DIFFERENTIAL EXPRESSION OF ALPHA(1) TYPE-VIII COLLAGEN IN INJURED PLATELET-DERIVED GROWTH FACTOR-BB-STIMULATED RAT CAROTID ARTERIES

Migration of smooth muscle cells from media to intima is critical for the development of neointimal thickening after balloon catheter injury of the rat carotid artery. The present experiments were designed to i dentify molecules expressed by smooth muscle cells migrating in vivo i n the injured artery. Cell migration was maximized by infusing recombi nant platelet-derived growth factor-BB (PDGF-BB) after a minimal filam ent denudation of the rat carotid artery, whereas cell proliferation w as minimized by injecting an antibody against basic fibroblast growth factor (bFGF). This treatment caused an eightfold increase in smooth m uscle cell migration into the intima but only a twofold increase in in timal smooth muscle cell replication rates. Differential display scree ning was used to isolate cDNAs that were overexpressed in the injured PDGF-BB-treated versus unmanipulated rat carotids. One of the clones i solated hybridized to a 4.2-kb mRNA species and shared 90% sequence ho mology to mouse cui type VIII collagen. Northern and Western blots con firmed overexpression of type VIII collagen in the injured PDGF-BB-tre ated vessels. In a separate series of experiments, we per formed filam ent denudation injury and administered antibodies to inhibit the actio ns of endogenous bFGF and PDGF-BB, thereby decreasing smooth muscle ce ll migration, and found that type VIII collagen mRNA expression varied with migration. Using a different arterial injury model (balloon cath eter injury), we showed that expression of type VIII collagen was maxi mal 2 to 4 days after injury, in coincidence with cell migration from the media to the intima. This molecule constitutes an important compon ent of smooth muscle cell response to vessel injury and may play an im portant functional role in mediating migration.