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

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 acti...

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Published in:Canadian journal of physiology and pharmacology 2002-02, Vol.80 (2), p.85-90
Main Authors: Zhang, Jing-Chuan, Qi, Xiaoping, Juarez, Jose', Plunkett, Marian, Donaté, Fernando, Sakthivel, Ramasamy, Mazar, Andrew P, McCrae, Keith R
Format: Article
Language:English
Subjects:
Angiogenesis Inhibitors - pharmacology
Animals
Apoptosis - drug effects
Biological and medical sciences
Blood vessels and receptors
Cell Division - drug effects
Chick Embryo
Endothelium, Vascular - cytology
Endothelium, Vascular - drug effects
Fibroblasts - cytology
Fibroblasts - drug effects
Fundamental and applied biological sciences. Psychology
Humans
Kininogen, High-Molecular-Weight - chemistry
Kininogen, High-Molecular-Weight - pharmacology
Peptide Fragments - pharmacology
Vertebrates: cardiovascular system
Zinc - pharmacology
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Summary: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 Zn 2+ . The implications of these findings to the regulation of angiogenesis and development of anti-angiogenic therapeutics are discussed.Key words: angiogenesis, kininogen, endothelial cells, apoptosis, peptides.
ISSN:0008-4212
1205-7541
DOI:10.1139/y02-011