Elevated soluble Flt1 inhibits endothelial repair in PR3-ANCA-associated vasculitis

J Am Soc Nephrol. 2012 Jan;23(1):155-64. doi: 10.1681/ASN.2010080858. Epub 2011 Oct 27.


Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis exhibits endothelial damage, but the capacity for vessel repair in this disorder is not well understood. Here, we observed a marked increase in serum levels of soluble Flt1 (sFlt1), a potent inhibitor of vascular endothelial growth factor, in patients with active ANCA-associated vasculitis compared with patients during remission and other controls. Serum levels of sFlt1 correlated with C5a, an anaphylatoxin released after complement activation. Serum from patients with acute ANCA-associated vasculitis disrupted blood flow in the chicken chorioallantoic membrane assay, suggesting an antiangiogenic effect. Preincubation with excess human vascular endothelial growth factor prevented this effect. Anti-proteinase-3 (PR3) mAb and serum containing PR3-ANCA from patients with active vasculitis both induced a significant and sustained release of sFlt1 from monocytes, whereas anti-myeloperoxidase (MPO) mAb or polyclonal antibodies did not. However, the serum containing polyclonal PR3-ANCA did not induce release of sFlt1 from cultured human umbilical vein endothelial cells. In summary, these data suggest that anti-PR3 antibodies, and to a much lesser extent anti-MPO antibodies, increase sFlt1 during acute ANCA-associated vasculitis, leading to an antiangiogenic state that hinders endothelial repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / blood*
  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / physiopathology
  • Case-Control Studies
  • Chick Embryo
  • Chorioallantoic Membrane
  • Complement C5a / metabolism
  • Endothelium, Vascular / physiopathology*
  • Humans
  • Monocytes / metabolism
  • Myeloblastin / immunology
  • Neovascularization, Physiologic*
  • Protein Isoforms / metabolism
  • Vascular Endothelial Growth Factor Receptor-1 / blood*
  • Vascular Endothelial Growth Factor Receptor-1 / metabolism


  • Protein Isoforms
  • Complement C5a
  • FLT1 protein, human
  • Vascular Endothelial Growth Factor Receptor-1
  • Myeloblastin