Targeted inhibition of complement activation prevents features of preeclampsia in mice

Kidney Int. 2011 Feb;79(3):331-9. doi: 10.1038/ki.2010.393. Epub 2010 Oct 13.


Preeclampsia is a major cause of maternal and neonatal morbidity and mortality. In mouse models, complement activation in the placenta is associated with abnormal placental development and miscarriage, and inhibiting complement prevents fetal injury. We mated two mouse strains, DBA/2 and CBA/J, expecting that the pregnancies might show features of preeclampsia and of immunologically mediated pregnancy loss. Along with placental dysfunction, these matings resulted in proteinuria, elevated BUN, fibrin deposition, and glomerular endotheliosis. We blocked placental complement activation throughout pregnancy by administering a single dose of the C3 inhibitor CR2-Crry given on day 5 of the pregnancy. This procedure specifically targets the sites of complement activation without inducing any systemic effects. Placental complement inhibition prevented oxidative stress and placental dysfunction, as well as proteinuria and renal pathologic features of preeclampsia. Thus, local blockade of complement activation at the maternal-fetal interface rescues preeclampsia in mice, and identifies new treatments. Hence, complement triggers a feed-forward cycle of placental damage, antiangiogenic factor production, and maternal vascular damage in patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Urea Nitrogen
  • Complement Activation / drug effects*
  • Disease Models, Animal
  • Female
  • Fibrin / metabolism
  • Injections, Intravenous
  • Kidney / drug effects*
  • Kidney / immunology
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / physiopathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Mice, Inbred DBA
  • Neovascularization, Physiologic / drug effects
  • Oxidative Stress / drug effects
  • Placenta / drug effects*
  • Placenta / immunology
  • Placenta / metabolism
  • Placenta / physiopathology
  • Pre-Eclampsia / drug therapy*
  • Pre-Eclampsia / immunology
  • Pre-Eclampsia / metabolism
  • Pre-Eclampsia / physiopathology
  • Pregnancy
  • Proteinuria / immunology
  • Proteinuria / prevention & control
  • Recombinant Fusion Proteins / administration & dosage*
  • Vascular Endothelial Growth Factor A / administration & dosage
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism


  • CR2-Crry fusion protein, mouse
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factor A
  • Fibrin
  • Flt1 protein, mouse
  • Vascular Endothelial Growth Factor Receptor-1