Skip to main content

Advertisement

SpringerLink
Log in

A potential pathophysiological role for galectins and the renin–angiotensin system in preeclampsia

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

This review discusses a potential role of galectins and the renin–angiotensin system (RAS) in the pathophysiology of preeclampsia (PE). Preeclampsia affects between 3 and 5 % of all pregnancies and is a heterogeneous disease, which may be caused by multiple factors. The only cure is the delivery of the placenta, which may result in a premature delivery and baby. Probably due to its heterogeneity, PE studies in human have hitherto only led to the identification of a limited number of factors involved in the pathogenesis of the disease. Animal models, particularly in mice and rats, have been used to gain further insight into the molecular pathology behind PE. In this review, we discuss the picture emerging from human and animal studies pointing to galectins and the RAS being associated with the PE syndrome and affecting a broad range of cellular signaling components. Moreover, we review the epidemiological evidence for PE increasing the risk of future cardiovascular disease later in life.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Redman CW, Sargent IL (2005) Latest advances in understanding preeclampsia. Science 308(5728):1592–1594. doi:10.1126/science.1111726

    CAS  PubMed  Google Scholar 

  2. Duley L (2009) The global impact of pre-eclampsia and eclampsia. Semin Perinatol 33(3):130–137. doi:10.1053/j.semperi.2009.02.010

    PubMed  Google Scholar 

  3. Redman CW, Sargent IL (2010) Immunology of pre-eclampsia. Am J Reprod Immunol 63(6):534–543. doi:10.1111/j.1600-0897.2010.00831.x

    CAS  PubMed  Google Scholar 

  4. Staff AC, Benton SJ, von Dadelszen P, Roberts JM, Taylor RN, Powers RW, Charnock-Jones DS, Redman CW (2013) Redefining preeclampsia using placenta-derived biomarkers. Hypertension 61(5):932–942. doi:10.1161/HYPERTENSIONAHA.111.00250

    CAS  PubMed  Google Scholar 

  5. Staff AC, Johnsen GM, Dechend R, Redman CW (2014) Preeclampsia and uteroplacental acute atherosis: immune and inflammatory factors. J Reprod Immunol 101–102:120–126. doi:10.1016/j.jri.2013.09.001

    PubMed  Google Scholar 

  6. Stevens DU, Al-Nasiry S, Bulten J, Spaanderman ME (2013) Decidual vasculopathy in preeclampsia: lesion characteristics relate to disease severity and perinatal outcome. Placenta 34(9):805–809. doi:10.1016/j.placenta.2013.05.008

    CAS  PubMed  Google Scholar 

  7. Burton GJ, Woods AW, Jauniaux E, Kingdom JC (2009) Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta 30(6):473–482. doi:10.1016/j.placenta.2009.02.009

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Staff AC, Dechend R, Pijnenborg R (2010) Learning from the placenta: acute atherosis and vascular remodeling in preeclampsia—novel aspects for atherosclerosis and future cardiovascular health. Hypertension 56(6):1026–1034. doi:10.1161/HYPERTENSIONAHA.110.157743

    CAS  PubMed  Google Scholar 

  9. Redman CW, Sargent IL, Staff AC (2014) IFPA Senior Award Lecture: making sense of pre-eclampsia—two placental causes of preeclampsia? Placenta 35(Suppl):S20–25. doi:10.1016/j.placenta.2013.12.008

    PubMed  Google Scholar 

  10. Maynard SE, Min JY, Merchan J, Lim KH, 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(5):649–658. doi:10.1172/JCI17189

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Barondes SH, Castronovo V, Cooper DN, Cummings RD, Drickamer K, Feizi T, Gitt MA, Hirabayashi J, Hughes C, Kasai K et al (1994) Galectins: a family of animal beta-galactoside-binding lectins. Cell 76(4):597–598 pii:0092-8674(94)90498-7

    CAS  PubMed  Google Scholar 

  12. Liu FT, Patterson RJ, Wang JL (2002) Intracellular functions of galectins. Biochim Biophys Acta 1572(2–3):263–273

    CAS  PubMed  Google Scholar 

  13. Hernandez JD, Baum LG (2002) Ah, sweet mystery of death! Galectins and control of cell fate. Glycobiology 12(10):127R–136R

    CAS  PubMed  Google Scholar 

  14. Nickel W (2005) Unconventional secretory routes: direct protein export across the plasma membrane of mammalian cells. Traffic 6(8):607–614 (Copenhagen, Denmark)

    CAS  PubMed  Google Scholar 

  15. Rabinovich GA, Liu FT, Hirashima M, Anderson A (2007) An emerging role for galectins in tuning the immune response: lessons from experimental models of inflammatory disease, autoimmunity and cancer. Scand J Immunol 66(2–3):143–158

