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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1229.)
© 2004 American Heart Association, Inc.

Vascular Biology

Basic Fibroblast Growth Factor–Induced Endothelial Proliferation and NO Synthesis Involves Inward Rectifier K⁺ Current

Wolfram Scharbrodt; Christoph Rüdiger Wolfram Kuhlmann; Yongijan Wu; Christian Alexander Schaefer; Astrid Kerstin Most; Ulrich Backenköhler; Thomas Neumann; Harald Tillmanns; Bernd Waldecker; Ali Erdogan; Johannes Wiecha

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.

Correspondence to Christoph Rüdiger Wolfram Kuhlmann, Justus-Liebig University Giessen, Department of Cardiology and Angiology, Klinikstr. 36, 35392 Giessen, Germany. E-mail Christoph.R.Kuhlmann{at}innere.med.uni-giessen.de

Objectives— Inward rectifier K⁺ currents (K_ir) 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 K_ir 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 K_ir 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 K_ir, 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 K_ir plays an important role in bFGF-mediated endothelial cell growth and NO formation.

The effect of bFGF on inward rectifier K⁺ currents (K_ir) was analyzed in HUVEC. bFGF caused an increase of K_ir, which was blocked by barium. Endothelial proliferation and NO production induced by bFGF were inhibited by reducing K_ir activity with barium.

Key Words: growth factors • ion channels • angiogenesis • nitric oxide