The Role of Basement Membranes in Vascular Development

Endothelial cells produce and bind to multiple basement membrane components. Fibronectin and interstitial collagens seem to promote migration and proliferation, whereas basement membrane collagen and laminin stimulate attachment and differentiation. Human umbilical vein endothelial cells will rapidly form capillary-like structures when plated on a reconstituted basement membrane gel. This morphological differentiation involves the alignment of the cells followed by their close association with one another and the formation of a central lumen. Using antibodies to basement membrane components, we find that the formation of these vessels is a complex process involving multiple interactions with several matrix components. Synthetic peptides to active sequences in laminin have demonstrated that at least two sites in laminin participate in tube formation. An RGD-containing site on the A chain appears to mediate cell to matrix adhesion, and synthetic RGD-containing peptides block cell to matrix adhesion during tube formation. A YIGSR-containing site on the B1 chain appears to mediate cell to cell adhesion and promote tube formation because synthetic peptides block the strong cell interactions involved in tube formation. Our data with laminin peptides show that for at least one protein, multiple sites are recognized. Such data would also suggest that several cellular receptors are involved in a concerted process in laminin-induced differentiation of endothelial cells. We conclude that vessel formation is a complex, multistep process. Identification of active sites that block this process may have potential use in blocking angiogenesis in diseases such as diabetic retinopathy and Kaposi's sarcoma.