Skip to main content

Advertisement

SpringerLink
Log in

Placental Ischemia and Resultant Phenotype in Animal Models of Preeclampsia

  • Preeclampsia (V Garovic, Section Editor)
  • Published:
Current Hypertension Reports Aims and scope Submit manuscript

Abstract

Preeclampsia is new onset (or worsening of preexisting) hypertension that occurs during pregnancy. It is accompanied by chronic inflammation, intrauterine growth restriction, elevated anti-angiogenic factors, and can occur with or without proteinuria. Although the exact etiology is unknown, it is thought that preeclampsia begins early in gestation with reduced uterine spiral artery remodeling leading to decreased vasculogenesis of the placenta as the pregnancy progresses. Soluble factors, stimulated by the ischemic placenta, shower the maternal vascular endothelium and are thought to cause endothelial dysfunction and to contribute to the development of hypertension during pregnancy. Due to the difficulty in studying such soluble factors in pregnant women, various animal models have been designed. Studies from these models have contributed to a better understanding of how factors released in response to placental ischemia may lead to increased blood pressure and reduced fetal weight during pregnancy. This review will highlight various animal models and the major findings indicating the importance of placental ischemia to lead to the pathophysiology observed in preeclamptic patients.

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

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Keyes LE et al. Intrauterine growth restriction, preeclampsia, and intrauterine mortality at high altitude in Bolivia. Pediatr Res. 2003;54(1):20–5.

    Article  PubMed  Google Scholar 

  2. Powe CE, Levine RJ, Karumanchi SA. Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease. Circulation. 2011;123(24):2856–69.

    Article  PubMed  Google Scholar 

  3. Thadhani RI, Johnson RJ, Karumanchi SA. Hypertension during pregnancy: a disorder begging for pathophysiological support. Hypertension. 2005;46(6):1250–1.

    Article  CAS  PubMed  Google Scholar 

  4. Redman CW. Preeclampsia: a multi-stress disorder. Rev Med Interne. 2011;32 Suppl 1:S41–4.

    Article  PubMed  Google Scholar 

  5. Redman CW, Sargent L. Immunology of pre-eclampsia. Am J Reprod Immunol. 2010;63(6):534–43. Reviews the importance of immune cells and inflammation during normal pregnancy and preeclampsia, respectively

  6. Brown CE et al. Low-dose aspirin. II. Relationship of angiotensin II pressor responses, circulating eicosanoids, and pregnancy outcome. Am J Obstet Gynecol. 1990;163(6 Pt 1):1853–61.

    Article  CAS  PubMed  Google Scholar 

  7. Hladunewich M, Karumanchi SA, Lafayette R. Pathophysiology of the clinical manifestations of preeclampsia. Clin J Am Soc Nephrol. 2007;2(3):543–9.

    Article  PubMed  Google Scholar 

  8. Khalil RA, Granger JP. Vascular mechanisms of increased arterial pressure in preeclampsia: lessons from animal models. Am J Physiol Regul Integr Comp Physiol. 2002;283(1):R29–45.

    Article  CAS  PubMed  Google Scholar 

  9. Lunell NO et al. Uteroplacental blood flow in pregnancy induced hypertension. Scand J Clin Lab Investig Suppl. 1984;169:28–35.

    Article  CAS  Google Scholar 

  10. Li J, LaMarca B, Reckelhoff JF. A model of preeclampsia in rats: the reduced uterine perfusion pressure (RUPP) model. Am J Physiol Heart Circ Physiol. 2012;303(1):H1–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Gilbert JS et al. Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2008;294(2):H541–50.

    Article  CAS  PubMed  Google Scholar 

  12. Odegard RA et al. Preeclampsia and fetal growth. Obstet Gynecol. 2000;96(6):950–5.

    CAS  PubMed  Google Scholar 

  13. Roberts JM, Escudero C. The placenta in preeclampsia. Hypertens Pregnancy. 2012;2(2):72–83.

    CAS  Google Scholar 

  14. Ahmed A et al. Regulation of placental vascular endothelial growth factor (VEGF) and placenta growth factor (PIGF) and soluble Flt-1 by oxygen--a review. Placenta. 2000;21 Suppl A:S16–24.

