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Was Morbus Osler und Präeklampsie (nicht) gemeinsam haben

  • Angela Köninger
  • Buu-Phuc Nguyen
  • Alexandra Gellhaus
  • Freya Dröge
  • Rainer Kimmig
  • Urban Geisthoff
Gynäkologie aktuell
  • 22 Downloads

Zusammenfassung

Das Rendu-Osler-Weber-Syndrom Typ 1 (hereditäre hämorrhagische Teleangiektasie 1, HHT1) und die Präeklampsie basieren beide auf einer pathologischen Funktion des Endoglins. Patienten mit HHT1 haben einen heterozygoten Endoglingendefekt, der zu einer systemischen vaskulären Dysplasie führt. Bei der Präeklampsie produziert der Trophoblast lösliches Endoglin (sEng). sEng wirkt wie ein „Antikörper“, der das mütterliche Endoglinrezeptorsubstrat hemmt und antagonisiert. Dies führt zu einer endothelialen Dysfunktion. Im Beitrag werden 2 verschiedene endoglinbedingte Erkrankungen miteinander verglichen, um eine fundiertere Einsicht in die spezifischen klinischen Merkmale zu gewinnen. Diskutiert werden ferner Managementoptionen für schwangere Patientinnen mit HHT.

Schlüsselwörter

Schwangerschaft Endoglin Präeklampsie Hereditäre hämorrhagische Teleangiektasie Plazentare Dysfunktion 

What Osler–Weber–Rendu disease and pre-eclampsia do (not) have in common

Abstract

Rendu–Osler–Weber syndrome type 1 (hereditary hemorrhagic telangiectasia 1, HHT 1) and pre-eclampsia both base on a pathological function of endoglin. Patients with HHT 1 have a heterozygous endoglin gene defect, resulting in systemic vascular dysplasia. In pre-eclampsia, trophoblast produces soluble endoglin (sEng). sEng acts like an “antibody” which inhibits and antagonizes the maternal endoglin-receptor substrate, resulting in endothelial dysfunction. In this article, two different endoglin-related disorders are compared with each other with the aim to provide more insight into the specific clinical features. Additionally, management options for pregnant patients with HHT are discussed.

Keywords

Pregnancy Endoglin Placental dysfunction Telangiectasia, hereditary hemorrhagic Preeclampsia 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt

