Adhesion inhibition "in vitro" by heparin derivatives correlates with their activity on angiogenesis in mice.
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.
Rizea Savu
Simona
S
National Institute for Pharmaceutical Chemistry, 112 Vitan Rd., Bucharest, Romania. Dreispharma@aol.com
Silvestro
L
L
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology*; D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D006493:Heparin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007797:Laminin / Q000378:metabolism; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D006493:Heparin; D003094:Collagen