Abstract 16460: Insulin-Like Growth Factor Binding Protein-2: A Putative Agent for Therapeutic Angiogenesis Acting via Its Arginine-Glycine-Aspartic Acid (RGD) Domain

Therapeutic angiogenesis is under investigation to restore tissue perfusion in ischaemic heart disease and peripheral arterial disease. Insulin-like growth factor binding protein-2 (IGFBP-2) has been attributed with pro-angiogenic activity but the molecular mechanisms have not been established. Structurally, IGFBP-2 possesses insulin-like growth factor (IGF) binding-, integrin recognition- (Arginine-Glycine-Aspartic Acid (RGD)) and heparin binding- sites and a nuclear localisation signal which may be implicated in its cellular actions. We hypothesise that IGFBP-2 can be exploited to promote therapeutic angiogenesis through cellular actions mediated by one or more of its structural domains. Restoration of limb perfusion was quantified by laser Doppler imaging following hind limb ischemia in mice expressing human IGFBP-2. Mechanistic studies were carried out in cultured human umbilical vein endothelial cells (HUVEC). Functional angiogenic responses were explored with tube formation and cell adhesion assays....