HYPOXIA INDUCES CAPILLARY NETWORK FORMATION IN CULTURED BOVINE PULMONARY MICROVESSEL ENDOTHELIAL-CELLS

The development of new vessels (angiogenesis) is essential to wound he aling. The center of a wound space is hypoxic, a condition that has be en shown to stimulate angiogenesis in animal models of coronary artery occlusion. Because the mechanisms involved in this complex process ar e difficult to study in situ, an in vitro model would provide a useful complement to in vivo studies. This laboratory has developed and char acterized calf pulmonary microvessel endothelial cell (PMVEC) cultures and an in vitro model system of angiogenesis using collagen three-dim ensional gels that permit migration of cells into vessel networks. Thi s system was used to study the direct effect of normoxia (20% O-2) or hypoxia (5% O-2) on PMVEC ability to undergo angiogenesis in vitro. Ma jor changes leading to formation of capillary-like networks occurred d uring the first 3 days of hypoxic exposure only and included restructu ring of actin filament networks, focal changes in distribution of basi c fibroblast growth factor, and orientation and migration of cell trac ts into a collagen gel matrix to form vessel networks.