    Article  CAS  PubMed  Google Scholar 

  15. Rodesch F et al. Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy. Obstet Gynecol. 1992;80(2):283–5.

    CAS  PubMed  Google Scholar 

  16. Zhou Y et al. Preeclampsia is associated with abnormal expression of adhesion molecules by invasive cytotrophoblasts. J Clin Invest. 1993;91(3):950–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Zhou Y et al. Human cytotrophoblasts adopt a vascular phenotype as they differentiate. A strategy for successful endovascular invasion? J Clin Invest. 1997;99(9):2139–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Mabie WC et al. A longitudinal study of cardiac output in normal human pregnancy. Am J Obstet Gynecol. 1994;170(3):849–56.

    Article  CAS  PubMed  Google Scholar 

  19. Jauniaux E, Burton GJ. Morphological and biological effects of maternal exposure to tobacco smoke on the feto-placental unit. Early Hum Dev. 2007;83(11):699–706.

    Article  CAS  PubMed  Google Scholar 

  20. Jauniaux E et al. Amniotic gas values and acid–base status during acute maternal hyperoxemia and hypoxemia in the early fetal sheep. Am J Obstet Gynecol. 2000;182(3):661–5.

    Article  CAS  PubMed  Google Scholar 

  21. Jauniaux E et al. In-vivo measurement of intrauterine gases and acid–base values early in human pregnancy. Hum Reprod. 1999;14(11):2901–4.

    Article  CAS  PubMed  Google Scholar 

  22. Lala PK, Chakraborty C. Factors regulating trophoblast migration and invasiveness: possible derangements contributing to pre-eclampsia and fetal injury. Placenta. 2003;24(6):575–87.

    Article  CAS  PubMed  Google Scholar 

  23. Wells M. The pathology of gestational trophoblastic disease: recent advances. Pathology. 2007;39(1):88–96.

    Article  PubMed  Google Scholar 

  24. King A. Uterine leukocytes and decidualization. Hum Reprod Update. 2000;6(1):28–36.

    Article  CAS  PubMed  Google Scholar 

  25. Trundley A, Moffett A. Human uterine leukocytes and pregnancy. Tissue Antigens. 2004;63(1):1–12.

    Article  CAS  PubMed  Google Scholar 

  26. Williams PJ et al. Decidual leucocyte populations in early to late gestation normal human pregnancy. J Reprod Immunol. 2009;82(1):24–31. Describes early immune pregnancy cell populations.

  27. Craven CM, Morgan T, Ward K. Decidual spiral artery remodelling begins before cellular interaction with cytotrophoblasts. Placenta. 1998;19(4):241–52.

    Article  CAS  PubMed  Google Scholar 

  28. Hanna J et al. Decidual NK cells regulate key developmental processes at the human fetal-maternal interface. Nat Med. 2006;12(9):1065–74.

    Article  CAS  PubMed  Google Scholar 

  29. Somerset DA et al. Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset. Immunology. 2004;112(1):38–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Tilburgs T et al. Evidence for a selective migration of fetus-specific CD4 + CD25bright regulatory T cells from the peripheral blood to the decidua in human pregnancy. J Immunol. 2008;180(8):5737–45. Describes specific methods for T cells stainings and populations in pregnancy.

  31. Veenstra van Nieuwenhoven AL, Heineman MJ, Faas MM, The immunology of successful pregnancy. Hum Reprod Update. 2003;9(4):347–57.

    Article  CAS  PubMed  Google Scholar 

  32. Freeman DJ et al. Short- and long-term changes in plasma inflammatory markers associated with preeclampsia. Hypertension. 2004;44(5):708–14.

    Article  CAS  PubMed  Google Scholar 

  33. LaMarca B, Cornelius D, Wallace K. Elucidating immune mechanisms causing hypertension during pregnancy. Physiology (Bethesda). 2013;28(4):225–33.

    CAS  Google Scholar 

  34. Cornelius DC et al. Administration of interleukin-17 soluble receptor C suppresses TH17 cells, oxidative stress, and hypertension in response to placental ischemia during pregnancy. Hypertension. 2013;62(6):1068–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Irani RA et al. Autoantibody-mediated angiotensin receptor activation contributes to preeclampsia through tumor necrosis factor-alpha signaling. Hypertension. 2010;55(5):1246–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Prins JR et al. Preeclampsia is associated with lower percentages of regulatory T cells in maternal blood. Hypertens Pregnancy. 2009;28(3):300–11.