    CAS  PubMed  Google Scholar 

  16. Hirabayashi J, Ayaki H, Soma G, Kasai K (1989) Cloning and nucleotide sequence of a full-length cDNA for human 14 kDa beta-galactoside-binding lectin. Biochim Biophys Acta 1008(1):85–91

    CAS  PubMed  Google Scholar 

  17. Camby I, Le Mercier M, Lefranc F, Kiss R (2006) Galectin-1: a small protein with major functions. Glycobiology 16(11):137R–157R

    CAS  PubMed  Google Scholar 

  18. Stillman BN, Hsu DK, Pang M, Brewer CF, Johnson P, Liu FT, Baum LG (2006) Galectin-3 and galectin-1 bind distinct cell surface glycoprotein receptors to induce T cell death. J Immunol 176(2):778–789

    CAS  PubMed  Google Scholar 

  19. Blaser C, Kaufmann M, Muller C, Zimmermann C, Wells V, Mallucci L, Pircher H (1998) Beta-galactoside-binding protein secreted by activated T cells inhibits antigen-induced proliferation of T cells. Eur J Immunol 28(8):2311–2319

    CAS  PubMed  Google Scholar 

  20. Motran CC, Molinder KM, Liu SD, Poirier F, Miceli MC (2008) Galectin-1 functions as a Th2 cytokine that selectively induces Th1 apoptosis and promotes Th2 function. Eur J Immunol 38(11):3015–3027

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Blois SM, Ilarregui JM, Tometten M, Garcia M, Orsal AS, Cordo-Russo R, Toscano MA, Bianco GA, Kobelt P, Handjiski B, Tirado I, Markert UR, Klapp BF, Poirier F, Szekeres-Bartho J, Rabinovich GA, Arck PC (2007) A pivotal role for galectin-1 in fetomaternal tolerance. Nat Med 13(12):1450–1457

    CAS  PubMed  Google Scholar 

  22. Tirado-Gonzalez I, Freitag N, Barrientos G, Shaikly V, Nagaeva O, Strand M, Kjellberg L, Klapp BF, Mincheva-Nilsson L, Cohen M, Blois SM (2013) Galectin-1 influences trophoblast immune evasion and emerges as a predictive factor for the outcome of pregnancy. Mol Hum Reprod 19(1):43–53

    CAS  PubMed  Google Scholar 

  23. Choe YS, Shim C, Choi D, Lee CS, Lee KK, Kim K (1997) Expression of galectin-1 mRNA in the mouse uterus is under the control of ovarian steroids during blastocyst implantation. Mol Reprod Dev 48(2):261–266

    CAS  PubMed  Google Scholar 

  24. von Wolff M, Wang X, Gabius HJ, Strowitzki T (2005) Galectin fingerprinting in human endometrium and decidua during the menstrual cycle and in early gestation. Mol Hum Reprod 11(3):189–194

    Google Scholar 

  25. Barrientos G, Freitag N, Tirado-Gonzalez I, Unverdorben L, Jeschke U, Thijssen VL, Blois SM (2014) Involvement of galectin-1 in reproduction: past, present and future. Human Repro Update 20(2):175–193

    CAS  Google Scholar 

  26. Bevan BH, Kilpatrick DC, Liston WA, Hirabayashi J, Kasai K (1994) Immunohistochemical localization of a beta-D-galactoside-binding lectin at the human maternofetal interface. Histochem J 26(7):582–586

    CAS  PubMed  Google Scholar 

  27. Fischer I, Redel S, Hofmann S, Kuhn C, Friese K, Walzel H, Jeschke U (2010) Stimulation of syncytium formation in vitro in human trophoblast cells by galectin-1. Placenta 31(9):825–832

    CAS  PubMed  Google Scholar 

  28. Kolundzic N, Bojić-Trbojević T, Kovaćević T, Stefanoska I, Kadoya T, Vićovac L (2011) Galectin-1 is part of human trophoblast invasion machinery: a functional study in vitro. PloS One 6(12):e28514

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Aplin JD (1991) Implantation, trophoblast differentiation and haemochorial placentation: mechanistic evidence in vivo and in vitro. J Cell Sci 99(Pt 4):681–692

    PubMed  Google Scholar 

  30. Hunt JS, Petroff MG, McIntire RH, Ober C (2005) HLA-G and immune tolerance in pregnancy. Faseb J 19(7):681–693

    CAS  PubMed  Google Scholar 

  31. Thijssen VL, Barkan B, Shoji H, Aries IM, Mathieu V, Deltour L, Hackeng TM, Kiss R, Kloog Y, Poirier F, Griffioen AW (2010) Tumor cells secrete galectin-1 to enhance endothelial cell activity. Cancer Res 70(15):6216–6224

