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.