    Article  PubMed  Google Scholar 

  37. Santner-Nanan B et al. Systemic increase in the ratio between Foxp3+ and IL-17-producing CD4+ T cells in healthy pregnancy but not in preeclampsia. J Immunol. 2009;183(11):7023–30. First description of changes in T regs and TH17 during PE.

  38. Wallace K et al. CD4+ T-helper cells stimulated in response to placental ischemia mediate hypertension during pregnancy. Hypertension. 2011;57(5):949–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Conrad KP, Benyo DF. Placental cytokines and the pathogenesis of preeclampsia. Am J Reprod Immunol. 1997;37(3):240–9.

    Article  CAS  PubMed  Google Scholar 

  40. Dhillion P et al. IL-17-mediated oxidative stress is an important stimulator of AT1-AA and hypertension during pregnancy. Am J Physiol Regul Integr Comp Physiol. 2012;303(4):R353–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Granger JP et al. Pathophysiology of hypertension during preeclampsia linking placental ischemia with endothelial dysfunction. Hypertension. 2001;38(3 Pt 2):718–22.

    Article  CAS  PubMed  Google Scholar 

  42. Granger JP et al. Pathophysiology of preeclampsia: linking placental ischemia/hypoxia with microvascular dysfunction. Microcirculation. 2002;9(3):147–60.

    Article  CAS  PubMed  Google Scholar 

  43. LaMarca BB et al. Role of endothelin in mediating tumor necrosis factor-induced hypertension in pregnant rats. Hypertension. 2005;46(1):82–6.

    Article  CAS  PubMed  Google Scholar 

  44. LaMarca BD et al. Pathophysiology of hypertension in response to placental ischemia during pregnancy: a central role for endothelin? Gend Med. 2008;5 Suppl A:S133–8.

    Article  PubMed  Google Scholar 

  45. Herse F, LaMarca B. Angiotensin II type 1 receptor autoantibody (AT1-AA)-mediated pregnancy hypertension. Am J Reprod Immunol. 2013;69(4):413–8.

    Article  CAS  PubMed  Google Scholar 

  46. LaMarca B, Wallace K, Granger J. Role of angiotensin II type I receptor agonistic autoantibodies (AT1-AA) in preeclampsia. Curr Opin Pharmacol. 2011;11(2):175–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Parrish MR et al. Angiotensin II type 1 autoantibody induced hypertension during pregnancy is associated with renal endothelial dysfunction. Gend Med. 2011;8(3):184–8.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Wenzel K et al. Angiotensin II type 1 receptor antibodies and increased angiotensin II sensitivity in pregnant rats. Hypertension. 2011;58(1):77–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhou CC 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(4):1010–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Podjarny E, Losonczy G, Baylis C. Animal models of preeclampsia. Semin Nephrol. 2004;24(6):596–606.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Abitbol MM. A simplified technique to produce toxemia in the pregnant dog. Am J Obstet Gynecol. 1981;139(5):526–34.

    Article  CAS  PubMed  Google Scholar 

  52. Woods LL, Brooks VL. Role of the renin-angiotensin system in hypertension during reduced uteroplacental perfusion pressure. Am J Physiol. 1989;257(1 Pt 2):R204–9.

    CAS  PubMed  Google Scholar 

  53. Abitbol MM, Driscoll SG, Ober WB. Placental lesions in experimental toxemia in the rabbit. Am J Obstet Gynecol. 1976;125(7):942–8.

    Article  CAS  PubMed  Google Scholar 

  54. Abitbol MM et al. Production of experimental toxemia in the pregnant rabbit. Am J Obstet Gynecol. 1976;124(5):460–70.

    Article  CAS  PubMed  Google Scholar 

  55. Combs CA et al. Experimental preeclampsia produced by chronic constriction of the lower aorta: validation with longitudinal blood pressure measurements in conscious rhesus monkeys. Am J Obstet Gynecol. 1993;169(1):215–23.

    Article  CAS  PubMed  Google Scholar 

  56. Zhou Y et al. Increased depth of trophoblast invasion after chronic constriction of the lower aorta in rhesus monkeys. Am J Obstet Gynecol. 1993;169(1):224–9.