A. Köninger, B.-P. Nguyen, A. Gellhaus, F. Dröge, R. Kimmig und U. Geisthoff geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Bari O, Cohen PR (2017) Hereditary hemorrhagic telangiectasia and pregnancy: potential adverse events and pregnancy outcomes. Int J Womens Health 9:373–378.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Braverman IM, Keh A, Jacobson BS (1990) Ultrastructure and three-dimensional organization of the telangiectases of hereditary hemorrhagic telangiectasia. J Invest Dermatol 95:422–427.CrossRefGoogle Scholar
  3. 3.
    Castonguay R, Werner ED, Matthews RG, Presman E, Mulivor AW, Solban N, Sako D, Pearsall RS, Underwood KW, Seehra J, Kumar R, Grinberg AV (2011) Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its orphan domain, inhibits blood vessel formation, and suppresses tumor growth. J Biol Chem 286:30034–30046.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Clark DE, Smith SK, He Y, Day KA, Licence DR, Corps AN, Lammoglia R, Charnock-Jones DS (1998) A vascular endothelial growth factor antagonist is produced by the human placenta and released into the maternal circulation. Biol Reprod 59:1540–1548.CrossRefGoogle Scholar
  5. 5.
    van Cutsem E, Rutgeerts P, Vantrappen G (1990) Treatment of bleeding gastrointestinal vascular malformations with oestrogen-progesterone. Lancet 335:953–955.CrossRefGoogle Scholar
  6. 6.
    Eli I, Gamboa NT, Joyce EJ, Park MS, Taussky P, Schmidt RH, Couldwell WT, McDonald J, Whitehead KJ, Kalani MYS (2018) Clinical presentation and treatment paradigms in patients with hereditary hemorrhagic telangiectasia and spinal vascular malformations. J Clin Neurosci 50:51–57.CrossRefPubMedGoogle Scholar
  7. 7.
    Faughnan ME, Granton JT, Young LH (2009) The pulmonary vascular complications of hereditary haemorrhagic telangiectasia. Eur Respir J 33:1186–1194.CrossRefPubMedGoogle Scholar
  8. 8.
    Geisthoff UW, Seyfert UT, Kübler M, Bieg B, Plinkert PK, König J (2014) Treatment of epistaxis in hereditary hemorrhagic telangiectasia with tranexamic acid—a double-blind placebo-controlled cross-over phase IIIB study. Thromb Res 134:565–571.CrossRefPubMedGoogle Scholar
  9. 9.
    Gougos A, Letarte M (1990) Primary structure of endoglin, an RGD-containing glycoprotein of human endothelial cells. J Biol Chem 265:8361–8364.PubMedGoogle Scholar
  10. 10.
    de Gussem EM, Lausman AY, Beder AJ, Edwards CP, Blanker MH, Terbrugge KG, Mager JJ, Faughnan ME (2014) Outcomes of pregnancy in women with hereditary hemorrhagic telangiectasia. Obstet Gynecol 123:514–520.CrossRefPubMedGoogle Scholar
  11. 11.
    Jameson JJ, Cave DR (2004) Hormonal and antihormonal therapy for epistaxis in hereditary hemorrhagic telangiectasia. Laryngoscope 114:705–709.CrossRefPubMedGoogle Scholar
  12. 12.
    Jerkic M, Rivas-Elena JV, Prieto M, Carrón R, Sanz-Rodríguez F, Pérez-Barriocanal F, Rodríguez-Barbero A, Bernabéu C, López-Novoa JM (2004) Endoglin regulates nitric oxide-dependent vasodilatation. Faseb J 18:609–611.CrossRefPubMedGoogle Scholar
  13. 13.
    Karumanchi SA (2016) Angiogenic factors in preeclampsia: from diagnosis to therapy. Hypertension 67:1072–1079.CrossRefPubMedGoogle Scholar
  14. 14.
    Kendall RL, Thomas KA (1993) Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci USA 90:10705–10709.CrossRefGoogle Scholar
  15. 15.
    Khalid S, Garcia-Tsao G (2008) Hepatic vascular malformations in hereditary hemorrhagic Telangiectasia. Semin Liver Dis 28:247–258.CrossRefPubMedGoogle Scholar
  16. 16.
    Lebrin F, Srun S, Raymond K, Martin S, van den Brink S, Freitas C, Bréant C, Mathivet T, Larrivée B, Thomas J‑L, Arthur HM, Westermann CJJ, Disch F, Mager JJ, Snijder RJ, Eichmann A, Mummery CL (2010) Thalidomide stimulates vessel maturation and reduces epistaxis in individuals with hereditary hemorrhagic telangiectasia. Nat Med 16:420–428.CrossRefPubMedGoogle Scholar
  17. 17.
    Letteboer TGW, Mager H‑J, Snijder RJ, Lindhout D, Ploos van Amstel H‑K, Zanen P, Westermann KJJ (2008) Genotype-phenotype relationship for localization and age distribution of telangiectases in hereditary hemorrhagic telangiectasia. Am J Med Genet A 146 A:2733–2739.CrossRefPubMedGoogle Scholar
  18. 18.
    Li C, Hampson IN, Hampson L, Kumar P, Bernabeu C, Kumar S (2000) CD105 antagonizes the inhibitory signaling of transforming growth factor beta1 on human vascular endothelial cells. FASEB J 14:55–64.CrossRefGoogle Scholar
  19. 19.
    Li C, Issa R, Kumar P, Hampson IN, Lopez-Novoa JM, Bernabeu C, Kumar S (2003) CD105 prevents apoptosis in hypoxic endothelial cells. J Cell Sci 116:2677–2685.CrossRefPubMedGoogle Scholar
  20. 20.
    Li DY, Sorensen LK, Brooke BS, Urness LD, Davis EC, Taylor DG, Boak BB, Wendel DP (1999) Defective angiogenesis in mice lacking endoglin. Science 284:1534–1537.CrossRefGoogle Scholar
  21. 21.
