VEGF165-induced angiogenesis by regulating intracellular free Mg2+ in HUVECs / 中国应用生理学杂志

<p><b>AIM</b>The mechanism of vascular endothelial growth factor165 (VEGF165) on intracellular free magnesium ([Mg2+]i) in human umbilical vein endothelial cells (HUVECs) was investigated.</p><p><b>METHODS</b>[Mg2+]i in HUVECs loaded with fluorescent magnesium indicator mag-fura-2 were quantitatively detected the use of intracellular cation measurement system.</p><p><b>RESULTS</b>VEGF165 significantly increased [Mg2+]i in the extracellular Mg2+ and this effect could be blocked by pretreatment with tyrosine kinase inhibitors (tyrphostin A23 and genistein), phosphatidylinositol 3-kinase (PI3K) inhibitors (wortmannin and LY294002) and phospholipase Cgamma (PLCgamma) inhibitor (U73122). In contrast, phospholipase Cgamma (PLCgamma) inhibitor analog (U73343), mitogen-activated protein kinase inhibitors (SB202190 and PD98059) had no effect on the VEGF165-induced [Mg2+]i increase.</p><p><b>CONCLUSION</b>The increase of [Mg2+]i by VEGF165 originates from intracellular Mg2+ pool through tyrosine kinase/ PI3K/PLCgamma-dependent signaling pathways.</p>

Evidence for a major role of Mg2+ in VEGF165-mediated angiogenesis / 中华心血管病杂志

<p><b>OBJECTIVE</b>The effect of vascular endothelial growth factor(165) (VEGF(165)) on intracellular free magnesium ([Mg(2+)](i)) and the relationship between Mg(2+) and angiogenesis in human umbilical vein endothelial cells (HUVECs) were investigated in this study.</p><p><b>METHODS</b>[Mg(2+)](i) in HUVECs loaded with fluorescent magnesium indicator mag-fura-2 were quantitatively detected with the use of intracellular cation measurement system. HUVECs were obtained from normal fetus and cultured in M199 with 0.2 fetal bovine serum. The angiogenesis effects of VEGF(165) were observed in presence of 0 mmol/L, 1 mmol/L or 2 mmol/L of extracellular Mg(2+).</p><p><b>RESULTS</b>VEGF(165) significantly increased [Mg(2+)](i) in a dose-dependent manner independent of extracellular Mg(2+), Na(+) and Ca(2+) and this effect could be blocked by pretreatment with VEGF(165) receptor-2 (KDR) inhibitor (SU1498). The angiogenesis induced by VEGF(165) was significantly inhibited cells with 0 mmol/L extracellular Mg(2+), the angiogenesis effects of VEGF(165) were similar in cells with 1 mmol/L and 2 mmol/L extracellular Mg(2+) and these effects could be blocked by SU1498.</p><p><b>CONCLUSIONS</b>These results suggest that the [Mg(2+)](i) increase induced by VEGF(165) originates from intracellular Mg(2+) pools and promotes angiogenesis via KDR-dependent signaling pathways.</p>