    Article  CAS  PubMed  Google Scholar 

  57. Cavanagh D et al. Pregnancy-induced hypertension: development of a model in the pregnant primate (Papio anubis). Am J Obstet Gynecol. 1985;151(7):987–99.

    Article  CAS  PubMed  Google Scholar 

  58. Crews JK et al. Decreased endothelium-dependent vascular relaxation during reduction of uterine perfusion pressure in pregnant rat. Hypertension. 2000;35(1 Pt 2):367–72.

    Article  CAS  PubMed  Google Scholar 

  59. Alexander BT et al. Reduced uterine perfusion pressure during pregnancy in the rat is associated with increases in arterial pressure and changes in renal nitric oxide. Hypertension. 2001;37(4):1191–5.

    Article  CAS  PubMed  Google Scholar 

  60. Murphy JG et al. Enhanced [Ca2+]i in renal arterial smooth muscle cells of pregnant rats with reduced uterine perfusion pressure. Am J Physiol Heart Circ Physiol. 2003;284(1):H393–403.

    Article  CAS  PubMed  Google Scholar 

  61. Roberts L et al. Enhanced endothelin synthesis by endothelial cells exposed to sera from pregnant rats with decreased uterine perfusion. Hypertension. 2006;47(3):615–8.

    Article  CAS  PubMed  Google Scholar 

  62. Alexander BT et al. Tumor necrosis factor-alpha-induced hypertension in pregnant rats results in decreased renal neuronal nitric oxide synthase expression. Am J Hypertens. 2002;15(2 Pt 1):170–5.

    Article  CAS  PubMed  Google Scholar 

  63. Wallukat G et al. Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest. 1999;103(7):945–52. First description of AT1-AA during PE.

  64. Sedeek M et al. Role of reactive oxygen species in hypertension produced by reduced uterine perfusion in pregnant rats. Am J Hypertens. 2008;21(10):1152–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Gilbert JS, Babcock SA, Granger JP. Hypertension produced by reduced uterine perfusion in pregnant rats is associated with increased soluble fms-like tyrosine kinase-1 expression. Hypertension. 2007;50(6):1142–7.

    Article  CAS  PubMed  Google Scholar 

  66. Gilbert JS et al. Hypertension produced by placental ischemia in pregnant rats is associated with increased soluble endoglin expression. Hypertension. 2009;53(2):399–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Kupferminc MJ et al. Tumor necrosis factor-alpha is elevated in plasma and amniotic fluid of patients with severe preeclampsia. Am J Obstet Gynecol. 1994;170(6):1752–7. discussion 1757–9.

    Article  CAS  PubMed  Google Scholar 

  68. Gadonski G et al. Hypertension produced by reductions in uterine perfusion in the pregnant rat: role of interleukin 6. Hypertension. 2006;48(4):711–6.

    Article  CAS  PubMed  Google Scholar 

  69. Heikkinen J et al. Phenotypic characterization of regulatory T cells in the human decidua. Clin Exp Immunol. 2004;136(2):373–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Saito S et al. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am J Reprod Immunol. 2010;63(6):601–10.

    Article  CAS  PubMed  Google Scholar 

  71. Sakaguchi S et al. Regulatory T cells and immune tolerance. Cell. 2008;133(5):775–87.

    Article  CAS  PubMed  Google Scholar 

  72. Sasaki Y et al. Decidual and peripheral blood CD4 + CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod. 2004;10(5):347–53.

    Article  CAS  PubMed  Google Scholar 

  73. Lash GE, Robson SC, Bulmer JN. Review: functional role of uterine natural killer (uNK) cells in human early pregnancy decidua. Placenta. 2010;31(Suppl):S87–92.

    Article  PubMed  CAS  Google Scholar 

  74. Munoz-Suano A, Hamilton AB, Betz AG. Gimme shelter: the immune system during pregnancy. Immunol Rev. 2011;241(1):20–38.

    Article  CAS  PubMed  Google Scholar 

  75. Tilburgs T et al. Expression of NK cell receptors on decidual T cells in human pregnancy. J Reprod Immunol. 2009;80(1–2):22–32.

    Article  CAS  PubMed  Google Scholar 

  76. Zenclussen AC et al. Introducing a mouse model for pre-eclampsia: adoptive transfer of activated Th1 cells leads to pre-eclampsia-like symptoms exclusively in pregnant mice. Eur J Immunol. 2004;34(2):377–87.

