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Bone morphogenetic protein-9 is a circulating vascular quiescence factor.

Laurent David1, Christine Mallet, Michelle Keramidas

  • 1Institut National de la Santé et de la Recherche Médicale, U878, Grenoble, France.

Circulation Research
|March 1, 2008
PubMed
Summary

Bone morphogenetic protein (BMP)9 is a circulating anti-angiogenic factor. It circulates at biologically active concentrations and inhibits endothelial cell migration and growth, suggesting a role in vascular quiescence.

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Area of Science:

  • Vascular biology
  • Endocrinology

Background:

  • Angiogenesis is regulated by stimulatory and inhibitory signals.
  • Activin receptor like-kinase 1 (ALK1) is an endothelial cell receptor involved in angiogenesis.
  • Mutations in ALK1 cause hereditary hemorrhagic telangiectasia type 2 (HHT2).

Purpose of the Study:

  • To investigate the role of bone morphogenetic protein (BMP)9 and BMP10 in vascular quiescence.
  • To determine if BMP9 circulates in human serum at biologically active concentrations.
  • To assess the anti-angiogenic effects of BMP9 in vivo.

Main Methods:

  • Detection of BMP9 in human serum using neutralizing antibodies.
  • Quantification of circulating BMP9 levels.
  • Assessment of BMP9's effect on angiogenesis using mouse sponge and chicken chorioallantoic membrane assays.

Main Results:

  • Human serum induced Smad1/5 phosphorylation, which was inhibited by anti-BMP9 antibodies.
  • BMP9 circulates in healthy humans at concentrations (2-12 ng/mL) above its EC(50) (50 pg/mL).
  • BMP9 significantly inhibited sprouting angiogenesis in vivo and blood circulation in a chicken model.

Conclusions:

  • BMP9 is a circulating, biologically active anti-angiogenic factor.
  • BMP9 likely plays a physiological role in maintaining adult blood vessel quiescence.
  • BMP9 represents a potential therapeutic target for angiogenesis-related disorders.