Skip to main content

Advertisement

SpringerLink
Log in

Are we getting closer to a Nobel Prize for unraveling preeclampsia?

  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Preeclampsia is the major cause of maternal and fetal morbidity and mortality, involving 15% to 20% of pregnancies in developed countries and even more in less developed parts of the world. Superficial placentation driven by immune maladaptation, with subsequently reduced concentrations of angiogenic growth factors and increased placental debris in the maternal circulation, are likely responsible. Recent advances suggest that antiangiogenic factors (soluble fms-like tyrosine receptor kinase and soluble endoglin), altered relaxin-mediated mechanisms leading to impaired nitric oxide production through asymmetrical dimethylarginine production, and activating antibodies directed at the angiotensin II type 1 receptor may be responsible. The field of preeclampsia research is enjoying a well-deserved blossoming of novel ideas and approaches. We hope the activity will lead to much earlier diagnostic capacities and novel prophylactic treatments. The prize will go to the affected women and their afflicted children. For the investigators in the area, such a prize would be welcome.

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 and Recommended Reading

  1. Sibai B, Dekker G, Kupferminc M: Pre-eclampsia. Lancet 2005, 365:785–799.

    PubMed  Google Scholar 

  2. Poston L, Briley AL, Seed PT, et al.: Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Vitamins in Pre-eclampsia (VIP) Trial Consortium. Lancet 2006, 367:1145–1154.

    Article  PubMed  CAS  Google Scholar 

  3. Askie LM, Duley L, Henderson-Smart DJ, Stewart LA: Antiplatelet agents for prevention of pre-eclampsia: a meta-analysis of individual patient data. PARIS Collaborative Group. Lancet 2007, 369:1791–1798.

    Article  PubMed  CAS  Google Scholar 

  4. Altman D, Carroli G, Duley L, et al.: Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Magpie Trial Collaboration Group. Lancet 2002, 359:1877–1890.

    Article  PubMed  Google Scholar 

  5. Maynard SE, Min JY, Merchan J, et al.: Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 2003, 111:649–658.

    PubMed  CAS  Google Scholar 

  6. Levine RJ, Maynard SE, Qian C, et al.: Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004, 350:672–683.

    Article  PubMed  CAS  Google Scholar 

  7. Levine RJ, Thadhani R, Qian C, et al.: Urinary placental growth factor and risk of preeclampsia. JAMA 2005, 293:77–85.

    Article  PubMed  CAS  Google Scholar 

  8. Venkatesha S, Toporsian M, Lam C, et al.: Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med 2006, 12:642–649.

    Article  PubMed  CAS  Google Scholar 

  9. Levine RJ, Lam C, Qian C, et al.: Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. CPEP Study Group. N Engl J Med 2006, 355:992–1005.

    Article  PubMed  CAS  Google Scholar 

  10. Verheul HM, Pinedo HM: Possible molecular mechanisms involved in the toxicity of angiogenesis inhibition. Nat Rev Cancer 2007, 7:475–485.

    Article  PubMed  CAS  Google Scholar 

  11. Eremina V, Jefferson JA, Kowalewska J, et al.: VEGF inhibition and renal thrombotic microangiopathy. N Engl J Med 2008, 358:1129–1136.

    Article  PubMed  CAS  Google Scholar 

  12. Chapman AB, Abraham WT, Zamudio S, et al.: Temporal relationships between hormonal and hemodynamic changes in early human pregnancy. Kidney Int 1998, 54:2056–2063.

    Article  PubMed  CAS  Google Scholar 

  13. Groenendijk R, Trimbos JB, Wallenburg HC: Hemodynamic measurements in preeclampsia: preliminary observations. Am J Obstet Gynecol 1984, 150:232–236.

    PubMed  CAS  Google Scholar 

  14. Ma S, Gundlach AL: Relaxin-family peptide and receptor systems in brain: insights from recent anatomical and functional studies. Adv Exp Med Biol 2007, 612:119–137.

    Article  PubMed  Google Scholar 

  15. Jeyabalan A, Shroff SG, Novak J, Conrad KP: The vascular actions of relaxin. Adv Exp Med Biol 2007, 612:65–87.

    Article  PubMed  Google Scholar 

  16. Novak J, Danielson LA, Kerchner LJ, et al.: Relaxin is essential for renal vasodilation during pregnancy in conscious rats. J Clin Invest 2001, 107:1469–1475.

    Article  PubMed  CAS  Google Scholar 

  17. Jeyabalan A, Novak J, Danielson LA, et al.: Essential role for vascular gelatinase activity in relaxin-induced renal vasodilation, hyperfiltration, and reduced myogenic reactivity of small arteries. Circ Res 2003, 93:1249–1257.

    Article  PubMed  CAS  Google Scholar 

  18. Carbillon L, Uzan M, Uzan S: Pregnancy, vascular tone, and maternal hemodynamics: a crucial adaptation. Obstet Gynecol Surv 2000, 55:574–581.

