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

Jing Chuan Zhang, Xiaoping Qi, Jose Juarez, Marian Plunkett, Fernando Donaté, Ramasamy Sakthivel, Andrew P. Mazar, Keith R. McCrae*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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 Zn2+-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.

Original languageEnglish (US)
Pages (from-to)85-90
Number of pages6
JournalCanadian Journal of Physiology and Pharmacology
Volume80
Issue number2
DOIs
StatePublished - 2002

Keywords

  • Angiogenesis
  • Apoptosis
  • Endothelial cells
  • Kininogen
  • Peptides

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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