Expression of extracellular matrix proteins accompanies lesion growth in a model of intimal reinjury.
Reinjury of rat arterial lesions induces an increase in lesion size that is not associated with an increase in cell number. In this study, matrix volume was examined after reinjury to preexisting lesions, and the kinetics of matrix gene expression and activity of proteolytic enzymes in the lesion were evaluated. Volume densitometry in intima showed a significant increase in matrix volume 28 days after the reinjury, although no change was observed at 14 days. Three common vascular matrix molecules, alpha1(I)procollagen, tropoelastin, and fibronectin, were expressed highly at 7 days after the reinjury. Expression of tropoelastin remained upregulated for the entire 28 days after the reinjury, whereas alpha1(I)procollagen and fibronectin returned to the control level by 28 days. Protease activity was also increased after reinjury. Within days, a marked increase in urokinase plasminogen activator activity was observed in intima, and this activity decreased to control level by 14 days. The activity of tissue plasminogen activator did not change. The 95-kDa gelatinolytic activity was increased 1 to 2 days after the reinjury, but no change in other gelatinolytic activities was observed. These findings demonstrate that the accumulation of extracellular matrix is important in the increase in lesion size after reinjury and that a balance of matrix synthesis and degradation may explain why no change in matrix volume was detected until 28 days after the reinjury.
Koyama
H
H
Department of Pathology, University of Washington, Seattle 98195-7335, USA.
Reidy
M A
MA
D000818:Animals; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010960:Plasminogen Activators / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics; D017539:Tunica Intima / Q000293:injuries* / Q000378:metabolism / Q000648:ultrastructure
D016326:Extracellular Matrix Proteins; D017395:Plasminogen Activator Inhibitor 1; D016212:Transforming Growth Factor beta; D010960:Plasminogen Activators; D018093:Gelatinases