    CAS  PubMed  Google Scholar 

  32. Hsieh SH, Ying NW, Wu MH, Chiang WF, Hsu CL, Wong TY, Jin YT, Hong TM, Chen YL (2008) Galectin-1, a novel ligand of neuropilin-1, activates VEGFR-2 signaling and modulates the migration of vascular endothelial cells. Oncogene 27(26):3746–3753

    CAS  PubMed  Google Scholar 

  33. Douglas NC, Tang H, Gomez R, Pytowski B, Hicklin DJ, Sauer CM, Kitajewski J, Sauer MV, Zimmermann RC (2009) Vascular endothelial growth factor receptor 2 (VEGFR-2) functions to promote uterine decidual angiogenesis during early pregnancy in the mouse. Endocrinology 150(8):3845–3854

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Halder JB, Zhao X, Soker S, Paria BC, Klagsbrun M, Das SK, Dey SK (2000) Differential expression of VEGF isoforms and VEGF(164)-specific receptor neuropilin-1 in the mouse uterus suggests a role for VEGF(164) in vascular permeability and angiogenesis during implantation. Genesis 26(3):213–224

    CAS  PubMed  Google Scholar 

  35. Plaks V, Birnberg T, Berkutzki T, Sela S, BenYashar A, Kalchenko V, Mor G, Keshet E, Dekel N, Neeman M, Jung S (2008) Uterine DCs are crucial for decidua formation during embryo implantation in mice. J Clin Investig 118(12):3954–3965

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Freitag N, Tirado-Gonzalez I, Barrientos G, Herse F, Thijssen VL, Weedon-Fekjaer SM, Schulz H, Wallukat G, Klapp BF, Nevers T, Sharma S, Staff AC, Dechend R, Blois SM (2013) Interfering with Gal-1-mediated angiogenesis contributes to the pathogenesis of preeclampsia. Proc Natl Acad Sci USA 110(28):11451–11456

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Jeschke U, Mayr D, Schiessl B, Mylonas I, Schulze S, Kuhn C, Friese K, Walzel H (2007) Expression of galectin-1, -3 (gal-1, gal-3) and the Thomsen–Friedenreich (TF) antigen in normal, IUGR, preeclamptic and HELLP placentas. Placenta 28(11–12):1165–1173

    CAS  PubMed  Google Scholar 

  38. Than NG, Erez O, Wildman DE, Tarca AL, Edwin SS, Abbas A, Hotra J, Kusanovic JP, Gotsch F, Hassan SS, Espinoza J, Papp Z, Romero R (2008) Severe preeclampsia is characterized by increased placental expression of galectin-1. J Matern Fetal Neonatal Med 21(7):429–442

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Molvarec A, Blois SM, Stenczer B, Toldi G, Tirado-Gonzalez I, Ito M, Shima T, Yoneda S, Vasarhelyi B, Rigo J Jr, Saito S (2011) Peripheral blood galectin-1-expressing T and natural killer cells in normal pregnancy and preeclampsia. Clinical Immunol 139(1):48–56 (Orlando, Fla)

    CAS  Google Scholar 

  40. Brewer CF, Miceli MC, Baum LG (2002) Clusters, bundles, arrays and lattices: novel mechanisms for lectin–saccharide-mediated cellular interactions. Curr Opin Struct Biol 12(5):616–623

    CAS  PubMed  Google Scholar 

  41. Vicovac L, Jankovic M, Cuperlovic M (1998) Galectin-1 and -3 in cells of the first trimester placental bed. Human Repro (Oxford, England) 13(3):730–735

    CAS  Google Scholar 

  42. Chen HY, Liu FT, Yang RY (2005) Roles of galectin-3 in immune responses. Archivum Immunologiae et Therapiae Experimentalis 53(6):497–504

    CAS  PubMed  Google Scholar 

  43. Alves CM, Silva DA, Azzolini AE, Marzocchi-Machado CM, Carvalho JV, Pajuaba AC, Lucisano-Valim YM, Chammas R, Liu FT, Roque-Barreira MC, Mineo JR (2010) Galectin-3 plays a modulatory role in the life span and activation of murine neutrophils during early Toxoplasma gondii infection. Immunobiology 215(6):475–485

    CAS  PubMed  Google Scholar 

  44. Iglesias MM, Rabinovich GA, Ambrosio AL, Castagna LF, Sotomayor CE, Wolfenstein-Todel C (1998) Purification of galectin-3 from ovine placenta: developmentally regulated expression and immunological relevance. Glycobiology 8(1):59–65

    CAS  PubMed  Google Scholar 

  45. Yang RY, Hsu DK, Liu FT (1996) Expression of galectin-3 modulates T-cell growth and apoptosis. Proc Natl Acad Sci USA 93(13):6737–6742

