

    CAS  Article  Google Scholar 

  10. Skalis G, Katsi V, Miliou A, Georgiopoulos G, Papazachou O, Vamvakou G, et al. MicroRNAs in preeclampsia. Microrna. 2019;8:28–35.

    CAS  Article  Google Scholar 

  11. Lv Y, Lu C, Ji X, Miao Z, Long W, Ding H, et al. Roles of microRNAs in preeclampsia. J Cell Physiol. 2019;234:1052–61.

    CAS  Article  Google Scholar 

  12. Gusar V, Timofeeva A, Chagovets V, Kan N, Vasilchenko O, Prozorovskaya K et al. Preeclampsia: the interplay between oxygen-sensitive mirnas and erythropoietin. J Clin Med 2020;9:574.

  13. Huang X, Wu L, Zhang G, Tang R, Zhou X. Elevated MicroRNA-181a-5p contributes to trophoblast dysfunction and preeclampsia. Reprod Sci. 2019;26:1121–9.

    CAS  Article  Google Scholar 

  14. Chen J, Khalil RA. Matrix metalloproteinases in normal pregnancy and preeclampsia. Prog Mol Biol Transl Sci. 2017;148:87–165.

    CAS  Article  Google Scholar 

  15. Espino YSS, Flores-Pliego A, Espejel-Nunez A, Medina-Bastidas D, Vadillo-Ortega F, Zaga-Clavellina V et al. New insights into the role of matrix metalloproteinases in preeclampsia. Int J Mol Sci 2017;18:1448.

  16. Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;72:24–43.

    CAS  Article  Google Scholar 

  17. Gottardi E, Lecarpentier E, Villette C, Berman A, Redel D, Tsatsaris V, et al. Preeclampsia before 26 weeks of gestation: obstetrical prognosis for the subsequent pregnancy. J Gynecol Obstet Hum Reprod. 2021;50:102000.

    Article  Google Scholar 

  18. Takahashi N, Li F, Fushima T, Oyanagi G, Sato E, Oe Y, et al. Vitamin B3 nicotinamide: a promising candidate for treating preeclampsia and improving fetal growth. Tohoku J Exp Med. 2018;244:243–8.

    CAS  Article  Google Scholar 

  19. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–8.

    CAS  Article  Google Scholar 

  20. Abraham C, Kusheleva N. Management of pre-eclampsia and eclampsia: a simulation. MedEdPORTAL. 2019;15:10832.

    Article  Google Scholar 

  21. Vashukova ES, Glotov AS, Fedotov PV, Efimova OA, Pakin VS, Mozgovaya EV, et al. Placental microRNA expression in pregnancies complicated by superimposed preeclampsia on chronic hypertension. Mol Med Rep. 2016;14:22–32.

    CAS  Article  Google Scholar 

  22. Feng H, Wang L, Zhang M, Zhang Z, Guo W, Wang X. Ratio of matrix metalloproteinase-2 to -9 is a more accurate predictive biomarker in women with suspected pre-eclampsia. Biosci Rep. 2017;37:BSR20160508.

    CAS  Article  Google Scholar 

  23. Poon LC, Shennan A, Hyett JA, Kapur A, Hadar E, Divakar H, et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: a pragmatic guide for first-trimester screening and prevention. Int J Gynaecol Obstet. 2019;145:1–33. Suppl 1

    Article  Google Scholar 

  24. Nascimento RA, Possomato-Vieira JS, Bonacio GF, Rizzi E, Dias-Junior CA. Reductions of circulating nitric oxide are followed by hypertension during pregnancy and increased activity of matrix metalloproteinases-2 and -9 in rats. Cells 2019;8:1402.

  25. Laskowska M. Altered maternal serum matrix metalloproteinases MMP-2, MMP-3, MMP-9, and MMP-13 in severe early- and late-onset preeclampsia. Biomed Res Int. 2017;2017:6432426.

    Article  Google Scholar 

  26. Zhu A, Chu L, Ma Q, Li Y. Long non-coding RNA H19 down-regulates miR-181a to facilitate endothelial angiogenic function. Artif Cells Nanomed Biotechnol. 2019;47:2698–705.

    CAS  Article  Google Scholar 

  27. Basu J, Agamasu E, Bendek B, Salafia CM, Mishra A, Lopez JV, et al. Correlation between placental matrix metalloproteinase 9 and tumor necrosis factor-alpha protein expression throughout gestation in normal human pregnancy. Reprod Sci. 2018;25:621–7.

    CAS  Article  Google Scholar 

  28. Johannsson E, Henriksen T, Iversen PO. Increase in matrix metalloproteinases from endothelial cells exposed to umbilical cord plasma from high birth weight newborns. Am J Physiol Regul Integr Comp Physiol. 2007;292:R1563–8.

    CAS  Article  Google Scholar 

  29. Hromadnikova I, Kotlabova K, Krofta L A. History of preterm delivery is associated with aberrant postpartal MicroRNA expression profiles in mothers with an absence of other pregnancy-related complications. Int J Mol Sci 2021;22:4033.

  30. Poon LC, Nekrasova E, Anastassopoulos P, Livanos P, Nicolaides KH. First-trimester maternal serum matrix metalloproteinase-9 (MMP-9) and adverse pregnancy outcome. Prenat Diagn. 2009;29:553–9.

    CAS  Article  Google Scholar 

  31. Yao Y, Robinson AM, Zucchi FC, Robbins JC, Babenko O, Kovalchuk O, et al. Ancestral exposure to stress epigenetically programs preterm birth risk and adverse maternal and newborn outcomes. BMC Med. 2014;12:121.

    Article  Google Scholar 

  32. Nissi R, Talvensaari-Mattila A, Kotila V, Niinimaki M, Jarvela I, Turpeenniemi-Hujanen T. Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure. Reprod Biol Endocrinol. 2013;11:2.

    CAS  Article  Google Scholar 

  33. Hromadnikova I, Kotlabova K, Dvorakova L, Krofta L. Postpartum profiling of microRNAs involved in pathogenesis of cardiovascular/cerebrovascular diseases in women exposed to pregnancy-related complications. Int J Cardiol. 2019;291:158–67.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Y.J.Z., L.W. contributed to the study concepts, study design, and definition of intellectual content; F.F.N. contributed to the literature research; Y.J.Z., L.W., F.F.N., Y.Y.L. contributed to the manuscript preparation and L.F. contributed to the manuscript editing and review; Y.J.Z., L.W., F.F.N. contributed to the experimental studies and data acquisition; Y.Y.L., L.F. contributed to the data analysis and statistical analysis. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Lin Feng.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics statement

This study strictly followed the Declaration of Helsinki and was approved by the Ethics Committee of Shengli Oilfield Central Hospital. All subjects signed informed consent forms before participating 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

Verify currency and authenticity via CrossMark

Cite this article

Zheng, Y., Wang, L., Niu, F. et al. MMP-9 and miR-181a-5p in serum and placenta are associated with adverse outcomes of patients with severe preeclampsia and their infants. J Hum Hypertens (2022). https://doi.org/10.1038/s41371-021-00643-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41371-021-00643-z

Search

Quick links