Skip to main content
SpringerLink
Log in

Elevated hyaluronan and extracellular matrix metalloproteinase inducer levels in women with preeclampsia

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

Abstract

Purpose

Preeclampsia (PE) is a specific syndrome of pregnancy clinically identified by hypertension and proteinuria from the 20th week of gestation associated with a systemic inflammatory response and oxidative stress. While pro-inflammatory cytokines have been extensively studied in PE, other factors in the circulation that also influence the magnitude of inflammation have received much less attention. The present study compared serum concentrations of five immune-regulatory compounds in normotensive pregnant women and in women with gestational hypertension (GH) or PE.

Methods

Sixty women with PE, 53 with GH and 40 normotensive women paired by gestational age were evaluated. Sera were evaluated for concentrations of extracellular matrix metalloproteinase inducer (EMMPRIN), hyaluronan, gelsolin, visfatin and histone 2B by ELISA. Differences between groups were analyzed by nonparametric tests, with a significance level of 5 %.

Results

Increased levels of EMMPRIN and hyaluronan were present in preeclamptic women as compared to the GH and normotensive groups. There was no difference between groups in gelsolin, visfatin or histone 2B.

Conclusion

Increased release of EMMPRIN and hyaluronan may contribute to an elevated pro-inflammatory response and tissue damage in women with PE.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Carty DM, Delles C, Dominiczak AF (2010) Preeclampsia and future maternal health. J Hypertens 28:1349–1355

    Article  CAS  PubMed  Google Scholar 

  2. Uzan J, Carbonnel M, Piconne O, Asmar R, Ayoubi JM (2011) Pre-eclampsia: pathophysiology, diagnosis and management. Vasc Health Risk Manag 7:467–474

    PubMed Central  PubMed  Google Scholar 

  3. Rein DT, Breidenbach M, Hönsheid B, Friebe-Hoffmann U, Engel H, Göhring UJ, Uekermann L, Kurbacher CM, Schöndorf T (2003) Preeclamptic women are deficient of interleukin-10 as assessed by cytokine release of trophoblast cells in vitro. Cytokine 23:119–125

    Article  CAS  PubMed  Google Scholar 

  4. Paternoster DM, Fantinato S, Manganelli F, Nicolini U, Milani M, Girolami A (2004) Recent progress in the therapeutic management of pre-eclampsia. Expert Opin Pharmacother 5:2233–2239

    Article  CAS  PubMed  Google Scholar 

  5. Pijnenborg R, Bland JM, Robertson WB, Brosens I (1983) Uteroplacental arterial changes related to interstitial trophoblast migration in early human pregnancy. Placenta 4:397–413

    Article  CAS  PubMed  Google Scholar 

  6. Khan F, Belch JJ, MacLeod M, Mires G (2005) Changes in endothelial function precede the clinical disease in women in whom preeclampsia develops. Hypertension 46:1123–1128

    Article  CAS  PubMed  Google Scholar 

  7. Dekker GA, Sibai BM (1999) The immunology of preeclampsia. Semin Perinatol 23:24–33

    Article  CAS  PubMed  Google Scholar 

  8. Gupta S, Agarwal A, Sharma RK (2005) The role of placental oxidative stress and lipid peroxidation in preeclampsia. Obstet Gynecol Surv 60:807–816

    Article  PubMed  Google Scholar 

  9. Redman CW, Sargent IL (2000) Placental debris, oxidative stress and pre-eclampsia. Placenta 21:597–602

    Article  CAS  PubMed  Google Scholar 

  10. Redman CW, Sargent IL (2005) Latest advances in understanding preeclampsia. Science 308:1592–1594

    Article  CAS  PubMed  Google Scholar 

  11. Redman CW, Sargent IL (2003) Preeclampsia, the placenta and the maternal systemic inflammatory response—a review. Placenta 24(suppl A):S21–S27

    Article  PubMed  Google Scholar 

  12. Huet E, Gabison EE, Mourah S, Menashi S (2008) Role of Emmprin/CD147 in tissue remodeling. Connect Tissue Res 49:175–179