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Phillips B, Knisley K, Weitlauf KD, Dorsett J, Lee V, Weitlauf H (1996) Differential expression of two beta-galactoside-binding lectins in the reproductive tracts of pregnant mice. Biol Reprod 55(3):548–558

    CAS  PubMed  Google Scholar 

  47. Yang H, Lei C, Zhang W (2012) Expression of galectin-3 in mouse endometrium and its effect during embryo implantation. Repro Biomed Online 24(1):116–122

    CAS  Google Scholar 

  48. Maquoi E, van den Brule FA, Castronovo V, Foidart JM (1997) Changes in the distribution pattern of galectin-1 and galectin-3 in human placenta correlates with the differentiation pathways of trophoblasts. Placenta 18(5–6):433–439

    CAS  PubMed  Google Scholar 

  49. Lee VH, Lee AB, Phillips EB, Roberts JK, Weitlauf HM (1998) Spatio-temporal pattern for expression of galectin-3 in the murine utero-placental complex: evidence for differential regulation. Biol Reprod 58(5):1277–1282

    CAS  PubMed  Google Scholar 

  50. Crider-Pirkle S, Billingsley P, Faust C, Hardy DM, Lee V, Weitlauf H (2002) Cubilin, a binding partner for galectin-3 in the murine utero-placental complex. J Biol Chem 277(18):15904–15912

    CAS  PubMed  Google Scholar 

  51. Nangia-Makker P, Honjo Y, Sarvis R, Akahani S, Hogan V, Pienta KJ, Raz A (2000) Galectin-3 induces endothelial cell morphogenesis and angiogenesis. Am J Pathol 156(3):899–909

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Fukushi J, Makagiansar IT, Stallcup WB (2004) NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and alpha3beta1 integrin. Mol Biol Cell 15(8):3580–3590

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Wan SY, Zhang TF, Ding Y (2011) Galectin-3 enhances proliferation and angiogenesis of endothelial cells differentiated from bone marrow mesenchymal stem cells. Transpl Proc 43(10):3933–3938

    CAS  Google Scholar 

  54. Machado CM, Andrade LN, Teixeira VR, Costa FF, Melo CM, dos Santos SN, Nonogaki S, Liu FT, Bernardes ES, Camargo AA, Chammas R (2014) Galectin-3 disruption impaired tumoral angiogenesis by reducing VEGF secretion from TGFbeta1-induced macrophages. Cancer Med 3(2):201–214

    CAS  PubMed Central  PubMed  Google Scholar 

  55. Markowska AI, Jefferies KC, Panjwani N (2011) Galectin-3 protein modulates cell surface expression and activation of vascular endothelial growth factor receptor 2 in human endothelial cells. J Biol Chem 286(34):29913–29921

    CAS  PubMed Central  PubMed  Google Scholar 

  56. D’Haene N, Sauvage S, Maris C, Adanja I, Le Mercier M, Decaestecker C, Baum L, Salmon I (2013) VEGFR1 and VEGFR2 involvement in extracellular galectin-1- and galectin-3-induced angiogenesis. PLoS One 8(6):e67029

    PubMed Central  PubMed  Google Scholar 

  57. Than NG, Sumegi B, Than GN, Berente Z, Bohn H (1999) Isolation and sequence analysis of a cDNA encoding human placental tissue protein 13 (PP13), a new lysophospholipase, homologue of human eosinophil Charcot–Leyden Crystal protein. Placenta 20(8):703–710

    CAS  PubMed  Google Scholar 

  58. Than NG, Pick E, Bellyei S, Szigeti A, Burger O, Berente Z, Janaky T, Boronkai A, Kliman H, Meiri H, Bohn H, Than GN, Sumegi B (2004) Functional analyses of placental protein 13/galectin-13. Eur J Biochem/FEBS 271(6):1065–1078

    CAS  Google Scholar 

  59. Than NG, Romero R, Goodman M, Weckle A, Xing J, Dong Z, Xu Y, Tarquini F, Szilagyi A, Gal P, Hou Z, Tarca AL, Kim CJ, Kim JS, Haidarian S, Uddin M, Bohn H, Benirschke K, Santolaya-Forgas J, Grossman LI, Erez O, Hassan SS, Zavodszky P, Papp Z, Wildman DE (2009) A primate subfamily of galectins expressed at the maternal–fetal interface that promote immune cell death. Proc Natl Acad Sci USA 106(24):9731–9736

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Kliman HJ, Sammar M, Grimpel YI, Lynch SK, Milano KM, Pick E, Bejar J, Arad A, Lee JJ, Meiri H, Gonen R (2012) Placental protein 13 and decidual zones of necrosis: an immunologic diversion that may be linked to preeclampsia. Repro Sci 19(1):16–30 (Thousand Oaks, Calif)

