Inhibition of angiogenesis by two-chain high molecular weight kininogen (HKa) and kininogen-derived polypeptides

Can J Physiol Pharmacol. 2002 Feb;80(2):85-90. doi: 10.1139/y02-011.

Abstract

We recently reported that the two-chain form of human high molecular weight kininogen (HKa) inhibits angiogenesis by inducing endothelial cell apoptosis (Zhang et al. 2000). This property appears to be primarily conferred by HKa domain 5 (HKa D5). In this manuscript, we further characterize the activity of these polypeptides toward proliferating endothelial cells, as well as their in vivo anti-angiogenic activity in the chick chorioallantoic membrane (CAM). We also demonstrate that short peptides derived from endothelial cell binding regions in HKa domains 3 and 5 inhibit endothelial cell proliferation and induce endothelial cell apoptosis. Like HKa and HKa D5, peptides derived from the latter domain induce endothelial cell apoptosis in a Zn(2+)-dependent manner, while those derived from domain 3 function independently of Zn2+. The implications of these findings to the regulation of angiogenesis and development of anti-angiogenic therapeutics are discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Apoptosis / drug effects*
  • Cell Division / drug effects
  • Chick Embryo
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Humans
  • Kininogen, High-Molecular-Weight / chemistry
  • Kininogen, High-Molecular-Weight / pharmacology*
  • Peptide Fragments / pharmacology*
  • Zinc / pharmacology

Substances

  • Angiogenesis Inhibitors
  • HKa protein, human
  • Kininogen, High-Molecular-Weight
  • Peptide Fragments
  • Zinc