Dissociation between the Ca2+ signal and tube formation induced by vascular endothelial growth factor in bovine aortic endothelial cells

The correlation between the intracellular Ca2+ signal and the tube formatio n in collagen gels induced by vascular endothelial cell growth factor (VEGF ) was investigated using cultured bovine aortic endothelial cells. The VEGF -induced sustained elevation of cytosolic Ca2+ concentration ([Ca2+](i)) wa s similarly inhibited by 10 mu M 1-{beta-[3-(4-methoxyphenyl)propyl]-4-meth oxyphenethyl}-H-imidazole hydrochloride (SKF 96365) and 10 mu M troglitazon e. However, 10 mu M diltiazem had no effect. The basal tube formation obtai ned with 1% serum was augmented twofold by 100 ng/ml VEGF. SKF 96365 (0.1-1 0 mu M) inhibited the VEGF-induced and basal tube formation, while 10 mu M troglitazone or 10 mu M diltiazem had no effect. The proliferation of endot helial cells was markedly inhibited by SKF 96365 but only slightly by trogl itazone and diltiazem. The inhibition of tube formation by three Ca2+ entry blockers thus correlated with the inhibition of cell proliferation. The [C a2+](i) elevation is thus not a prerequisite for VEGF to induce tube format ion. (C) 2000 Elsevier Science B.V. All rights reserved.