Abstract
The plasminogen/plasmin system is involved in vascular wall remodeling after injury, through extracellular matrix (ECM) degradation and proteinase activation. Vascular smooth muscle cells (VSMCs) synthesize various components of the plasminogen/plasmin system. We investigated the conversion of plasminogen into plasmin in primary cultured rat VSMCs. VSMCs efficiently converted exogenous plasminogen into plasmin in a time‐ and dose‐dependent manner. We measured plasmin activity by monitoring the hydrolysis of Tosyl‐G‐P‐R‐Mca, a fluorogenic substrate of plasmin. Cell‐mediated plasmin activation was associated with the degradation of ECM, as revealed by fibronectin proteolysis. Plasmin also activated a proteinase able to hydrolyze Mca‐P‐L‐G‐L‐Dpa‐A‐R‐NH~2~, a fluorogenic substrate of matrix metalloproteinases (MMPs). However, this proteinase was not inhibited by an MMP inhibitor. Furthermore, this proteinase displayed similar biochemical and pharmacological properties to fibronectin‐proteinase, a recently identified zinc‐dependent metalloproteinase located in the gelatin‐binding domain of fibronectin. These results show that VSMCs convert exogenous plasminogen into plasmin in their pericellular environment. By hydrolyzing matrix protein plasmin activates a latent metalloproteinase that differs from MMP, fibronectin‐proteinase. This metalloproteinase may participate to vascular wall remodeling, in concert with other proteinases. J. Cell. Biochem. 88: 1188–1201, 2003. © 2003 Wiley‐Liss, Inc.