Recent studies have shown that migration of arterial smooth muscle cells (SMC) from the media into the intima is an important step in the development of arterial lesions. Little is known about the factors which stimulate SMC migration, nor what events are important for the migration of SMC. In this proposal we will examine the role of selected proteases which are known to be important for the movement of cells. In particular, we will measure the expression and the proteolytic activity of interstitial collagenase, gelatinases, stromelysin and plasminogen activators in rat carotid arteries subjected to balloon catheter injury and correlate their presence with SMC migration. Further, the activity of these molecules will be analyzed in situations where migration is inhibited. The role of growth factor in control of SMC migration will be tested by measuring modulation of migration after stimulation with these recombinant factors and by inhibiting their action with specific antibodies. Inhibitors of plasminogen activators and metalloproteinases will be added to in vivo models of cell migration to determine the relative importance of these pathways. Another group of studies is proposed to identify factor(s) expressed by SMC which are both important and unique for SMC migration. This will be carried out by screening a rat DNA library made from SMC which have been stimulated to migrate, with minimal replication, and from rat SMC which are quiescent. These studies will utilize differential display and subtractive hybridization. Finally, a clone(s) which satisfies our criteria of """"""""migration specific"""""""" will be sequenced.
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