    Maynard SE, Min J‑Y, Merchan J, Lim K‑H, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, Epstein FH, Sukhatme VP, Karumanchi SA (2003) Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest 111:649–658.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    McAllister KA, Grogg KM, Johnson DW, Gallione CJ, Baldwin MA, Jackson CE, Helmbold EA, Markel DS, McKinnon WC, Murrel J, McCormick MK, Pericak-Vance MA, Heutink P, Oostra BA, Haitjema T, Westerman CJJ, Porteous ME, Guttmacher AE, Letarte M, Marchuk DA (1994) Endoglin, a TGF-β binding protein of endothelial cells, is the gene for hereditary haemorrhagic telangiectasia type 1. Nat Genet 8:345–351.CrossRefPubMedGoogle Scholar
  23. 23.
    Monsivais D, Matzuk MM, Pangas SA (2017) The TGF-β family in the reproductive tract. Cold Spring Harb Perspect Biol 9:a22251.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Mowers KL, Sekarski L, White AJ, Grady RM (2018) Pulmonary arteriovenous malformations in children with hereditary hemorrhagic telangiectasia: a longitudinal study. Pulm Circ 8:204589401878669.CrossRefGoogle Scholar
  25. 25.
    Plauchu H, de Chadarévian JP, Bideau A, Robert JM (1989) Age-related clinical profile of hereditary hemorrhagic telangiectasia in an epidemiologically recruited population. Am J Med Genet 32:291–297.CrossRefPubMedGoogle Scholar
  26. 26.
    Powe CE, Levine RJ, Karumanchi SA (2011) Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease. Circulation 123:2856–2869.CrossRefPubMedGoogle Scholar
  27. 27.
    Redman CW, Sargent IL (2005) Latest advances in understanding preeclampsia. Science 308:1592–1594.CrossRefPubMedGoogle Scholar
  28. 28.
    Reilly PJ, Nostrant TT (1984) Clinical manifestations of hereditary hemorrhagic telangiectasia. Am J Gastroenterol 79:363–367.PubMedGoogle Scholar
  29. 29.
    Riss D, Burian M, Wolf A, Kranebitter V, Kaider A, Arnoldner C (2015) Intranasal submucosal bevacizumab for epistaxis in hereditary hemorrhagic telangiectasia: a double-blind, randomized, placebo-controlled trial. Head Neck 37:783–787.CrossRefPubMedGoogle Scholar
  30. 30.
    Rossi E, Smadja DM, Boscolo E, Langa C, Arevalo MA, Pericacho M, Gamella-Pozuelo L, Kauskot A, Botella LM, Gaussem P, Bischoff J, Lopez-Novoa JM, Bernabeu C (2016) Endoglin regulates mural cell adhesion in the circulatory system. Cell Mol Life Sci 73:1715–1739.CrossRefPubMedGoogle Scholar
  31. 31.
    Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, Kjeldsen AD, Plauchu H (2000) Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Genet 91:66–67.CrossRefGoogle Scholar
  32. 32.
    Shovlin CL, Sodhi V, McCarthy A, Lasjaunias P, Jackson JE, Sheppard MN (2008) Estimates of maternal risks of pregnancy for women with hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): suggested approach for obstetric services. BJOG 115:1108–1115.CrossRefPubMedGoogle Scholar
  33. 33.
    Signore C, Mills JL, Qian C, Yu KF, Rana S, Karumanchi SA, Levine RJ (2008) Circulating soluble endoglin and placental abruption. Prenat Diagn 28:852–858.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Toporsian M, Gros R, Kabir MG, Vera S, Govindaraju K, Eidelman DH, Husain M, Letarte M (2005) A role for endoglin in coupling eNOS activity and regulating vascular tone revealed in hereditary hemorrhagic telangiectasia. Circ Res 96:684–692.CrossRefPubMedGoogle Scholar
  35. 35.
    Torsney E, Charlton R, Parums D, Collis M, Arthur HM (2002) Inducible expression of human endoglin during inflammation and wound healing in vivo. Inflamm Res 51:464–470.CrossRefGoogle Scholar
  36. 36.
    Venkatesha S, Toporsian M, Lam C, Hanai J, Mammoto T, Kim YM, Bdolah Y, Lim K‑H, Yuan H‑T, Libermann TA, Stillman IE, Roberts D, D’Amore PA, Epstein FH, Sellke FW, Romero R, Sukhatme VP, Letarte M, Karumanchi SA (2006) Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med 12:642–649.CrossRefPubMedGoogle Scholar
  37. 37.
    Wain K, Swanson K, Watson W, Jeavons E, Weaver A, Lindor N (2012) Hereditary hemorrhagic telangiectasia and risks for adverse pregnancy outcomes. Am J Med Genet A 158:2009–2014.CrossRefGoogle Scholar
  38. 38.
    HHT Foundation International. Understanding HHT (2018) http://www.curehht.org. http://www.curehht.org. Letzte Aktualisierung: 2018
  39. 39.
    Mutation Database. ARUP Laboratories, University of Utah, Department of Pathology (2006-2018). http://www.arup.utha.edu/database/hht/. Letzte Aktualisierung: 1/2013 (Endoglin database) und 1/2018 (ACVRL1 database)

Copyright information

© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2018

Authors and Affiliations

  • Angela Köninger
    • 1
  • Buu-Phuc Nguyen
    • 1
  • Alexandra Gellhaus
    • 1
  • Freya Dröge
    • 2
  • Rainer Kimmig
    • 1
  • Urban Geisthoff
    • 3
  1. 1.Klinik für Frauenheilkunde und GeburtshilfeUniversitätsklinikum EssenEssenDeutschland
  2. 2.Klinik für Hals-Nasen-Ohren-HeilkundeUniversitätsklinikum EssenEssenDeutschland
  3. 3.Klinik für Hals-Nasen-Ohren-HeilkundeUniversitätsklinikum Marburg, Philipps Universität MarburgMarburgDeutschland

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