Placenta
Volume 29, Issue 9 , Pages 763-771 , September 2008

The Functional Role of the Renin–Angiotensin System in Pregnancy and Preeclampsia

  • R.A. Irani
  • ,
  • Y. Xia

      Affiliations

    • Corresponding Author InformationCorresponding author. Tel.: +1 713 500 5039; fax: +1 713 500 0652.

,Accepted 23 June 2008.

References 

  1. Jensen BL, Schmid C, Kurtz A. Prostaglandins stimulate renin secretion and renin mRNA in mouse renal juxtaglomerular cells. Am J Physiol. 1996;271(3 Pt 2):F659–F669
  2. Chung O, Kuhl H, Stoll M, Unger T. Physiological and pharmacological implications of AT1 versus AT2 receptors. Kidney Int. 1998;54(S67):S95–S99
  3. Ozono R, Wang ZQ, Moore AF, Inagami T, Siragy HM, Carey RM. Expression of the subtype 2 angiotensin (AT2) receptor protein in rat kidney. Hypertension. 1997;30(5):1238–1246
  4. Grishko V, Pastukh V, Solodushko V, Gillespie M, Azuma J, Schaffer S. Apoptotic cascade initiated by angiotensin II in neonatal cardiomyocytes: role of DNA damage. Am J Physiol Heart Circ Physiol. 2003;285(6):H2364–H2372
  5. Wang Y, Gu Y, Zhang Y, Lewis DF, Alexander JS, Granger DN. Increased chymotrypsin-like protease (chymase) expression and activity in placentas from women with preeclampsia. Placenta. 2007;28(4):263–269
  6. Urata H, Kinoshita A, Misono KS, Bumpus FM, Husain A. Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J Biol Chem. 1990;265(36):22348–22357
  7. Caughey GH, Schaumberg TH, Zerweck EH, Butterfield JH, Hanson RD, Silverman GA, et al. The human mast cell chymase gene (CMA1): mapping to the cathepsin G/granzyme gene cluster and lineage-restricted expression. Genomics. 1993;15(3):614–620
  8. Hagemann A, Nielsen AH, Poulsen K. The uteroplacental renin-angiotensin system: a review. Exp Clin Endocrinol. 1994;102(3):252–261
  9. Poisner AM. The human placental renin-angiotensin system. Front Neuroendocrinol. 1998;19(3):232–252
  10. Hodari AA, Smeby R, Bumpus FM. A renin-like substance in the human placenta. Obstet Gynecol. 1967;29(3):313–317
  11. Symonds EM, Stanley MA, Skinner SL. Production of renin by in vitro cultures of human chorion and uterine muscle. Nature. 1968;217(5134):1152–1153
  12. Li X, Shams M, Zhu J, Khalig A, Wilkes M, Whittle M, et al. Cellular localization of AT1 receptor mRNA and protein in normal placenta and its reduced expression in intrauterine growth restriction. Angiotensin II stimulates the release of vasorelaxants. J Clin Invest. 1998;101(2):442–454
  13. Shaw KJ, Do YS, Kjos S, Anderson PW, Shinagawa T, Dubeau L, et al. Human decidua is a major source of renin. J Clin Invest. 1989;83(6):2085–2092
  14. Li C, Ansari R, Yu Z, Shah D. Definitive molecular evidence of renin-angiotensin system in human uterine decidual cells. Hypertension. 2000;36(2):159–164
  15. Morgan T, Craven C, Ward K. Human spiral artery renin-angiotensin system. Hypertension. 1998;32(4):683–687
  16. Hsueh WA, Luetscher JA, Carlson EJ, Grislis G, Fraze E, McHargue A. Changes in active and inactive renin throughout pregnancy. J Clin Endocrinol Metab. 1982;54(5):1010–1016
  17. Brown MA, Gallery ED, Ross MR, Esber RP. Sodium excretion in normal and hypertensive pregnancy: a prospective study. Am J Obstet Gynecol. 1988;159(2):297–307
  18. Merrill DC, Karoly M, Chen K, Ferrario CM, Brosnihan KB. Angiotensin-(1–7) in normal and preeclamptic pregnancy. Endocrine. 2002;18(3):239–245
  19. Assali NS, Westersten A. Regional flow-pressure relationship in response to angiotensin in the intact dog and sheep. Circ Res. 1961;9:189–193
  20. Gant NF, Worley RJ, Everett RB, MacDonald PC. Control of vascular responsiveness during human pregnancy. Kidney Int. 1980;18(2):253–258
