Human endothelial cells grow poorly on vitronectin: Role of PAI-1

The cell adhesive protein vitronectin is a common component of interstitial extracellular matrix and circulates in plasma. it competes effectively wit h other plasma proteins to adsorb to certain biomaterial surfaces, and is l ikely to represent an important cell adhesion mediator on the luminal surfa ce of vascular grafts. It is also found associated with certain vascular pa thologies. We have shown previously that human endothelial cells grow poorl y on a vitronectin surface compared with other extracellular matrix molecul es. In this paper we show that endothelial cells seeded on vitronectin and fibronectin produced substantially different profiles of extracellular matr ix molecules. The most outstanding difference was in the amount of matrix-l ocalised plasminogen activator-inhibitor-1 which was high on vitronectin an d negligible on fibronectin. This was correlated with a small but significa nt inhibition of cell adhesion to vitronectin compared with fibronectin, an d very significant interference with dissociation of cell: extracellular ma trix contacts, resulting either from direct inhibition of the proteolytic a ctivity of urokinase, or from interference with urokinase-receptor signalin g and consequent focal adhesion turnover. Such interference would inhibit c ell proliferation by disabling the cells from loosening their matrix contac ts in order to proceed through mitosis. This would seriously compromise end othelial recovery in cases of damage to the vascular wall and placement of stents or grafts, where the presence of surface-adsorbed vitronectin is lik ely to modulate the tissue response.