    CAS  Google Scholar 

  61. Gizurarson S, Huppertz B, Osol G, Skarphedinsson JO, Mandala M, Meiri H (2013) Effects of placental protein 13 on the cardiovascular system in gravid and non-gravid rodents. Fetal Diagn Ther 33(4):257–264

    PubMed  Google Scholar 

  62. Than NG, Abdul Rahman O, Magenheim R, Nagy B, Fule T, Hargitai B, Sammar M, Hupuczi P, Tarca AL, Szabo G, Kovalszky I, Meiri H, Sziller I, Rigo J Jr, Romero R, Papp Z (2008) Placental protein 13 (galectin-13) has decreased placental expression but increased shedding and maternal serum concentrations in patients presenting with preterm pre-eclampsia and HELLP syndrome. Virchows Arch 453(4):387–400

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Ogawa M, Yanoma S, Nagashima Y, Okamoto N, Ishikawa H, Haruki A, Miyagi E, Takahashi T, Hirahara F, Miyagi Y (2007) Paradoxical discrepancy between the serum level and the placental intensity of PP5/TFPI-2 in preeclampsia and/or intrauterine growth restriction: possible interaction and correlation with glypican-3 hold the key. Placenta 28(2–3):224–232

    CAS  PubMed  Google Scholar 

  64. Sekizawa A, Purwosunu Y, Yoshimura S, Nakamura M, Shimizu H, Okai T, Rizzo N, Farina A (2009) PP13 mRNA expression in trophoblasts from preeclamptic placentas. Repro Sci Calif 16(4):408–413 (Thousand Oaks, Calif)

    CAS  Google Scholar 

  65. Huppertz B, Meiri H, Gizurarson S, Osol G, Sammar M (2013) Placental protein 13 (PP13): a new biological target shifting individualized risk assessment to personalized drug design combating pre-eclampsia. Human Repro Update 19(4):391–405

    CAS  Google Scholar 

  66. Nicolaides KH, Bindra R, Turan OM, Chefetz I, Sammar M, Meiri H, Tal J, Cuckle HS (2006) A novel approach to first-trimester screening for early pre-eclampsia combining serum PP-13 and Doppler ultrasound. Ultrasound Obstet Gynecol 27(1):13–17

    CAS  PubMed  Google Scholar 

  67. Wortelboer EJ, Koster MP, Cuckle HS, Stoutenbeek PH, Schielen PC, Visser GH (2010) First-trimester placental protein 13 and placental growth factor: markers for identification of women destined to develop early-onset pre-eclampsia. BJOG 117(11):1384–1389

    CAS  PubMed  Google Scholar 

  68. Ganten D, Minnich JL, Granger P, Hayduk K, Brecht HM, Barbeau A, Boucher R, Genest J (1971) Angiotensin-forming enzyme in brain tissue. Science 173(3991):64–65

    CAS  PubMed  Google Scholar 

  69. Weinberger MH, Kramer NJ, Grim CE, Petersen LP (1977) The effect of posture and saline loading on plasma renin activity and aldosterone concentration in pregnant, non-pregnant and estrogen-treated women. J Clin Endocrinol Metab 44(1):69–77. doi:10.1210/jcem-44-1-69

    CAS  PubMed  Google Scholar 

  70. Gordon RD, Parsons S, Symonds EM (1969) A prospective study of plasma-renin activity in normal and toxaemic pregnancy. Lancet 1(7590):347–349

    CAS  PubMed  Google Scholar 

  71. Herse F, Dechend R, Harsem NK, Wallukat G, Janke J, Qadri F, Hering L, Muller DN, Luft FC, Staff AC (2007) Dysregulation of the circulating and tissue-based renin–angiotensin system in preeclampsia. Hypertension 49(3):604–611. doi:10.1161/01.HYP.0000257797.49289.71

    CAS  PubMed  Google Scholar 

  72. Li C, Ansari R, Yu Z, Shah D (2000) Definitive molecular evidence of renin–angiotensin system in human uterine decidual cells. Hypertension 36(2):159–164

    CAS  PubMed  Google Scholar 

  73. Massani ZM, Sanguinetti R, Gallegos R, Raimondi D (1967) Angiotensin blood levels in normal and toxemic pregnancies. Am J Obstet Gynecol 99(3):313–317

    CAS  PubMed  Google Scholar 

  74. Gant NF, Daley GL, Chand S, Whalley PJ, MacDonald PC (1973) A study of angiotensin II pressor response throughout primigravid pregnancy. J Clin Invest 52(11):2682–2689. doi:10.1172/JCI107462

