MODULATION OF CELL-MIGRATION AND VESSEL FORMATION BY VASCULAR ENDOTHELIAL GROWTH-FACTOR AND BASIC FIBROBLAST GROWTH-FACTOR IN CULTURED EMBRYONIC HEART

Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) stimulate endothelial cell proliferation, migration, and vascular tube formation. We tested the hypotheses that these growth f actors stimulate (1) cell migration and (2) assembly into cordlike str uctures in embryonic rat heart explants cultured on collagen gels, Atr ial and ventricular explants from rat embryos at 12 (E12, avascular) a nd 14 (E14, early vascularization stage) days of gestation were cultur ed on a collagen substrate, Western blot analysis of the explants indi cated that endogenous VEGF was present in both atria and ventricles du ring incubation. Addition of bFGF to E12 explants markedly increased c ell migration, whereas VEGF had no significant effect. In E14 explants neither growth factor influenced cell migration. Cotreatment with VEG F and bFGF did not have a synergistic effect on the migration distance of cells from either E12 or E14 embryonic hearts, However, VEGF stimu lated the appearance of cord-like structures in E14, but not E12, expl ants. Transmission electron microscopy analysis showed that these cord -like structures consist of elongated cells, some of which aggregate i nto clusters, or form tube-like structures, similar to capillaries, Se rial sections of monolayers revealed that tube formation occurs beneat h the surface of collagen gel. We conclude that in this model system V EGF and bFGF play distinct roles, at specific time points, in coronary vascular tube formation in the developing heart. (C) 1995 Wiley-Liss, Inc.