The dual role of the urokinase receptor system in pericellular proteolysis and cell adhesion: implications for cardiovascular function

Abstract

Cell-cell and cell-matrix interactions are key events in morphogenetic processes during development and tissue remodelling. In the vascular system, overexpression of adhesion receptors such as integrins, protease (receptors) or dysregulation of adhesive interactions are directly related to the pathophysiology of cardiovascular diseases (atherosclerosis, restenosis, thrombosis) or angiogenesis-driven tumor progression. Protease cascades such as the plasminogen activation system exhibit a dual role in cell invasion by promoting pericellular proteolysis as well as by regulating cell adhesion and migration in a non-proteolytic fashion. In both these mechanisms, the urokinase receptor (uPAR) plays a central role and may become engaged in complexes with β₁–, β₂–, and β₃–integrins. This article will focus on the molecular and funtional interactions between the uPAR system and vascular integrins and discuss implications for cardiovascular function.