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Wallukat G, Homuth V, Fischer T, Lindschau C, Horstkamp B, Jupner A, Baur E, Nissen E, Vetter K, Neichel D, Dudenhausen JW, Haller H, Luft FC (1999) Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest 103(7):945–952. doi:10.1172/JCI4106

    CAS  PubMed Central  PubMed  Google Scholar 

  76. LaMarca B, Parrish M, Ray LF, Murphy SR, Roberts L, Glover P, Wallukat G, Wenzel K, Cockrell K, Martin JN Jr, Ryan MJ, Dechend R (2009) Hypertension in response to autoantibodies to the angiotensin II type I receptor (AT1-AA) in pregnant rats: role of endothelin-1. Hypertension 54(4):905–909. doi:10.1161/HYPERTENSIONAHA.109.137935

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Zhou CC, Zhang Y, Irani RA, Zhang H, Mi T, Popek EJ, Hicks MJ, Ramin SM, Kellems RE, Xia Y (2008) Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice. Nat Med 14(8):855–862. doi:10.1038/nm.1856

    CAS  PubMed Central  PubMed  Google Scholar 

  78. LaMarca B, Wallace K, Herse F, Wallukat G, Martin JN Jr, Weimer A, Dechend R (2011) Hypertension in response to placental ischemia during pregnancy: role of B lymphocytes. Hypertension 57(4):865–871. doi:10.1161/HYPERTENSIONAHA.110.167569

    CAS  PubMed Central  PubMed  Google Scholar 

  79. Novotny SR, Wallace K, Heath J, Moseley J, Dhillon P, Weimer A, Wallukat G, Herse F, Wenzel K, Martin JN Jr, Dechend R, Lamarca B (2012) Activating autoantibodies to the angiotensin II type I receptor play an important role in mediating hypertension in response to adoptive transfer of CD4+ T lymphocytes from placental ischemic rats. Am J Physiol Regul Integr Comp Physiol 302(10):R1197–1201. doi:10.1152/ajpregu.00623.2011

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Parikh SM, Karumanchi SA (2008) Putting pressure on pre-eclampsia. Nat Med 14(8):810–812. doi:10.1038/nm0808-810

    CAS  PubMed  Google Scholar 

  81. Dragun D, Muller DN, Brasen JH, Fritsche L, Nieminen-Kelha M, Dechend R, Kintscher U, Rudolph B, Hoebeke J, Eckert D, Mazak I, Plehm R, Schonemann C, Unger T, Budde K, Neumayer HH, Luft FC, Wallukat G (2005) Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection. N Engl J Med 352(6):558–569. doi:10.1056/NEJMoa035717

    CAS  PubMed  Google Scholar 

  82. Riemekasten G, Philippe A, Nather M, Slowinski T, Muller DN, Heidecke H, Matucci-Cerinic M, Czirjak L, Lukitsch I, Becker M, Kill A, van Laar JM, Catar R, Luft FC, Burmester GR, Hegner B, Dragun D (2011) Involvement of functional autoantibodies against vascular receptors in systemic sclerosis. Ann Rheum Dis 70(3):530–536. doi:10.1136/ard.2010.135772

    CAS  PubMed  Google Scholar 

  83. Giral M, Foucher Y, Dufay A, Van Huyen JP, Renaudin K, Moreau A, Philippe A, Hegner B, Dechend R, Heidecke H, Brouard S, Cesbron A, Castagnet S, Devys A, Soulillou JP, Dragun D (2013) Pretransplant sensitization against angiotensin II type 1 receptor is a risk factor for acute rejection and graft loss. Am J Transplant 13(10):2567–2576. doi:10.1111/ajt.12397

    CAS  PubMed  Google Scholar 

  84. Saxena AR, Karumanchi SA, Brown NJ, Royle CM, McElrath TF, Seely EW (2010) Increased sensitivity to angiotensin II is present postpartum in women with a history of hypertensive pregnancy. Hypertension 55(5):1239–1245. doi:10.1161/HYPERTENSIONAHA.109.147595

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Hladunewich MA, Kingdom J, Odutayo A, Burns K, Lai V, O’Brien T, Gandhi S, Zimpelmann J, Kiss A, Miller J, Cherney D (2011) Postpartum assessment of the renin angiotensin system in women with previous severe, early-onset preeclampsia. J Clin Endocrinol Metab 96(11):3517–3524. doi:10.1210/jc.2011-1125

    CAS  PubMed  Google Scholar 

  86. Kvehaugen AS, Melien O, Holmen OL, Laivuori H, Oian P, Andersgaard AB, Dechend R, Staff AC (2013) Single nucleotide polymorphisms in G protein signaling pathway genes in preeclampsia. Hypertension 61(3):655–661. doi:10.1161/HYPERTENSIONAHA.111.00331