    Article  CAS  PubMed  Google Scholar 

  13. Yuan W, Ge H, He B (2010) Pro-inflammatory activities induced by CyPA-EMMPRIN interaction in monocytes. Atherosclerosis 213:415–421

    Article  CAS  PubMed  Google Scholar 

  14. Taylor KR, Trowbridge JM, Rudisill JA, Termeer CC, Simon JC, Gallo RL (2004) Hyaluronan fragments stimulate endothelial recognition of injury through TLR4. J Biol Chem 279:17079–17084

    Article  CAS  PubMed  Google Scholar 

  15. Scheibner KA, Lutz MA, Boodoo S, Fenton MJ, Powell JD, Horton MR (2006) Hyaluronan fragments act as an endogenous danger signal by engaging TLR2. J Immunol 177:1272–1281

    CAS  PubMed  Google Scholar 

  16. Stern R, Asari AA, Sugahara KN (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85:699–715

    Article  CAS  PubMed  Google Scholar 

  17. Lee WM, Galbraith RM (1992) The extracellular actin-scavenger system and actin toxicity. N Engl J Med 326:1335–1341

    Article  CAS  PubMed  Google Scholar 

  18. Peddada N, Sagar A, Ashish, Garg R (2012) Plasma gelsolin: a general prognostic marker for health. Med Hypotheses 78:203–210

    Article  CAS  PubMed  Google Scholar 

  19. Lind SE, Janmey PA (1984) Human plasma gelsolin binds to fibronectin. J Biol Chem 259:13262–13266

    CAS  PubMed  Google Scholar 

  20. Osborn TM, Dahlgren C, Hartwig JH, Stossel TP (2007) Modifications of cellular responses to lysophosphatidic acid (LPA) and platelet activating factor (PAF) by plasma gelsolin (pGSN). Am J Physiol 292:1323–1331

    Article  Google Scholar 

  21. Bucki R, Georges PC, Espinassous Q, Funaki M, Pastore JJ, Chaby R, Janmey PA (2005) Inactivation of endotoxin by human plasma gelsolin. Biochemistry 44:9590–9597

    Article  CAS  PubMed  Google Scholar 

  22. Bucki R, Byfield FJ, Kulakowska A, McCormick ME, Drozdowski W, Namiot Z, Hartung T, Janmey PA (2008) Extracellular gelsolin binds lipoteichoic acid and modulates cellular response to proinflammatory bacterial wall components. J Immunol 181:4936–4944

    CAS  PubMed  Google Scholar 

  23. Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, Tilg H (2007) Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol 178:1748–1758

    CAS  PubMed  Google Scholar 

  24. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, Matsuki Y, Murakami M, Ichisaka T, Murakami H, Watanabe E, Takagi T, Akiyoshi M, Ohtsubo T, Kihara S, Yamashita S, Makishima M, Funahashi T, Yamanaka S, Hiramatsu R, Matsuzawa Y, Shimomura I (2005) Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 307:426–430

    Article  CAS  PubMed  Google Scholar 

  25. Fasshauer M, Waldeyer T, Seeger J, Schrey S, Ebert T, Kratzsch J, Lossner U, Bluher M, Stumvoll M, Faber R, Stepan H (2008) Serum levels of the adipokine visfatin are increased in pre-eclampsia. Clin Endocrinol 69:69–73

    Article  CAS  Google Scholar 

  26. Kim HS, Cho JH, Park HW, Yoon H, Kim MS, Kim SC (2002) Endotoxin-neutralizing antimicrobial proteins of the human placenta. J Immunol 168:2356–2364

    CAS  PubMed  Google Scholar 

  27. Witkin SS, Linhares IM, Bongiovanni AM, Herway C, Skupski D (2011) Unique alterations in infection-induced immune activation during pregnancy. BJOG 118:145–153

    Article  CAS  PubMed  Google Scholar 

  28. American College of Obstetricians and Gynecologists (2002) Diagnosis and management of preeclampsia and eclampsia. ACOG Practice Bulletin no. 33. Washington, DC

