Abstract: Aim To study the proliferative effect of hydroxysafflor yellow A (HSYA) on cultured canine aortic endothelial cell (VEC) in normoxic (21% O2) or hypoxic (10% O2) culture and the underlying mechanism. Methods The endothelial cells were scratched from trypsined canine aorta endothelium. HSYA was added to the cells at final concentrations of 1×10^-3, 1×10^-4 and 1×10^-5 mol·L^-1, respectively. VEGF (2.6×10^-7 mol·L^-1)-treated cells were used as the positive control. The proliferative effect of HSYA on VEC was determined at 48, 72, 96, and 120 h in normoxic culture by MTT assay. Similarly, the proliferation of VEC was determined at 12, 24, 48, and 72 h in hypoxic culture by MTT assay. The effects of HSYA on VEC proliferation and VEGF secretion were investigated by MTT and ELISA assays at the presence of the antibodies to VEGF and VEGF receptors. Results Pretreatment with HSYA at concentrations of 1×10^-3 and 1×10^-4 mol·L^-1 enhanced VEC proliferation in normoxic culture. The most significant enhancing effect of HSYA on VEC proliferation was achieved at 24, 48, and 72 h in hypoxic culture in concentration-dependent and time-dependent manner. HSYA at 1×10^-3 mol·L^-1 showed a potency similar to VEGF at 2.6×10^-7 mol·L^-1. Pretreatment with the antibodies of Flt-1, KDR or VEGF blocked the proliferative effect of HSYA with similar potencies. Antibodies of Flt-1 or VEGF antagonized the promoting effect of HSYA on VEGF secretion. Conclusion HSYA promotes VEC proliferation either in normoxic or hypoxic culture, especially in the latter condition. This effect of HSYA is at least partly mediated by VEGF and VEGF receptor.

Key words: hydroxysafflower yellow A, hydroxysafflower yellow A, endothelium, endothelium, angiogenesis, angiogenesis, vascular endothelial growth factor, vascular endothelial growth factor, hypoxia, hypoxia