Current Hypertension Reports

, Volume 9, Issue 2, pp 128–132

Agonist autoantibodies against the angiotensin AT1 receptor in renal and hypertensive disorders



Previous studies demonstrated the significance of an agonistic angiotensin II receptor AT1 autoantibody (AT1-AA) in preeclampsia. Because of its ability to release calcium in vascular smooth muscle cells, stimulate reactive oxygen species, and initiate proinflammatory processes, this antibody was thought to be important in the etiology and pathogenesis of preeclampsia. Recent investigations, however, have broadened and refined the pathobiological relevance of this antibody and refuted its role as the primary cause for preeclampsia. Because AT1-AA has been linked to an impaired uteroplacental perfusion and has been detected in patients with renal allograft rejection, its occurrence and function seem to be wider and more complex. This review summarizes current knowledge about the generation, function, and clinical importance of AT1-AA.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Schiffrin EL, Touyz RM: Multiple actions of angiotensin II in hypertension: benefits of AT1 receptor blockade. J Am Coll Cardiol 2003, 42:911–913.PubMedCrossRefGoogle Scholar
  2. 2.
    Hunyady L, Turu G.: The role of the AT1 angiotensin receptor in cardiac hypertrophy: angiotensin II receptor or stretch sensor? Trends Endocrinol Metab 2004, 15:405–408.PubMedCrossRefGoogle Scholar
  3. 3.
    Maric C, Zheng W, Walther T: Interactions between angiotensin II and atrial natriuretic peptide in renomedullary interstitial cells: the role of neutral endopeptidase. Nephron Physiol 2006, 103:149–156.CrossRefGoogle Scholar
  4. 4.
    Cheng ZJ, Vapaatalo H, Mervaala E: Angiotensin II and vascular inflammation. Med Sci Monit 2005, 11:RA194–205.PubMedGoogle Scholar
  5. 5.
    Quitterer U, Lother H, Abdalla S: AT1 receptor heterodimers and angiotensin II responsiveness in preeclampsia. Semin Nephrol 2004, 24:115–119.PubMedCrossRefGoogle Scholar
  6. 6.
    Shah DM: The role of RAS in the pathogenesis of preeclampsia. Curr Hypertens Rep 2006, 8:144–52.PubMedGoogle Scholar
  7. 7.
    Saito T, Ishida J, Takimoto-Ohnishi E, et al.: An essential role for angiotensin II type 1a receptor in pregnancy-associated hypertension with intrauterine growth retardation. FASEB J 2004, 18:388–390.PubMedGoogle Scholar
  8. 8.
    Wallukat G, Homuth V, Fischer T, et al.: Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor. J Clin Invest 1999, 103:945–952.PubMedGoogle Scholar
  9. 9.
    Thway TM, Shlykov SG, Day MC, et al.: Antibodies from preeclamptic patients stimulate increased intracellular Ca2+ mobilization through angiotensin receptor activation. Circulation 2004, 110:1612–1619.PubMedCrossRefGoogle Scholar
  10. 10.
    Sankaralingam S, Arenas IA, Lalu MM, Davidge ST: Preeclampsia: current understanding of the molecular basis of vascular dysfunction. Expert Rev Mol Med 2006, 8:1–20.PubMedCrossRefGoogle Scholar
  11. 11.
    Xia Y, Wen HY, Kellems RE: Angiotensin II inhibits human trophoblast invasion through AT1 receptor activation. J Biol Chem 2002, 277:24601–24608.PubMedCrossRefGoogle Scholar
  12. 12.
