Dissociation between the Ca(2+) signal and tube formation induced by vascular endothelial growth factor in bovine aortic endothelial cells.
The correlation between the intracellular Ca(2+) 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 Ca(2+) concentration ([Ca(2+)](i)) was similarly inhibited by 10 microM 1-¿beta-[3-(4-methoxyphenyl)propyl]-4-methoxyphenethyl¿-1H-imidazole hydrochloride (SKF 96365) and 10 microM troglitazone. However, 10 microM 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 microM) inhibited the VEGF-induced and basal tube formation, while 10 microM troglitazone or 10 microM 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 Ca(2+) entry blockers thus correlated with the inhibition of cell proliferation. The [Ca(2+)](i) elevation is thus not a prerequisite for VEGF to induce tube formation.
Kawasaki
J
J
Department of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan.
Hirano
K
K
Hirano
M
M
Nishimura
J
J
Nakatsuka
A
A
Fujishima
M
M
Kanaide
H
H
D000818:Animals; D001011:Aorta / Q000166:cytology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D003094:Collagen; D004110:Diltiazem / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005782:Gels; D007093:Imidazoles / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D000077288:Troglitazone; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D002121:Calcium Channel Blockers; D002839:Chromans; D016228:Endothelial Growth Factors; D005782:Gels; D007093:Imidazoles; D008222:Lymphokines; D013844:Thiazoles; D045162:Thiazolidinediones; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D003094:Collagen; D004110:Diltiazem; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D000077288:Troglitazone; D002118:Calcium