Blocking angiogenesis with peptides that inhibit the activity of procollagen C-endopeptidase.
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.
Lesiak
Marta
M
Department of General and Molecular Biology and Genetics, Centre of Excellence for Research and Teaching of Molecular Biology of Matrix and Nanotechnology, BioMedTech Silesia, Medical University of Silesia in Katowice, Medyków 18, Bldg C-1, PL 40-752 Katowice, Poland.
Auguściak-Duma
Aleksandra
A
Szydło
Anna
A
Sieroń
Aleksander L
AL
D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D055395:Bone Morphogenetic Protein 1 / Q000037:antagonists & inhibitors*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry*; D008297:Male; D008969:Molecular Sequence Data; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats
D020533:Angiogenesis Inhibitors; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010455:Peptides; C054234:chordin; D055395:Bone Morphogenetic Protein 1