Angiogenic stimuli are essential for survival of vascular endothelial cells in three-dimensional collagen lattice.
Cultured vascular endothelial cells derived from bovine aorta (BAECs) can survive and proliferate in the condition of two-dimensional monolayer culture in the presence of serum without any specific growth factors. When BAECs were embedded in collagen lattice, they underwent apoptotic death within 2 days unless the cultures were repeatedly supplied with angiogenic growth factor such as fibroblast growth factor-2 (FGF-2). Supplementation with FGF-2 induced endothelial cell differentiation, resulting in capillary-like tube formation inside collagen lattice. Following tube formation, withdrawal of FGF-2 induced disruption of the tube structures associated with the characteristic apoptotic cell death. These effects of FGF-2 were regulated by tyrosine phosphorylation, but not mediated through protein kinase C pathway. This model of endothelial cell apoptosis inside collagen lattice may represent in vivo endothelial cell-matrix interaction during angiogenesis process, indicating that apoptotic death of endothelial cells may regulate angiogenesis and the regression of vessels.
Satake
S
S
Department of Geriatrics, Nagoya University School of Medicine, Japan.
Kuzuya
M
M
Ramos
M A
MA
Kanda
S
S
Iguchi
A
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002196:Capillaries / Q000254:growth & development; D002417:Cattle; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D018919:Neovascularization, Physiologic
D016222:Fibroblast Growth Factor 2; D003094:Collagen