The plasminogen activation system plays a role in the migration of human smooth muscle cells in vitro (abstract)

The plasminogen activation system is known to be involved in several cell migration processes. A role for plasminogen activators in smooth muscle cell migration after vascular injury has been suggested from several animal studies. However, not much is known about their involvement in human vascular remodelling. In this study, the role of the plasminogen activation system in human smooth muscle cells was investigated in more detail using an in vitro wound assay. Confluent cultures were wounded by stripping the cells away from their extracellular matrix with the use of Millipore strips. After wounding, cells start to migrate from the wounded edge into the denuded area. Migration was followed during 24 hours and quantified by counting the number of cells that migrated into the denuded area. Migration was inhibited to 61.9 + 7.1 % of control by the addition of the plasmin inhibitor aprotinin (100 KIU/mL) to the culture medium. Blocking the activity of u-PA or t-PA using specific polyclonal antibodies reduced migration to 57.8 ±6.1% with anti-uPA and had no significant effect on migration with anti-tPA. Interference in the uPA/uPAR interaction by addition of soluble uPAR had a similar effect as for anti-uPA. A possible involvement of LRP or the VLDL receptor was shown by adding the receptor antagonist RAP to the culture medium, which inhibited migration to 61.0 ± 7.9 % of control. These results suggest an involvement of the plasminogen activation system and particularly surface bound u-PA in human smooth muscle cell migration