EXPRESSION OF EXTRACELLULAR-MATRIX PROTEINS ACCOMPANIES LESION GROWTHIN A MODEL OF INTIMAL REINJURY

Reinjury of rat arterial lesions induces an increase in lesion size th at is not associated with an increase in cell number. In this study, m atrix volume was examined after reinjury to preexisting lesions, and t he kinetics of matrix gene expression and activity of proteolytic enzy mes in the lesion were evaluated. Volume densitometry in intima showed a significant increase in matrix volume 28 days after the reinjury, a lthough no change was observed at 14 days. Three common vascular matri x molecules, alpha(1)(I)procollagen, tropoelastin, and fibronectin, we re expressed highly at 7 days after the reinjury. Expression of tropoe lastin remained upregulated for the entire 28 days after the reinjury, whereas alpha(1)(I)procollagen and fibronectin returned to the contro l level by 28 days. Protease activity was also increased after reinjur y. Within days, a marked increase in urokinase plasminogen activator a ctivity was observed in intima, and this activity decreased to control level by 14 days. The activity of tissue plasminogen activator did no t change. The 95-kDa gelatinolytic activity was increased 1 to 2 days after the reinjury, but no change in other gelatinolytic activities wa s observed. These findings demonstrate that the accumulation of extrac ellular matrix is important in the increase in lesion size after reinj ury and that a balance of matrix synthesis and degradation may explain why no change in matrix volume was detected until 28 days after the r einjury.