    Article  CAS  PubMed  Google Scholar 

  77. Novotny SR et al. 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. 2012;302(10):R1197–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Novotny S, et al. CD4 T cells play a critical role in mediating hypertension in response to placental ischemia. J Hypertens (Los Angel). 2013;2.

  79. Cornelius DC, et al. Administration of interleukin-17 soluble receptor C suppresses TH17 cells, oxidative stress, and hypertension in response to placental ischemia during pregnancy. Hypertension. 2013.

  80. Kleinewietfeld M, Hafler DA. Regulatory T cells in autoimmune neuroinflammation. Immunol Rev. 2014;259(1):231–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Quinn KH et al. The unique pathophysiology of early-onset severe preeclampsia: role of decidual T regulatory cells. J Reprod Immunol. 2011;91(1–2):76–82.

    Article  CAS  PubMed  Google Scholar 

  82. Sasaki Y et al. Proportion of peripheral blood and decidual CD4(+) CD25(bright) regulatory T cells in pre-eclampsia. Clin Exp Immunol. 2007;149(1):139–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. von Rango U. Fetal tolerance in human pregnancy--a crucial balance between acceptance and limitation of trophoblast invasion. Immunol Lett. 2008;115(1):21–32.

    Article  CAS  Google Scholar 

  84. Zenclussen AC et al. Abnormal T-cell reactivity against paternal antigens in spontaneous abortion: adoptive transfer of pregnancy-induced CD4 + CD25+ T regulatory cells prevents fetal rejection in a murine abortion model. Am J Pathol. 2005;166(3):811–22.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Aluvihare VR, Kallikourdis M, Betz AG. Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol. 2004;5(3):266–71.

    Article  CAS  PubMed  Google Scholar 

  86. Redman CW et al. Review: does size matter? Placental debris and the pathophysiology of pre-eclampsia. Placenta. 2012;33(Suppl):S48–54.

    Article  PubMed  Google Scholar 

  87. Chamley LW et al. Trophoblast deportation: just a waste disposal system or antigen sharing? J Reprod Immunol. 2011;88(2):99–105.

    Article  CAS  PubMed  Google Scholar 

  88. Lau SY et al. Necrotic trophoblast debris increases blood pressure during pregnancy. J Reprod Immunol. 2013;97(2):175–82.

    Article  PubMed  Google Scholar 

  89. Hubel CA et al. Agonistic angiotensin II type 1 receptor autoantibodies in postpartum women with a history of preeclampsia. Hypertension. 2007;49(3):612–7.

    Article  CAS  PubMed  Google Scholar 

  90. Brewer J et al. Endothelin-1, oxidative stress, and endogenous angiotensin II: mechanisms of angiotensin II type I receptor autoantibody-enhanced renal and blood pressure response during pregnancy. Hypertension. 2013;62(5):886–92.

    Article  CAS  PubMed  Google Scholar 

  91. LaMarca B et al. Hypertension in response to autoantibodies to the angiotensin II type I receptor (AT1-AA) in pregnant rats: role of endothelin-1. Hypertension. 2009;54(4):905–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Parrish MR et al. The effect of immune factors, tumor necrosis factor-alpha, and agonistic autoantibodies to the angiotensin II type I receptor on soluble fms-like tyrosine-1 and soluble endoglin production in response to hypertension during pregnancy. Am J Hypertens. 2010;23(8):911–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Parrish MR et al. Hypertension in response to AT1-AA: role of reactive oxygen species in pregnancy-induced hypertension. Am J Hypertens. 2011;24(7):835–40.

    Article  CAS  PubMed  Google Scholar 

  94. Xia Y, Kellems RE. Angiotensin receptor agonistic autoantibodies and hypertension: preeclampsia and beyond. Circ Res. 2013;113(1):78–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Quitterer U, Lother H, Abdalla S. AT1 receptor heterodimers and angiotensin II responsiveness in preeclampsia. Semin Nephrol. 2004;24(2):115–9.

    Article  CAS  PubMed  Google Scholar 

  96. AbdAlla S et al. Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat Med. 2001;7(9):1003–9.

    Article  CAS  PubMed  Google Scholar 

  97. Nagamatsu T et al. Cytotrophoblasts up-regulate soluble fms-like tyrosine kinase-1 expression under reduced oxygen: an implication for the placental vascular development and the pathophysiology of preeclampsia. Endocrinology. 2004;145(11):4838–45.

