ANGIOGENIC STIMULI ARE ESSENTIAL FOR SURVIVAL OF VASCULAR ENDOTHELIAL-CELLS IN 3-DIMENSIONAL COLLAGEN LATTICE

Cultured vascular endothelial cells derived from bovine aorta (BAECs) can survive and proliferate in the condition of two-dimensional monola yer culture in the presence of serum without any specific growth facto rs. When BAECs were embedded in collagen lattice, they underwent apopt otic 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 differentiatio n, resulting in capillary-like tube formation inside collagen lattice. Following tube formation, withdrawal of FGF-2 induced disruption of t he tube structures associated with the characteristic apoptotic cell d eath. These effects of FGF-2 were regulated by tyrosine phosphorylatio n, but not mediated through protein kinase C pathway. This model of en dothelial cell apoptosis inside collagen lattice may represent in vivo endothelial cell-matrix interaction during angiogenesis process, indi cating that apoptotic death of endothelial cells may regulate angiogen esis and the regression of vessels. (C) 1998 Academic Press.