Signalling mechanisms of SDF-induced endothelial cell proliferation and migration

The aim of our study was to investigate the effect of stromal-derived factor-1-α (SDF-1-α) on endothelial angiogenic effects. SDF-1-α (50 ng/ml) increased the number of cultured endothelial cells from 33,653 ± 1183 to 55,398 ± 2741, which significantly reduced by adding the BKCa-inhibitor iberiotoxin, or the endothelial nitric oxide synthase-blocker, l-NMMA (n = 24, p < 0.05). Using the “Fences”-assay a significant increase of HUVEC migration induced by SDF-1-α was reported, which was blocked by the addition of iberiotoxin or l-NMMA (n = 12, p < 0.05). BKCa open-state probability (NPo) was analysed using the patch-clamp technique and NPo was increased from 0.003 (control) to 0.052 (SDF-1-α; n = 10, p < 0.05). NO synthesis was measured using a cGMP-radioimmunoassay. A significant increase of cGMP levels from 0.952 pmol/mg protein to 2.179 pmol/mg protein was observed, that was abolished by l-NMMA and significantly reduced by iberiotoxin (n = 15, p < 0.05). SDF-1-α increases endothelial proliferation and migration involving the activation of BKCa and an increased production of NO.