    CAS  PubMed  Google Scholar 

  87. Wenzel K, Rajakumar A, Haase H, Geusens N, Hubner N, Schulz H, Brewer J, Roberts L, Hubel CA, Herse F, Hering L, Qadri F, Lindschau C, Wallukat G, Pijnenborg R, Heidecke H, Riemekasten G, Luft FC, Muller DN, Lamarca B, Dechend R (2011) Angiotensin II type 1 receptor antibodies and increased angiotensin II sensitivity in pregnant rats. Hypertension 58(1):77–84. doi:10.1161/HYPERTENSIONAHA.111.171348

    CAS  PubMed Central  PubMed  Google Scholar 

  88. AbdAlla S, Lother H, el Massiery A, Quitterer U (2001) Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat Med 7(9):1003–1009. doi:10.1038/nm0901-1003

    CAS  PubMed  Google Scholar 

  89. Zhou A, Carrell RW, Murphy MP, Wei Z, Yan Y, Stanley PL, Stein PE, Broughton Pipkin F, Read RJ (2010) A redox switch in angiotensinogen modulates angiotensin release. Nature 468(7320):108–111. doi:10.1038/nature09505

    CAS  PubMed Central  PubMed  Google Scholar 

  90. Anton L, Brosnihan KB (2008) Systemic and uteroplacental renin–angiotensin system in normal and pre-eclamptic pregnancies. Ther Adv Cardiovasc Dis 2(5):349–362. doi:10.1177/1753944708094529

    PubMed Central  PubMed  Google Scholar 

  91. Herse F, Staff AC, Hering L, Muller DN, Luft FC, Dechend R (2008) AT1-receptor autoantibodies and uteroplacental RAS in pregnancy and pre-eclampsia. J Mol Med (Berl) 86(6):697–703. doi:10.1007/s00109-008-0332-4

    CAS  Google Scholar 

  92. Hering L, Herse F, Geusens N, Verlohren S, Wenzel K, Staff AC, Brosnihan KB, Huppertz B, Luft FC, Muller DN, Pijnenborg R, Cartwright JE, Dechend R (2010) Effects of circulating and local uteroplacental angiotensin II in rat pregnancy. Hypertension 56(2):311–318. doi:10.1161/HYPERTENSIONAHA.110.150961

    CAS  PubMed  Google Scholar 

  93. Shah DM, Banu JM, Chirgwin JM, Tekmal RR (2000) Reproductive tissue renin gene expression in preeclampsia. Hypertens Pregnancy 19(3):341–351 pii:100101996

    CAS  PubMed  Google Scholar 

  94. Anton L, Merrill DC, Neves LA, Gruver C, Moorefield C, Brosnihan KB (2010) Angiotensin II and angiotensin-(1-7) decrease sFlt1 release in normal but not preeclamptic chorionic villi: an in vitro study. Reprod Biol Endocrinol 8:135. doi:10.1186/1477-7827-8-135

    PubMed Central  PubMed  Google Scholar 

  95. Mosca L, Benjamin EJ, Berra K, Bezanson JL, Dolor RJ, Lloyd-Jones DM, Newby LK, Pina IL, Roger VL, Shaw LJ, Zhao D, Beckie TM, Bushnell C, D’Armiento J, Kris-Etherton PM, Fang J, Ganiats TG, Gomes AS, Gracia CR, Haan CK, Jackson EA, Judelson DR, Kelepouris E, Lavie CJ, Moore A, Nussmeier NA, Ofili E, Oparil S, Ouyang P, Pinn VW, Sherif K, Smith SC Jr, Sopko G, Chandra-Strobos N, Urbina EM, Vaccarino V, Wenger NK (2011) Effectiveness-based guidelines for the prevention of cardiovascular disease in women—2011 update: a guideline from the american heart association. Circulation 123(11):1243–1262. doi:10.1161/CIR.0b013e31820faaf8

    PubMed Central  PubMed  Google Scholar 

  96. Irgens HU, Reisaeter L, Irgens LM, Lie RT (2001) Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. BMJ 323(7323):1213–1217

    CAS  PubMed Central  PubMed  Google Scholar 

  97. Bellamy L, Casas JP, Hingorani AD, Williams DJ (2007) Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ 335(7627):974. doi:10.1136/bmj.39335.385301.BE

    PubMed Central  PubMed  Google Scholar 

  98. Lykke JA, Langhoff-Roos J, Sibai BM, Funai EF, Triche EW, Paidas MJ (2009) Hypertensive pregnancy disorders and subsequent cardiovascular morbidity and type 2 diabetes mellitus in the mother. Hypertension 53(6):944–951. doi:10.1161/HYPERTENSIONAHA.109.130765

