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-alpha (SDF-1-alpha) on endothelial angiogenic effects. SDF-1-alpha (50 ng/ml) increased the number of cultured endothelial cells from 33,653 +/- 1183 to 55,398 +/- 2741, which significantly reduced by adding the BK(Ca)-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-alpha was reported, which was blocked by the addition of iberiotoxin or L-NMMA (n = 12, p < 0.05). BK(Ca) open-state probability (NPo) was analysed using the patch-clamp technique and NPo was increased from 0.003 (control) to 0.052 (SDF-1-alpha; 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-alpha increases endothelial proliferation and migration involving the activation of BK(Ca) and an increased production of NO.
Kuhlmann
Christoph Rüdiger Wolfram
CR
Justus-Liebig-University of Giessen, Department of Cardiology and Angiology, Germany. Chr_Kuhlmann@web.de
Schaefer
Christian Alexander
CA
Reinhold
Lars
L
Tillmanns
Harald
H
Erdogan
Ali
A
D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009569:Nitric Oxide / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D009569:Nitric Oxide