THE ROLE OF PLASMINOGEN, PLASMINOGEN ACTIVATORS, AND MATRIX METALLOPROTEINASES IN PRIMATE ARTERIAL SMOOTH-MUSCLE CELL-MIGRATION

The migration of arterial smooth muscle cells (SMCs) plays an importan t role in normal vessel development as well as the pathobiology of blo od vessels. Because it is difficult to study cell migration in primate s, we used ex vivo explants. The response of baboon aortic medial expl ants incubated in vitro in a serum-free medium with insulin and transf errin was compared with the response of whole artery injured in vivo b y a balloon catheter to establish the validity of the explant model. B oth the time course of entry of SMCs into the S phase and the changes in matrix metalloproteinase 9 were similar in the artery and the expla nts. SMCs began migrating from explants after a lag of 3 days. By day 11, >90% of the explants exhibited SMC migration from the tissue (perc ent of explants with greater than or equal to 1 migrating cell). Basal migration was inhibited by antibodies to urokinase and tissue-type pl asminogen activator, whereas addition of plasminogen to the explants i ncreased migration. An inhibitor of matrix metalloproteinases, BB-94 ( Batimistat), decreased migration, as did alpha(2)-macroglobulin. These data demonstrate that proteinases of the matrix metalloproteinase and plasminogen/plasminogen activator families play an important role in the migration of primate arterial SMCs through the extracellular matri x.