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 formation 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)) was similarly inhibited by 10 mu M 1-{beta-[3-(4-methoxyphenyl)propyl]-4-methoxyphenethyl}-H-imidazole hydrochloride (SKF 96365) and 10 mu M troglitazone. However, 10 mu M diltiazem had no effect. The basal tube formation obtained with 1% serum was augmented twofold by 100 ng/ml VEGF. SKF 96365 (0.1-10 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 endothelial cells was markedly inhibited by SKF 96365 but only slightly by troglitazone and diltiazem. The inhibition of tube formation by three Ca2+ entry blockers thus correlated with the inhibition of cell proliferation. The [Ca2+](i) elevation is thus not a prerequisite for VEGF to induce tube formation. (C) 2000 Elsevier Science B.V. All rights reserved.