  29. Peraçoli MT, Bannwart CF, Cristofalo R, Borges VT, Costa RA, Witkin SS, Peraçoli JC (2011) Increased reactive oxygen species and tumor necrosis factor-alpha production by monocytes are associated with elevated levels of uric acid in pre-eclamptic women. Am J Reprod Immunol 66:460–467

    Article  PubMed  Google Scholar 

  30. Giorgi VS, Peracoli MT, Peracoli JC, Witkin SS, Bannwart-Castro CF (2012) Silibinin modulates the NF-κB pathway and pro-inflammatory cytokine production by mononuclear cells from preeclamptic women. J Reprod Immunol 95:67–72

    Article  CAS  PubMed  Google Scholar 

  31. Berg S, Engman A, Holmgren S, Lundahl T, Laurent TC (2001) Increased plasma hyaluronan in severe pre-eclampsia and eclampsia. Scand J Clin Lab Invest 61:131–137

    Article  CAS  PubMed  Google Scholar 

  32. Fraser JR, Laurent TC, Laurent UB (1997) Hyaluronan: its nature, distribution, functions and turnover. J Intern Med 242:27–33

    Article  CAS  PubMed  Google Scholar 

  33. Wilson MC, Meredth D, Fox JE, Manoharan C, Davies AJ, Halestrap AP (2005) Basigin (CD147) is the target for organomercurial inhibition of monocarboxylate transporter isoforms 1 and 4; the ancillary protein for the insensitive MCT2 is EMBIGIN (gp70). J Biol Chem 280:27213–27221

    Article  CAS  PubMed  Google Scholar 

  34. Iacono KT, Brown AL, Greene MI, Saouaf SJ (2007) CD147 immunoglobulin superfamily receptor function and role in pathology. Exp Molec Pathol 83:283–295

    Article  CAS  Google Scholar 

  35. Braundmeier AG, Fazleabas AT, Lessey BA, Guo H, Toole BP, Nowaak RA (2006) Extracellular matrix metalloproteinase inducer regulates metalloproteinases in human uterine endometrium. J Clin Endocrinol Metab 91:2358–2365

    Article  CAS  PubMed  Google Scholar 

  36. Mossop H, Linhares IM, Zhou X, Bongiovanni AM, Forney L, Ledger WJ, Witkin SS (2012) Effect of lactic acid on vaginal EMMPRIN production: implications for altered vaginal microbiota-related pathology. Reprod Sci 19Suppl:395A

    Google Scholar 

  37. Braundmeier AG, Dayger CA, Mehrotra P, Belton RJ Jr, Nowak RA (2012) EMMPRIN is secreted by human uterine epithelial cells in microvescicles and stimulates metalloproteinase production by human uterine fibroblast cells. Reprod Sci 19:1292–1301

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no conflict of interest. The authors have full control of all primary data and agree to allow the journal to review their data if requested.

Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Botucatu Medical School, São Paulo State University, Botucatu, São Paulo, SP, Brazil

    Mariana Romão & Ingrid Cristina Weel

  2. Division of Immunology and Infectious Diseases, Department of Obstetrics and Gynecology, Weill Cornell Medical College, 525 East 68th Street, Box 35, New York, NY, 10065, USA

    Shirlee Jaffe Lifshitz & Steven S. Witkin

  3. Department of Microbiology and Immunology, Institute of Biosciences, São Paulo State University, Botucatu, SP, Brazil

    Maria Terezinha Serrão Peraçoli

Authors
  1. Mariana Romão
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ingrid Cristina Weel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shirlee Jaffe Lifshitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Terezinha Serrão Peraçoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Steven S. Witkin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steven S. Witkin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Romão, M., Weel, I.C., Lifshitz, S.J. et al. Elevated hyaluronan and extracellular matrix metalloproteinase inducer levels in women with preeclampsia. Arch Gynecol Obstet 289, 575–579 (2014). https://doi.org/10.1007/s00404-013-3021-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-013-3021-7

Keywords

Search

Navigation