Basement Membrane Collagen: Degradation by Migrating Endothelial Cells

One of the first steps in neovascularization is dissolution of the basement membrane at the point of endothelial outgrowth. An assay was developed to determine whether basement membrane collagens (types IV and V) are degraded by endothelial cells migrating toward a chemotactic stimulus. Fetal bovine endothelial cells were placed on one side of a filter containing the collagen substrate, and a chemoattractant derived from retinal extracts was placed on the opposite side. Degradation of both type IV and type V collagens was observed when the retinal factor was placed on the side of the filter opposite the endothelial cells. Metalloproteinases that cleaved type IV and type V collagens could be extracted from the endothelial cells with detergents. Such endothelial cell-associated (possibly membrane-bound) proteinases may locally disrupt the basement membrane and facilitate the outgrowth of capillary sprouts toward the angiogenic stimulus.