Transcriptional activity of the alpha 1(I)-collagen promoter is correlated with the formation of capillary-like structures by endothelial cells in vitro.

ABSTRACT

Bovine aortic endothelial (BAE) cells spontaneously form structures in vitro that resemble capillary-like cords or tubes. This process is associated with changes in the expression of certain extracellular matrix proteins that include type I collagen. BAE cells exhibiting angiogenesis in vitro were transfected with plasmids containing either chloramphenicol acetyltransferase or human growth hormone genes directed by promoter sequences from the human alpha 1(I)-collagen gene. Immunostaining for chloramphenicol acetyltransferase demonstrated that collagen promoter activity was restricted to cells involved in the formation of endothelial cords. In comparison to transfected monolayers of BAE cells, the transcriptional activity of the alpha 1(I)-collagen promoter increased by 7-fold in cultures undergoing angiogenesis in vitro. The selective ability of angiogenic endothelium to utilize the alpha 1(I)-collagen promoter is consistent with previous studies showing high levels of alpha 1(I)-collagen mRNA in BAE cells actively engaged in the formation of tubes (Iruela-Arispe, L., Hasselaar, P., and Sage, H. (1991) Lab. Invest. 64, 174-186). We conclude that transcriptional activation of the alpha 1(I)-collagen gene is closely linked to the morphologic alterations in cellular phenotype that accompany the transition of quiescent endothelial monolayers to the angiogenic state.