title: Vascular endothelial cell migration in vitro roles of cyclic nucleotides, calcium ion and cytoskeletal system.
abstract: According to the response to injury hypothesis, endothelial migration and repair may play an important role in the initiation and progression of atherosclerosis. In this study, we examined the regulatory mechanisms of endothelial cell migration in vitro, using cultured endothelial cells from fetal bovine aortas. Dibutyryl cyclic AMP, 8-bromo cyclic GMP, and theophylline (each at concentrations of 10(-4) to 10(-3) M) inhibited the migration of endothelial cells. Migration was not significantly affected by the Ca2+ channel blockers diltiazem (10(-6) to 10(-4) M) and nicardipine (10(-6) to 10(-5) M) or by La3+ (10(-4) to 10(-3) M), an inorganic Ca2+-antagonist, TMB-8 (10(-6) to 5 x 10(-5) M), an intracellular Ca2+ blocker, or the calmodulin inhibitors W-7 (10(-6) to 5 x 10(-5) M) and trifluoperazine (10(-7) to 10(-5) M). At the extracellular Ca2+ concentrations of less than 0.2 mEq/l, the migration was inhibited significantly. In addition, migration was markedly suppressed by colchicine (10(-8) to 10(-5) M), an inhibitor of tubulin polymerization, and by cytochalasin B (10(-7) to 10(-5) M), an inhibitor of actin polymerization. These results suggest that cyclic nucleotides, such as cyclic AMP and GMP, may regulate the migration of vascular endothelial cells. Although a low concentration of extracellular Ca2+ is essential to their migration, participation of the intracellular Ca2+-calmodulin system was not evident in this study. It appears that the cytoskeletal system, including microtubules and microfilaments, is involved in the mechanisms of migration.
authors.affiliation: Department of Geriatrics, Nagoya University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Naito
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Kuzuya
authors.forename: C
authors.initials: C
authors.lastname: Funaki
authors.forename: K
authors.initials: K
authors.lastname: Asai
authors.forename: F
authors.initials: F
authors.lastname: Kuzuya
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic; D003994:Bucladesine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003078:Colchicine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000166:cytology*; D005333:Fetus; D005707:Gallic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D009529:Nicardipine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D013449:Sulfonamides; D014268:Trifluoperazine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003571:Cytochalasin B; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D003994:Bucladesine; C017967:W 7; D013806:Theophylline; D009529:Nicardipine; D004110:Diltiazem; D003078:Colchicine