    Article  PubMed  CAS  Google Scholar 

  19. Savvidou MD, Hingorani AD, Tsikas D, et al.: Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia. Lancet 2003, 361:1511–1517.

    Article  PubMed  CAS  Google Scholar 

  20. Wallukat G, Homuth V, Fischer T, et al.: Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest 1999, 103:945–952.

    Article  PubMed  CAS  Google Scholar 

  21. Fu ML, Herlitz H, Schulze W, et al.: Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension. J Hypertens 2000, 18:945–953.

    Article  PubMed  CAS  Google Scholar 

  22. Dechend R, Viedt C, Muller DN, et al.: AT1 receptor agonistic antibodies from preeclamptic patients stimulate NADPH oxidase. Circulation 2003, 107:1632–1639.

    Article  PubMed  CAS  Google Scholar 

  23. Bohlender J, Ganten D, Luft FC: Rats transgenic for human renin and human angiotensinogen as a model for gestational hypertension. J Am Soc Nephrol 2000, 11:2056–2061.

    PubMed  CAS  Google Scholar 

  24. Dechend R, Gratze P, Wallukat G, et al.: Agonistic autoantibodies to the AT1 receptor in a transgenic rat model of preeclampsia. Hypertension 2005, 45:742–746.

    Article  PubMed  CAS  Google Scholar 

  25. Xia Y, Wen H, Bobst S, et al.: Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human trophoblast cells. J Soc Gynecol Investig 2003, 10:82–93.

    Article  PubMed  CAS  Google Scholar 

  26. Thway TM, Shlykov SG, Day MC, et al.: Antibodies from preeclamptic patients stimulate increased intracellular Ca2+ mobilization through angiotensin receptor activation. Circulation 2004, 110:1612–1619.

    Article  PubMed  CAS  Google Scholar 

  27. Bobst SM, Day MC, Gilstrap LC 3rd, et al.: Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human mesangial cells and induce interleukin-6 and plasminogen activator inhibitor-1 secretion. Am J Hypertens 2005, 18:330–336.

    Article  PubMed  CAS  Google Scholar 

  28. Zhou CC, Ahmad S, Mi T, et al.: Angiotensin II induces soluble fms-like tyrosine kinase-1 release via calcineurin signaling pathway in pregnancy. Circ Res 2007, 100:88–95.

    Article  PubMed  CAS  Google Scholar 

  29. Zhou CC, Ahmad S, Mi T, et al.: Autoantibody from women with preeclampsia induces soluble Fms-like tyrosine kinase-1 production via angiotensin type 1 receptor and calcineurin/nuclear factor of activated T-cells signaling. Hypertension 2008, 51:991–992.

    Article  Google Scholar 

  30. Hubel CA, Wallukat G, Wolf M, et al.: Agonistic angiotensin II type 1 receptor autoantibodies in postpartum women with a history of preeclampsia. Hypertension 2007, 49:612–617.

    Article  PubMed  CAS  Google Scholar 

  31. Herse F, Dechend R, Harsem NK, et al.: Dysregulation of the circulating and tissue-based renin-angiotensin system in preeclampsia. Hypertension 2007, 49:604–611.

    Article  PubMed  CAS  Google Scholar 

  32. Walther T, Wallukat G, Jank A, et al.: Angiotensin II type 1 receptor agonistic antibodies reflect fundamental alterations in the uteroplacental vasculature. Hypertension 2005, 46:1275–1279.

    Article  PubMed  CAS  Google Scholar 

  33. Stepan H, Faber R, Wessel N, et al.: Relation between circulating angiotensin II type 1 receptor agonistic autoantibodies and soluble fms-like tyrosine kinase 1 in the pathogenesis of preeclampsia. J Clin Endocrinol Metab 2006, 91:2424–2427.

    Article  PubMed  CAS  Google Scholar 

  34. Stepan H, Wallukat G, Schultheiss HP, et al.: Is parvovirus B19 the cause for autoimmunity against the angiotensin II type receptor? J Reprod Immunol 2007, 73:130–134.

    Article  PubMed  CAS  Google Scholar 

  35. Dragun D, Muller DN, Brasen JH, et al.: Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection. N Engl J Med 2005, 352:558–569.

    Article  PubMed  CAS  Google Scholar 

  36. Zhou CC, Zhang Y, Irani RA, et al.: Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice. Nat Med 2008, 14:855–862.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Max-Delbrück Center for Molecular Medicine, Building 84, Robert-Rössle-Strasse 10, 13125, Berlin, Germany

    Friedrich C. Luft

Authors
  1. Ralf Dechend
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Friedrich C. Luft
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Friedrich C. Luft.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dechend, R., Luft, F.C. Are we getting closer to a Nobel Prize for unraveling preeclampsia?. Curr Cardiol Rep 10, 440–447 (2008). https://doi.org/10.1007/s11886-008-0070-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11886-008-0070-9

Keywords

Search

Navigation