Abstract
Heparin (HEP) play an important role in angiogenesis. Inhibition of matrix degrading enzymes and binding to adhesion molecules are some of the interaction mechanism. The bleeding risk and the need of parenteral administration, restrict the therapeutic use of HEP as angiogenesis modulator, presently derivatives, with different pharmacokinetic and anticoagulant properties, are available. In this study the “in vitro” anti‐adhesion activity, tested with PMNs and endothelial cells, was compared with the effect on angiogenesis, evaluated in Matrigel implanted mice. Some HEP derivatives, with low anticoagulant activity, showed a significant angiogenesis inhibition. A positive correlation between adhesion inhibition in vitro and anti‐angiogenesis effect in vivo was found suggesting that the interaction with adhesion molecules by HEP derivatives play a relevant role in the angiogenesis control.
Keywords: angiogenesis, adhesion ‐heparin, sulphated glicosaminoglycan
References
- 1. Folkman J., Weisz P. B., Jonllie N. M., Liw W., Ewing W. R., Control of angiogenesis with synthetic heparin substitutes, Science, 243: 1490–1493, 1989. [DOI] [PubMed] [Google Scholar]
- 2. Benelli U., Bocci G., Danesi R., Lepri A., Bernardini M., Bianchi F., Lupetti M., Dolfi A., Campagni A., Agen C., Nardi M., Del Tacca M., The heparan sulphate suleparoide inhibits rat corneal angiogenesis and in vitro neovascularization, Exp. Eye Res., 67: 133–142, 1998. [DOI] [PubMed] [Google Scholar]
- 3. Silvestro L., Viano I., Macario M., Colangelo D., Montrucchio G., Panico S., Fantozzi R., Effects of heparin and its desulphated derivatives on leukocyte‐endothelial adhesion, Semin. Thromb. Hemost., 20: 254–258, 1994. [DOI] [PubMed] [Google Scholar]
- 4. Passaniti A., Taylor R. M., Pili R., Guo Y., Long P. U., Haney J. A., Pauly R. R., Grant D. S., Martin G. R., A simple quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basament membrane, heparin, and fibroblast growth factor, Lab. Invest., 67: 519–528, 1992. [PubMed] [Google Scholar]
- 5. Hahnenberger R., Jakobson A. M., Ansari A., Wehler T., Suahn C. N., Linhahl U., Low‐sulphated oligosaccharides derived from heparan sulphate inhibit normal angiogenesis, Glycobiology, 3: 567–573, 1993. [DOI] [PubMed] [Google Scholar]
- 6. Raab G., Klagsbrun M., Heparin‐binding EGF‐like growth factor. Biochim Biophys Acta, 1333: 179–199, 1997. [DOI] [PubMed] [Google Scholar]
