Anti-angiogenic properties of ADAMTS-4 in vitro

Int J Exp Pathol. 2012 Feb;93(1):70-7. doi: 10.1111/j.1365-2613.2011.00802.x.


Angiogenesis is an indispensable mechanism in development and in many pathologies, including cancer, synovitis and aberrant wound healing. Many angiogenic stimulators and inhibitors have been investigated, and some have progressed to the clinic. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a group of multifunctional proteinases. ADAMTS-1 and ADAMTS-8 have been reported to be anti-angiogenic. Here, we provide evidence that ADAMTS-4, like ADAMTS-1, is expressed by endothelial cells and binds to vascular endothelial groth factor (VEGF). Moreover, ADAMTS-4 inhibited human dermal microvascular endothelial cells (HuDMEC) VEGF-stimulated VEGF receptor (R) R2 phosphorylation, differentiation and migration, suggesting that ADAMTS-4 may be a novel anti-angiogenic molecule.

MeSH terms

  • ADAM Proteins / metabolism*
  • ADAM Proteins / pharmacology*
  • ADAMTS1 Protein
  • ADAMTS4 Protein
  • Angiogenesis Inhibitors / metabolism*
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cells, Cultured
  • Dermis / blood supply
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism*
  • Humans
  • Phosphorylation / drug effects
  • Procollagen N-Endopeptidase / metabolism*
  • Procollagen N-Endopeptidase / pharmacology*
  • Umbilical Veins / cytology
  • Umbilical Veins / drug effects
  • Umbilical Veins / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor A / pharmacology
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism


  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factor Receptor-2
  • ADAM Proteins
  • ADAMTS1 Protein
  • ADAMTS1 protein, human
  • Procollagen N-Endopeptidase
  • ADAMTS4 Protein
  • ADAMTS4 protein, human