    CAS  PubMed  Google Scholar 

  99. Wikstrom AK, Haglund B, Olovsson M, Lindeberg SN (2005) The risk of maternal ischaemic heart disease after gestational hypertensive disease. BJOG 112(11):1486–1491. doi:10.1111/j.1471-0528.2005.00733.x

    PubMed  Google Scholar 

  100. Harsem NK, Roald B, Braekke K, Staff AC (2007) Acute atherosis in decidual tissue: not associated with systemic oxidative stress in preeclampsia. Placenta 28(8–9):958–964. doi:10.1016/j.placenta.2006.11.005

    CAS  PubMed  Google Scholar 

  101. Hanssens M, Pijnenborg R, Keirse MJ, Vercruysse L, Verbist L, Van Assche FA (1998) Renin-like immunoreactivity in uterus and placenta from normotensive and hypertensive pregnancies. Eur J Obstet Gynecol Reprod Biol 81(2):177–184

    CAS  PubMed  Google Scholar 

  102. Staff AC, Dechend R, Redman CW (2013) Review: preeclampsia, acute atherosis of the spiral arteries and future cardiovascular disease: two new hypotheses. Placenta 34(Suppl):S73–78. doi:10.1016/j.placenta.2012.11.022

    PubMed  Google Scholar 

  103. Staff AC, Redman CW (2014) IFPA Award in Placentology Lecture: preeclampsia, the decidual battleground and future maternal cardiovascular disease. Placenta 35(Suppl):S26–31. doi:10.1016/j.placenta.2013.12.003

    PubMed  Google Scholar 

  104. Tenhola S, Rahiala E, Martikainen A, Halonen P, Voutilainen R (2003) Blood pressure, serum lipids, fasting insulin, and adrenal hormones in 12-year-old children born with maternal preeclampsia. J Clin Endocrinol Metab 88(3):1217–1222. doi:10.1210/jc.2002-020903

    CAS  PubMed  Google Scholar 

  105. Vatten LJ, Romundstad PR, Holmen TL, Hsieh CC, Trichopoulos D, Stuver SO (2003) Intrauterine exposure to preeclampsia and adolescent blood pressure, body size, and age at menarche in female offspring. Obstet Gynecol 101(3):529–533 pii:S0029784402027187

    PubMed  Google Scholar 

  106. Oglaend B, Forman MR, Romundstad PR, Nilsen ST, Vatten LJ (2009) Blood pressure in early adolescence in the offspring of preeclamptic and normotensive pregnancies. J Hypertens 27(10):2051–2054. doi:10.1097/HJH.0b013e328330052a

    CAS  PubMed  Google Scholar 

  107. Ros HS, Lichtenstein P, Ekbom A, Cnattingius S (2001) Tall or short? Twenty years after preeclampsia exposure in utero: comparisons of final height, body mass index, waist-to-hip ratio, and age at menarche among women, exposed and unexposed to preeclampsia during fetal life. Pediatr Res 49(6):763–769. doi:10.1203/00006450-200106000-00008

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We apologize to the many authors whose excellent papers could not be cited in this review for space limitations. The work discussed in this review was supported by Deutsche Forschungsgemeinschaft (DFG) Grant BL1115/2-1 and Fritz Thyssen Stiftung (Az. 10.10.2.125) to S.M.B. The Research Council of Norway and Regional Health Authorities (South-Eastern Norway) to A.C.S; and G.B. is supported by the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, Argentina).

Author information

Authors and Affiliations

  1. Charité Center 12 Internal Medicine and Dermatology, Reproductive Medicine Research Group, Universitätsmedizin Berlin, Berlin, Germany

    Sandra M. Blois

  2. Experimental and Clinical Research Center (ECRC), Charité-Campus Buch-Max-Delbrück Center for Molecular Medicine and HELIOS Klinikum Berlin-Buch, Berlin, Germany

    Ralf Dechend

  3. Laboratorio de Medicina Experimental (LME), Hospital Alemán, Buenos Aires, Argentina

    Gabriela Barrientos

  4. Department of Obstetrics and Department of Gynaecology, Women and Children’s Division, Oslo University Hospital, Ullevål and University of Oslo, Oslo, Norway

    Anne Cathrine Staff

Authors
  1. Sandra M. Blois
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ralf Dechend
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gabriela Barrientos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anne Cathrine Staff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sandra M. Blois.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Blois, S.M., Dechend, R., Barrientos, G. et al. A potential pathophysiological role for galectins and the renin–angiotensin system in preeclampsia. Cell. Mol. Life Sci. 72, 39–50 (2015). https://doi.org/10.1007/s00018-014-1713-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-014-1713-1

Keywords

Search

Navigation