    Article  CAS  PubMed  Google Scholar 

  98. Nevo O et al. Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1. Am J Physiol Regul Integr Comp Physiol. 2006;291(4):R1085–93.

    Article  CAS  PubMed  Google Scholar 

  99. Makris A et al. Uteroplacental ischemia results in proteinuric hypertension and elevated sFLT-1. Kidney Int. 2007;71(10):977–84.

    Article  CAS  PubMed  Google Scholar 

  100. Maynard SE 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(5):649–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Bridges JP et al. Oxidative stress contributes to soluble fms-like tyrosine kinase-1 induced vascular dysfunction in pregnant rats. Am J Hypertens. 2009;22(5):564–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Murphy SR et al. Role of endothelin in mediating soluble fms-like tyrosine kinase 1-induced hypertension in pregnant rats. Hypertension. 2010;55(2):394–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Li Z et al. Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia. Hypertension. 2007;50(4):686–92.

    Article  CAS  PubMed  Google Scholar 

  104. Bergmann A et al. Reduction of circulating soluble Flt-1 alleviates preeclampsia-like symptoms in a mouse model. J Cell Mol Med. 2010;14(6B):1857–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Murphy S et al. Role of endothelin in mediating soluble fms-like tyrosine kinase 1 induced hypertension in pregnant rats. Hypertension. 2010;55:394–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Gilbert JS et al. Recombinant vascular endothelial growth factor 121 infusion lowers blood pressure and improves renal function in rats with placental ischemia-induced hypertension. Hypertension. 2010;55(2):380–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Davisson RL et al. Discovery of a spontaneous genetic mouse model of preeclampsia. Hypertension. 2002;39(2 Pt 2):337–42.

    Article  CAS  PubMed  Google Scholar 

  108. Wallace K et al. Hypertension in response to CD4(+) T cells from reduced uterine perfusion pregnant rats is associated with activation of the endothelin-1 system. Am J Physiol Regul Integr Comp Physiol. 2012;303(2):R144–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Woods AK et al. Adenoviral delivery of VEGF121 early in pregnancy prevents spontaneous development of preeclampsia in BPH/5 mice. Hypertension. 2011;57(1):94–102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Shah DM. Role of the renin-angiotensin system in the pathogenesis of preeclampsia. Am J Physiol Ren Physiol. 2005;288(4):F614–25.

    Article  CAS  Google Scholar 

  111. Takimoto E et al. Hypertension induced in pregnant mice by placental renin and maternal angiotensinogen. Science. 1996;274(5289):995–8.

    Article  CAS  PubMed  Google Scholar 

  112. 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(11):2056–61.

    CAS  PubMed  Google Scholar 

  113. Verlohren S et al. Uterine vascular function in a transgenic preeclampsia rat model. Hypertension. 2008;51(2):547–53.

    Article  CAS  PubMed  Google Scholar 

  114. Falcao S et al. Mice overexpressing both human angiotensinogen and human renin as a model of superimposed preeclampsia on chronic hypertension. Hypertension. 2009;54(6):1401–7.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Pharmacology, Physiology, & Ob/Gyn, Center for Excellence in Cardiovascular and Renal Research, University of Mississippi Medical Center, Jackson, MS, 39216, USA

    Babbette LaMarca, Lorena M. Amaral, Ashlyn C. Harmon, Denise C. Cornelius, Jessica L. Faulkner & Mark W. Cunningham Jr

Authors
  1. Babbette LaMarca
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lorena M. Amaral
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ashlyn C. Harmon
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Denise C. Cornelius
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jessica L. Faulkner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mark W. Cunningham Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Babbette LaMarca.

Ethics declarations

Conflict of Interest

Drs. LaMarca, Amaral, Harmon, Cornelius, Jessica, and Cunningham declare no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Preeclampsia

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

LaMarca, B., Amaral, L.M., Harmon, A.C. et al. Placental Ischemia and Resultant Phenotype in Animal Models of Preeclampsia. Curr Hypertens Rep 18, 38 (2016). https://doi.org/10.1007/s11906-016-0633-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11906-016-0633-x

Keywords

Search

Navigation