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2000
Volume 15, Issue 30
  • ISSN: 1381-6128
  • E-ISSN: 1873-4286

Abstract

Angiogenesis and inflammation are closely integrated processes. Fibroblast growth factor-2 (FGF2) is a prototypic angiogenesis inducer belonging to the family of the heparin-binding FGF growth factors. FGF2 exerts its proangiogenic activity by interacting with various endothelial cell surface receptors, including tyrosine kinase receptors, heparan-sulfate proteoglycans, and integrins. A tight cross-talk exists between FGF2 and the inflammatory response in the modulation of blood vessel growth. Pentraxins act as soluble pattern recognition receptors with a wide range of functions in various pathophysiological conditions. The long-pentraxin PTX3 shares the C-terminal pentraxin-domain with shortpentraxins and possesses a unique N-terminal domain. These structural features indicate that PTX3 may have distinct biological/ligand recognition properties when compared to short-pentraxins. Co-expression of PTX3 and FGF2 has been observed in different inflammation/angiogenesis-dependent diseases. PTX3 binds FGF2 with high affinity and specificity. The interaction prevents the binding of FGF2 to its cognate tyrosine kinase receptors, leading to inhibition of the angiogenic activity of the growth factor. This suggests that PTX3 may exert a modulatory function by limiting the angiogenic activity of FGF2. An integrated approach that utilized PTX3 fragments, monoclonal antibodies, and surface plasmon resonance analysis has identified the FGF2-binding domain in the unique N-terminal extension of PTX3. On this basis, PTX3-derived synthetic peptides have been designed endowed with a significant antiangiogenic activity in vitro and in vivo. They may provide the basis for the development of novel antiangiogenic FGF2 antagonists.

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/content/journals/cpd/10.2174/138161209789206962
2009-10-01
2025-05-10
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/content/journals/cpd/10.2174/138161209789206962
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  • Article Type:
    Research Article
Keyword(s): Angiogenesis; FGF2; innate immunity; modeling; NMR; pentraxin; synthetic peptides; tumor
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