on May 6, 2004
Published online before print May 6, 2004, doi: 10.1161/01.ATV.0000130663.37663.6a
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Submitted on March 25, 2004
Accepted on April 21, 2004
Basic Fibroblast Growth Factor-Induced Endothelial Proliferation and NO Synthesis Involves Inward Rectifier K+ Current
Wolfram Scharbrodt ;
From the Department of Cardiology and Angiology (W.S., C.R.W.K., Y.W., C.A.S., A.K.M., U.B., T.N., H.T., B.W., A.E.), Justus-Liebig-University of Giessen, Germany; and the Department of Internal Medicine (J.W.), Hospital Bad Orb, Germany.
* To whom correspondence should be addressed. E-mail: Christoph.R.Kuhlmann{at}innere.med.uni-giessen.de.
Objectives--Inward rectifier K+ currents (Kir) determine the resting membrane potential and thereby modulate essential Ca2+-dependent pathways, like cell growth and synthesis of vasoactive agents in endothelial cells. Basic fibroblast growth factor (bFGF) acts as a vasodilatator and angiogenic factor. Therefore, we investigated the effect of bFGF on Kir and assessed the role in proliferation and nitric oxide (NO) formation of endothelial cells.
Methods and Results--Using the patch-clamp technique, we found characteristic Kir in human umbilical cord vein endothelial cells (HUVEC), which were dose-dependently blocked by barium (10 to 100 µmol/L). Perfusion with bFGF (50 ng/mL) caused a significant increase of Kir, which was blocked by 100 µmol/L barium (n=18, P<0.01). The bFGF-induced HUVEC proliferation was significantly inhibited when using 50 to 100 µmol/L barium (n=6; P<0.01). NO production was examined using a cGMP radioimmunoassay. bFGF caused a significant increase of cGMP levels (n=10; P<0.05), which were blocked by barium.
Conclusions--Modulation of Kir plays an important role in bFGF-mediated endothelial cell growth and NO formation.
Key words: growth factors • ion channels • angiogenesis • nitric oxide