  21. AbdAlla S, Lother H, el Massiery A, Quitterer U. Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nat Med. 2001;7(9):1003–1009
  22. Dechend R, Viedt C, Muller DN, Ugele B, Brandes RP, Wallukat G, et al. AT1 receptor agonistic antibodies from preeclamptic patients stimulate NADPH oxidase. Circulation. 2003;107(12):1632–1639
  23. Shibata E, Powers RW, Rajakumar A, von Versen-Hoynck F, Gallaher MJ, Lykins DL, et al. Angiotensin II decreases system A amino acid transporter activity in human placental villous fragments through AT1 receptor activation. Am J Physiol Endocrinol Metab. 2006;291(5):E1009–E1016
  24. Takimoto E, Ishida J, Sugiyama F, Horiguchi H, Murakami K, Fukamizu A. Hypertension induced in pregnant mice by placental renin and maternal angiotensinogen. Science. 1996;274(5289):995–998
  25. Xia Y, Wen H, Prashner HR, Chen R, Inagami T, Catanzaro DF, et al. Pregnancy-induced changes in renin gene expression in mice. Biol Reprod. 2002;66(1):135–143
  26. Roberts JM. Endothelial dysfunction in preeclampsia. Semin Reprod Endocrinol. 1998;16:5–15
  27. Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005;308(5728):1592–1594
  28. Santos RA, Haibara AS, Campagnole-Santos MJ, Simoes e Silva AC, Paula RD, Pinheiro SV, et al. Characterization of a new selective antagonist for angiotensin-(1–7), D-pro7-angiotensin-(1–7). Hypertension. 2003;41(3 Pt 2):737–743
  29. Handa RK. Angiotensin-(1-7) can interact with the rat proximal tubule AT(4) receptor system. Am J Physiol. 1999;277(1 Pt 2):F75–F83
  30. Handa RK. Metabolism alters the selectivity of angiotensin-(1–7) receptor ligands for angiotensin receptors. J Am Soc Nephrol. 2000;11(8):1377–1386
  31. Gant NF, Daley GL, Chand S, Whalley PJ, MacDonald PC. A study of angiotensin II pressor response throughout primigravid pregnancy. J Clin Invest. 1973;52(11):2682–2689
  32. Quitterer U, Lother H, Abdalla S. AT1 receptor heterodimers and angiotensin II responsiveness in preeclampsia. Semin Nephrol. 2004;24(2):115–119
  33. AbdAlla S, Abdel-Baset A, Lother H, el Massiery A, Quitterer U. Mesangial AT1/B2 receptor heterodimers contribute to angiotensin II hyperresponsiveness in experimental hypertension. J Mol Neurosci. 2005;26(2-3):185–192
  34. Ariza AC, Bobadilla NA, Halhali A. [Endothelin 1 and angiotensin II in preeeclampsia]. Rev Invest Clin. 2007;59(1):48–56
  35. Herse F, Dechend R, Harsem NK, Wallukat G, Janke J, Qadri F, et al. Dysregulation of the circulating and tissue-based renin-angiotensin system in preeclampsia. Hypertension. 2007;49(3):604–611
  36. Shah DM, Banu JM, Chirgwin JM, Tekmal RR. Reproductive tissue renin gene expression in preeclampsia. Hypertens Pregnancy. 2000;19(3):341–351
  37. Anton L, Merrill DC, Neves LA, Stovall K, Gallagher PE, Diz DI, et al. Activation of Local chorionic villi angiotensin II levels but not angiotensin (1–7) in preeclampsia. Hypertension. 2008;51(4):1066–1072
  38. Schechter NM, Wang ZM, Blacher RW, Lessin SR, Lazarus GS, Rubin H. Determination of the primary structures of human skin chymase and cathepsin G from cutaneous mast cells of urticaria pigmentosa lesions. J Immunol. 1994;152(8):4062–4069
  39. Muto T, Fukami H. Recent chymase inhibitors and their effects in in vivo models. IDrugs. 2002;5(12):1141–1150
  40. Ju H, Gros R, You X, Tsang S, Husain M, Rabinovitch M. Conditional and targeted overexpression of vascular chymase causes hypertension in transgenic mice. Proc Natl Acad Sci U S A. 2001;98(13):7469–7474
  41. Nakano A, Kishi F, Minami K, Wakabayashi H, Nakaya Y, Kido H. Selective conversion of big endothelins to tracheal smooth muscle-constricting 31-amino acid-length endothelins by chymase from human mast cells. J Immunol. 1997;159(4):1987–1992
