title: Recombinant vascular endothelial growth factor 121 attenuates autoantibody-induced features of pre-eclampsia in pregnant mice.
abstract: BACKGROUND
  Pre-eclampsia (PE) is a serious hypertensive disorder of pregnancy characterized by excessive production of a soluble form of the vascular endothelial growth factor (VEGF) receptor-1, termed soluble fms-like tyrosine kinase-1 (sFlt-1). This placental-derived factor is believed to be a key contributor to the clinical features of PE. Women with PE are also characterized by the presence of autoantibodies, termed angiotensin type 1 receptor activating autoantibody (AT(1)-AA), that activate the major angiotensin receptor, AT(1). These autoantibodies cause clinical features of PE and elevated sFlt-1 when injected into pregnant mice. The research reported here used this autoantibody-injection model of PE to assess the therapeutic potential of recombinant VEGF(121), a relatively stable form of the natural ligand.
  
  
  METHODS
  Immunoglobulin G (IgG) from women with PE was injected into pregnant mice with or without continuous infusion of recombinant VEGF(121). Injected mice were monitored for symptoms of PE.
  
  
  RESULTS
  As a result of infusion of recombinant VEGF(121) autoantibody-induced hypertension (systolic blood pressure) was reduced from 159 ± 5 to 124 ± 5 mm Hg, proteinuria from 111 ± 16 to 40 ± 5 mg protein/mg creatinine and blood urea nitrogen levels from 31 ± 1 mg/dl to 18 ± 2 mg/dl, P < 0.05. Histological analysis revealed that autoantibody-induced glomerular damage including the narrowing of Bowman's space and occlusion of capillary loop spaces was largely prevented by VEGF(121) infusion. Finally, impaired placental angiogenesis resulting from AT(1)-AA injection was significantly improved by VEGF(121) infusion.
  
  
  CONCLUSIONS
  The infusion of recombinant VEGF(121) significantly attenuated autoantibody-induced features of PE.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, USA.
authors.forename: Athar H
authors.initials: AH
authors.lastname: Siddiqui
authors.forename: Roxanna A
authors.initials: RA
authors.lastname: Irani
authors.forename: Yujin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Dai
authors.forename: Sean C
authors.initials: SC
authors.lastname: Blackwell
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ramin
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Kellems
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D001323:Autoantibodies / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D007668:Kidney / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010920:Placenta / Q000098:blood supply / Q000473:pathology; D011225:Pre-Eclampsia / Q000188:drug therapy*; D011247:Pregnancy; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*
chemical_list: D018952:Antigens, CD34; D001323:Autoantibodies; D044140:Receptor, Angiotensin, Type 1; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A