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  • Title: Suramin is a potent inhibitor of vascular endothelial growth factor. A contribution to the molecular basis of its antiangiogenic action.
    Author: Waltenberger J, Mayr U, Frank H, Hombach V.
    Journal: J Mol Cell Cardiol; 1996 Jul; 28(7):1523-9. PubMed ID: 8841939.
    Abstract:
    Vascular Endothelial Growth Factor (VEGF) is a specific endothelial mitogen and an important angiogenic factor in vivo, capable of inducing therapeutic angiogenesis when administered to ischemic myocardium. Suramin, originally developed as an anti-trypanosomal agent, was recently shown to exert an antiangiogenic action. We have tested the hypothesis, whether the antiangiogenic effect of suramin may be mediated via inhibition of VEGF function. Using cultured endothelial cells and a [3H]thymidine incorporation assay we were able to show, that the action of VEGF upon mitogenicity is inhibited by suramin in a dose-dependent manner. The same was true for inhibition of VEGF-induced chemotaxis of endothelial cells. Suramin inhibited VEGF-inducible tyrosine phosphorylation of KDR as determined by in vitro kinase assay. Moreover, suramin was shown to inhibit VEGF-induced tyrosine phosphorylation of KDR in intact cells, indicating an interaction of suramin with the VEGF-receptor KDR as the cause of its inhibitory activity. The antiangiogenic effect of suramin may be mediated-at least in part-by inhibition of VEGF function. Given the feasibility of in vivo use, suramin may be a valuable tool for investigating the functional role of angiogenesis in the cardiovascular system.
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