Blocking angiogenesis with peptides that inhibit the activity of procollagen C-endopeptidase.
Journal Title: Pharmacological Reports - Year 2009, Vol 61, Issue 3
Abstract
Procollagen C-endopeptidase (BMP-1) is one of two key enzymes crucial for conversion of fibrillar procollagens to self-assembling collagen monomers. Recently, we have reported inhibition of the largest variant of BMP-1, a recombinant mammalian tolloid (mTld) in vitro, on procollagen type I using peptides with amino acid sequences in chordin conserved across different species. Here, we tested the same peptides as potent blockers of angiogenesis ex vivo in cultured rings of rat aorta, in vivo in chick embryos, and in vitro in cell cultures. Our results revealed that the peptides inhibited the angiogenic activity in rat aorta explants at micromolar concentrations; they also blocked blood vessel growth in chick embryos. The peptides were also tested on three types of human cells, e.g., umbilical vein endothelium, skin fibroblasts, and tumor HT-1080 cells. Since the three types of cells proliferated at a significantly lower rate or did not proliferate at all, we conclude that the anti-angiogenic effect observed in rat aorta ring explants and in chick embryos was related to inhibition of cell proliferation. In conclusion, we showed the ability to inhibit angiogenesis by blocking the activity of procollagen C-endopeptidase. The results strongly indicate crucial role(s) of this metalloproteinase in the formation of new blood vessels and maintenance of their growth.
Authors and Affiliations
Marta Lesiak, Aleksandra Auguściak-Duma, Anna Szydło, Aleksander Sieroń
Keywords
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