  42. Mitani R, Maeda K, Fukui R, Endo S, Saijo Y, Shinohara K, et al. Production of human mast cell chymase in human myometrium and placenta in cases of normal pregnancy and preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2002;101(2):155–160
  43. Takeji T, Nakaya Y, Kamada M, Maeda K, Saijo Y, Mitani R, et al. Effect of a novel vasoconstrictor endothelin-1 (1–31) on human umbilical artery. Biochem Biophys Res Commun. 2000;270(2):622–624
  44. Wallukat G, Homuth V, Fischer T, Lindschau C, Horstkamp B, Jupner A, et al. Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest. 1999;103:945–952
  45. Karumanchi SA, Epstein FH. Placental ischemia and soluble fms-like tyrosine kinase 1: cause or consequence of preeclampsia?. Kidney Int. 2007;71(10):959–961
  46. Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350:672–683
  47. Kendall RL, Thomas KA. Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor. Proc Natl Acad Sci U S A. 1993;90:10705–10709
  48. Kendall RL, Wang G, Thomas KA. Identification of a natural soluble form of the vascular endothelial growth factor receptor, FLT-1, and its heterodimerization with KDR. Biochem Biophys Res Commun. 1996;226(2):324–328
  49. Shibuya M. Structure and function of VEGF/VEGF-receptor system involved in angiogenesis. Cell Struct Funct. 2001;26(1):25–35
  50. Zhou Y, McMaster M, Woo K, Janatpour M, Perry J, Karpanen T, et al. Vascular endothelial growth factor ligands and receptors that regulate human cytotrophoblast survival are dysregulated in severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets syndrome. Am J Pathol. 2002;160:1405–1423
  51. Tsatsaris V, Goffin F, Munaut C, Brichant J-F, Pignon M-R, Noel A, et al. Overexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: pathophysiological consequences. J Clin Endocrinol Metab. 2003;88:5555–5563
  52. Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, 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):649–658
  53. Nagamatsu T, Fujii T, Kusumi M, Zou L, Yamashita T, Osuga Y, 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;145:4838–4845
  54. Khaliq A, Dunk C, Jiang J, Shams M, Li XF, Acevedo C, et al. Hypoxia down-regulates placenta growth factor, whereas fetal growth restriction up-regulates placenta growth factor expression: molecular evidence for “placental hyperoxia” in intrauterine growth restriction. Lab Invest. 1999;79(2):151–170
  55. Ahmed A, Dunk C, Ahmad S, Khaliq A. 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–S24
  56. Lash GE, Taylor CM, Trew AJ, Cooper S, Anthony FW, Wheeler T, et al. Vascular endothelial growth factor and placental growth factor release in cultured trophoblast cells under different oxygen tensions. Growth Factors. 2002;20(4):189–196
  57. Karumanchi SA, Bdolah Y. Hypoxia and sFlt-1 in preeclampsia: the “chicken-and-egg” question. Endocrinology. 2004;145:4835–4837
  58. Caniggia I, Grisaru-Gravnosky S, Kuliszewsky M, Post M, Lye SJ. Inhibition of TGF-beta 3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies. J Clin Invest. 1999;103(12):1641–1650
  59. Caniggia I, Mostachfi H, Winter J, Gassmann M, Lye SJ, Kuliszewski M, et al. Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFbeta(3). J Clin Invest. 2000;105(5):577–587
  60. Soleymanlou N, Jurisica I, Nevo O, Ietta F, Zhang X, Zamudio S, et al. Molecular evidence of placental hypoxia in preeclampsia. J Clin Endocrinol Metab. 2005;90(7):4299–4308
  61. Zhou CC, Ahmad S, Mi T, Abbasi S, Xia L, Day MC, 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):1010–1019
  62. Zhou CC, Ahmad S, Mi T, Xia L, Abbasi S, Hewett PW, et al. Angiotensin II induces soluble fms-like tyrosine kinase-1 release via calcineurin signaling pathway in pregnancy. Circ Res. 2007;100(1):88–95
