Vascular endothelial growth factor increases the intracellular magnesium

Vascular endothelial growth factor (VEGF) is one of the key players in the process of angiogenesis. However, its underlying mechanism remains unclear. Mg²⁺ is the most abundant intracellular divalent cation in the body and plays critical roles in many cell functions. We investigated the effect of VEGF on intracellular Mg²⁺ in human umbilical vein endothelial cells (HUVECs). VEGF-A₁₆₅ increased the intracellular Mg²⁺ concentration ([Mg²⁺]_i) in a dose-dependent manner, with or without extracellular Mg²⁺, and the increase of [Mg²⁺]_i was blocked by pretreatment with SU1498, tyrosine kinase inhibitors (tyrphostin A-23 and genistein), phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) or phospholipase Cγ (PLCγ) inhibitor (U73122). In contrast, mitogen-activated protein kinase inhibitors (SB202190 and PD98059) had no effect on the VEGF-induced [Mg²⁺]_i increase. These results suggest that VEGF-A₁₆₅ increases the [Mg²⁺]_i from the intracellular Mg²⁺ stores through the tyrosine kinase/PI3K/PLCγ-dependent signaling pathways.