    Xia Y, Wen H, Bobst S, et al.: Maternal autoantibodies from preeclamptic patients activate angiotensin receptors on human trophoblast cells. J Soc Gynecol Investig 2003, 10:82–93.PubMedCrossRefGoogle Scholar
  13. 13.
    Dechend R, Gratze P, Wallukat G, et al.: Agonistic autoantibodies to the AT1 receptor in a transgenic rat model of preeclampsia. Hypertension 2005, 45:742–746.PubMedCrossRefGoogle Scholar
  14. 14.
    Verlohren S, Herse F, Pijnenborg R, et al.: Agonistic autoantibodies to the AT1 receptor in rat models of preeclampsia: induced by chronic reductions in uterine perfusion pressure (RUPP) and low dose TNFalpha infusion. Geburtsh Frauenheilk 2006, 66(Suppl 1):186.Google Scholar
  15. 15.
    Dragun D, Müller DN, Brasen JH, et al.: Angiotensin II type 1-receptor activating antibodies in renal-allograft rejection. N Engl J Med 2005, 352:558–569.PubMedCrossRefGoogle Scholar
  16. 16.
    Sibai B, Dekker G, Kupferminc M: Pre-eclampsia. Lancet 2005, 365:785–799.PubMedGoogle Scholar
  17. 17.
    Davison JM, Homuth V, Jeyabalan A, et al.: New aspects in the pathophysiology of preeclampsia. J Am Soc Nephrol 2004, 9:2440–2448.CrossRefGoogle Scholar
  18. 18.
    Dechend R, Viedt C, Muller DN, et al.: AT1 receptor agonistic antibodies from preeclamptic patients stimulate NADPH oxidase. Circulation 2003, 107:1632–1639.PubMedCrossRefGoogle Scholar
  19. 19.
    Fischer T, Wallukat G, Schneider MP, et al.: HELLP syndrome in the 18th week of gestation in association with elevated angiotensin AT(1)-receptor autoantibodies. Eur J Obstet Gynecol Reprod Biol 2001, 97:255–257.PubMedCrossRefGoogle Scholar
  20. 20.
    Walther T, Wallukat G, Jank A, et al.: The angiotensin II AT1 receptor autoimmune antibody reflects fundamental alterations of the utero-placental vasculature. Hypertension 2005, 46:1275–1279.PubMedCrossRefGoogle Scholar
  21. 21.
    Chien PF, Arnott N, Gordon A, et al.: How usefu is uterine artery Doppler flow velocimetry in the prediction of preeclampsia, intrauterine growth retardation and perinatal death? An overview. Br J Obstet Gynaecol 2000, 107:196–208.Google Scholar
  22. 22.
    Stepan H, Heihoff-Klose A, Faber R: Reduced antioxidant capacity in second-trimester pregnancies with pathological uterine perfusion. Ultrasound Obstet Gynecol 2004, 23:579–583.PubMedCrossRefGoogle Scholar
  23. 23.
    Liao YH, Wei YM, Wang M, et al.: Autoantibodies against AT1-receptor and alpha1-adrenergic receptor in patients with hypertension. Hypertens Res 2002, 25:641–646.PubMedCrossRefGoogle Scholar
  24. 24.
    Fu ML, Herlitz H, Schulze W, et al.: Autoantibodies against the angiotensin receptor (AT1) in patients with hypertension. J Hypertens 2000, 18:945–953.PubMedCrossRefGoogle Scholar
  25. 25.
    Dragun D, Brasen JH, Schonemann C, et al.: Patients with steroid refractory acute vascular rejection develop agonistic antibodies targeting angiotensin II type 1 receptor. Transplant Proc 2003, 35:2104–2105.PubMedCrossRefGoogle Scholar
  26. 26.
    Oldstone MB: Molecular mimicry and immune-mediated diseases. FASEB J 1998, 12:1255–1265.PubMedGoogle Scholar
  27. 27.
    Vecchi ML, Radice A, Renda F, et al.: Anti-laminin auto antibodies in ANCA-associated vasculitis. Nephrol Dial Transplant 2000, 15:1600–1603.PubMedCrossRefGoogle Scholar
  28. 28.