  63. Bobst SM, Day MC, Gilstrap LC, Xia Y, Kellems RE. 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(3):330–336
  64. Xia Y, Wen H, Bobst S, Day MC, Kellems RE. Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human trophoblast cells. J Soc Gynecol Invest. 2003;10(2):82–93
  65. Xia Y, Wen HY, Kellems RE. Angiotensin II inhibits human trophoblast invasion through AT1 receptor activation. J Biol Chem. 2002;277(27):24601–24608
  66. Gutteridge JM, Halliwell B. Free radicals and antioxidants in the year 2000. A historical look to the future. Ann N Y Acad Sci. 2000;899:136–147
  67. Burton GJ, Hempstock J, Jauniaux E. Oxygen, early embryonic metabolism and free radical-mediated embryopathies. Reprod Biomed Online. 2003;6(1):84–96
  68. van Tuyl M, Liu J, Wang J, Kuliszewski M, Tibboel D, Post M. Role of oxygen and vascular development in epithelial branching morphogenesis of the developing mouse lung. Am J Physiol Lung Cell Mol Physiol. 2005;288(1):L167–L178
  69. Hubel CA. Oxidative stress in the pathogenesis of preeclampsia. Proc Soc Exp Biol Med. 1999;222(3):222–235
  70. Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol. 1989;161(5):1200–1204
  71. Fay WP. Plasminogen activator inhibitor 1, fibrin, and the vascular response to injury. Trends Cardiovasc Med. 2004;14(5):196–202
  72. Nakamura S, Nakamura I, Ma L, Vaughan DE, Fogo AB. Plasminogen activator inhibitor-1 expression is regulated by the angiotensin type 1 receptor in vivo. Kidney Int. 2000;58(1):251–259
  73. Fogo AB. The role of angiotensin II and plasminogen activator inhibitor-1 in progressive glomerulosclerosis. Am J Kidney Dis. 2000;35(2):179–188
  74. Petrucco OM, Thomson NM, Lawrence JR, Weldon MW. Immunofluorescent studies in renal biopsies in pre-eclampsia. BMJ. 1974;1(5906):473–476
  75. Packham DK, Mathews DC, Fairley KF, Whitworth JA, Kincaid-Smith PS. Morphometric analysis of pre-eclampsia in women biopsied in pregnancy and post-partum. Kidney Int. 1988;34(5):704–711
  76. Erlich JH, Holdsworth SR, Tipping PG. Tissue factor initiates glomerular fibrin deposition and promotes major histocompatibility complex class II expression in crescentic glomerulonephritis. Am J Pathol. 1997;150(3):873–880
  77. Xu Y, Berrou J, Chen X, Fouqueray B, Callard P, Sraer JD, et al. Induction of urokinase receptor expression in nephrotoxic nephritis. Exp Nephrol. 2001;9(6):397–404
  78. Haller H OT, Hauck U, Distler A, Philipp T. Increased intracellular free calcium and sensitivity to angiotensin II in platelets of preeclamptic women. Am J Hypertens. 1989;2(4):238–243
  79. Hojo M, Suthanthiran M, Helseth G, August P. Lymphocyte intracellular free calcium concentration is increased in preeclampsia. Am J Obstet Gynecol. 1999;180(5):1209–1214
  80. Ray J, Vasishta K, Kaur S, Majumdar S, Sawhney H. Calcium metabolism in pre-eclampsia. Int J Gynaecol Obstet. 1999;66(3):245–250
  81. Sowers JR, Zemel MB, Bronsteen RA, Zemel PC, Walsh MF, Standley PR, et al. Erythrocyte cation metabolism in preeclampsia. Am J Obstet Gynecol. 1989;161(2):441–445
  82. Thway TM, Shlykov SG, Day MC, Sanborn BM, Gilstrap LC, Xia Y, et al. Antibodies from preeclamptic patients stimulate increased intracellular Ca2+ mobilization through angiotensin receptor activation. Circulation. 2004;110(12):1612–1619
  83. Dechend R, Homuth V, Wallukat G, Kreuzer J, Park JK, Theuer J, et al. AT(1) receptor agonistic antibodies from preeclamptic patients cause vascular cells to express tissue factor. Circulation. 2000;101(20):2382–2387
  84. Dorffel Y, Wallukat G, Bochnig N, Homuth V, Herberg M, Dorffel W, et al. Agonistic AT(1) receptor autoantibodies and monocyte stimulation in hypertensive patients. Am J Hypertens. 2003;16(10):827–833
