[Evidence for a major role of Mg2+ in VEGF165-mediated angiogenesis].
OBJECTIVE
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.


METHODS
[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+).


RESULTS
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.


CONCLUSIONS
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.
Hong
Bing-zhe
BZ
Department of Cardiology, Xinhua Hospital, Dalian University Medical School, Dalian 116021, China.
Piao
Hai-nan
HN
Li
Sheng-fan
SF
Piao
Hua
H
Jin
Long
L
Cao
Ping-an
PA
D002413:Cations, Divalent; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008274:Magnesium / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D002413:Cations, Divalent; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D008274:Magnesium