FIGURE 4.

Schematic diagram illustrating angiogenesis induced by Cu²⁺/Co²⁺. Cu²⁺ enhances the angiogenic response by upregulating the expression of hypoxia-inducing-factor-1α (HIF-1α), thereby initiating the transcription of vascular endothelial growth factor (VEGF). Simultaneously, Co²⁺, acting as a prolyl hydroxylation inhibitor, inhibits the degradation of HIF-1α, maintaining its stability. The expression of HIF-1α and VEGF is induced in a dose-dependent manner, and the co-culture of HUVEC with Cu²⁺/Co²⁺ culture medium in vitro increases the expression of VEGF, platelet endothelial cell adhesion molecule (PECAM1), and HIF-1α-related genes in HUVEC. This enhancement significantly augments the ability of HUVEC to form tubular structures.