  85. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007;335(7627):974
  86. Fu ML, Herlitz H, Schulze W, Wallukat G, Micke P, Eftekhari P, et al. Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension. J Hypertens. 2000;18(7):945–953
  87. Georgiades P, Ferguson-Smith AC, Burton GJ. Comparative developmental anatomy of the murine and human definitive placentae. Placenta. 2002;23(1):3–19
  88. Saito T, Ishida J, Takimoto-Ohnishi E, Takamine S, Shimizu T, Sugaya T, et al. An essential role for angiotensin II type 1a receptor in pregnancy-associated hypertension with intrauterine growth retardation. FASEB J. 2004;18(2):388–390
  89. Dechend R, Gratze P, Wallukat G, Shagdarsuren E, Plehm R, Brasen JH, et al. Agonistic autoantibodies to the AT1 receptor in a transgenic rat model of preeclampsia. Hypertension. 2005;45(4):742–746
  90. Granger JP, LaMarca BB, Cockrell K, Sedeek M, Balzi C, Chandler D, et al. Reduced uterine perfusion pressure (RUPP) model for studying cardiovascular-renal dysfunction in response to placental ischemia. Methods Mol Med. 2006;122:383–392
  91. Dechend R, Llinas M, Caluwaerts S, Herse F, Lamarca B, Mueller DN, et al. Agonistic autoantibodies to the AT1 receptor in rat models of preeclampsia: induced by chronic reduction in uterine perfusion pressure (RUPP) and low dose TNF-a infusion. Hypertens Pregnancy. 2006;25:70;[abstract]
  92. Pearce SH, Merriman TR. Genetic progress towards the molecular basis of autoimmunity. Trends Mol Med. 2006;12:90–98
  93. Fujinami RS, von Herrath MG, Christen U, Whitton JL. Molecular mimicry, bystander activation, or viral persistence: infections and autoimmune disease. Clin Microbiol Rev. 2006;19:80–94
  94. Barak Y. The immune system and happiness. Autoimmun Rev. 2006;5:523–527
  95. Redman CW, Sargent IL. Placental debris, oxidative stress and pre-eclampsia. Placenta. 2000;21:597–602
  96. Benyo DF, Smarason A, Redman CW, Sims C, Conrad KP. Expression of inflammatory cytokines in placentas from women with preeclampsia. J Clin Endocrinol Metab. 2001;86(6):2505–2512
  97. Borzychowski AM, Sargent IL, Redman CW. Inflammation and pre-eclampsia. Semin Fetal Neonatal Med. 2006;11:309–316
  98. Schiessl B. Inflammatory response in preeclampsia. Mol Aspects Med. 2007;28(2):210–219
  99. Alexander BT, Cockrell K, Cline FD, Llinas MT, Sedeek M, Granger JP. Effect of angiotensin II synthesis blockade on the hypertensive response to chronic reductions in uterine perfusion pressure in pregnant rats. Hypertension. 2001;38(3 Pt 2):742–745
  100. Roberts L, LaMarca BB, Fournier L, Bain J, Cockrell K, Granger JP. Enhanced endothelin synthesis by endothelial cells exposed to sera from pregnant rats with decreased uterine perfusion. Hypertension. 2006;47(3):615–618
  101. Langer B, Grima M, Coquard C, Bader AM, Schlaeder G, Imbs JL. Plasma active renin, angiotensin I, and angiotensin II during pregnancy and in preeclampsia. Obstet Gynecol. 1998;91(2):196–202
  102. Brown MA, Zammit VC, Mitar DA, Whitworth JA. Renin-aldosterone relationships in pregnancy-induced hypertension. Am J Hypertens. 1992;5(6 Pt 1):366–371
  103. Roberts JM, Taylor RN, Musci TJ, Rodgers GM, Hubel CA, McLaughlin MK. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol. 1989;161(5):1200–1204
  104. Roberts JM, Edep ME, Goldfien A, Taylor RN. Sera from preeclamptic women specifically activate human umbilical vein endothelial cells in vitro: morphological and biochemical evidence. Am J Reprod Immunol. 1992;27(3–4):101–108
  105. Zhou CC, Zhang Y, Irani RA, Zhang H, Mi T, Popek EJ, et al. Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice. Nat Med, in press.

PII: S0143-4004(08)00202-6

doi: 10.1016/j.placenta.2008.06.011

Placenta
Volume 29, Issue 9 , Pages 763-771 , September 2008