    Allen J, Forman A, Maigaard S, et al.: Effect of endogenous vasoconstrictors on maternal intramyometrial and fetal stem villous arteries in pre-eclampsia. J Hypertens 1989, 7:529–36.PubMedCrossRefGoogle Scholar
  29. 29.
    Langer B, Grima M, Coquard C, et al.: Plasma active renin, angiotensin I, and angiotensin II during pregnancy and in preeclampsia. Obstet Gynecol 1998, 91:196–202.PubMedCrossRefGoogle Scholar
  30. 30.
    AbdAlla S, Lother H, el Massiery A, Quitterer U: Increased AT(1) receptor heterodimers in preeclampsia mediate enhanced angiotensin II responsiveness. Nature Med 2001, 7:1003–1009.PubMedCrossRefGoogle Scholar
  31. 31.
    Rocheville M, Lange DC, Kumar U, et al.: Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity. Science 2000, 288:154–157.PubMedCrossRefGoogle Scholar
  32. 32.
    AbdAlla S, Lother H, Abdel-tawad AM, Quitterer U: The angiotensin II AT2 receptor is an AT1 receptor antagonist. J Biol Chem 2001, 276:39721–39726.PubMedCrossRefGoogle Scholar
  33. 33.
    Kostenis E, Milligan G, Christopoulos A, et al.: The G protein-coupled receptor Mas is a physiological antagonist of the angiotensin II AT1 receptor. Circulation 2005, 111:1806–1813.PubMedCrossRefGoogle Scholar
  34. 34.
    Stepan H, Wallukat G, Schultheiss HP, et al.: Is the parvovirus B19 the cause for autoimmunity against the angiotensin II type 1 receptor? J Reprod Immunol 2006, December 4, Epub ahead of print.Google Scholar
  35. 35.
    Momoeda M, Wong S, Kawase M, et al.: A putative nucleoside triphosphate-binding domain in the nonstructural protein of B19 parvovirus is required for cytotoxicity. J Virol 1994, 68:8443–8446.PubMedGoogle Scholar
  36. 36.
    Brown KE, Young NS: Parvovirus B19 in human disease. Annu Rev Med 1997, 48:59–67.PubMedCrossRefGoogle Scholar
  37. 37.
    Cohen BJ, Buckley MM: The prevalence of antibody to human parvovirus B19 in England and Wales. J Med Microbiol 1988, 25:151–153.PubMedCrossRefGoogle Scholar
  38. 38.
    Tschöpe C, Bock CT, Kasner M, et al.: High prevalence of cardiac parvovirus B19 infection in patients with isolated left ventricular diastolic dysfunction. Circulation 2005, 111:879–886.PubMedCrossRefGoogle Scholar
  39. 39.
    Vallbracht KB, Schwimmbeck PL, Kuhl U, et al.: Endothelium-dependent flow-mediated vasodilation of systemic arteries is impaired in patients with myocardial virus persistence. Circulation 2004, 110:2938–2945.PubMedCrossRefGoogle Scholar
  40. 40.
    Yeh SP, Chiu CF, Lee CC, et al.: Evidence of parvovirus B19 infection in patients of pre-eclampsia and eclampsia with dyserythropoietic anemia. Br J Haematol 2004, 126:428–433.PubMedCrossRefGoogle Scholar
  41. 41.
    Zaki M, Greenwood C, Redman CW, et al.: The spontaneous reversal of pre-eclampsia associated with parvovirus-induced hydrops and the placental theory of pre-eclampsia: a case report. Br J Obstet Gynecol 2003, 110:1125–1126.Google Scholar
  42. 42.
    Stepan H, Faber R: Elevated sFlt1 level and preeclampsia in a woman with parvo-virus-induced hydrops. N Engl J Med 2006, 354:1857–1858.PubMedCrossRefGoogle Scholar

Copyright information

© Current Medicine Group LLC 2007

Authors and Affiliations

  1. 1.Department of Cardiology and PneumologyCharité, Campus Benjamin FranklinBerlinGermany

Personalised recommendations