SMOOTH-MUSCLE CELL-PROLIFERATION, ELASTIN FORMATION, AND TROPOELASTINTRANSCRIPTS DURING THE DEVELOPMENT OF INTIMAL THICKENING IN RABBIT CAROTID ARTERIES AFTER ENDOTHELIAL DENUDATION

Extracellular matrix formation and smooth muscle cell proliferation ar e two major factors contributing to the development of intimal thicken ing after arterial injury. We investigated the elastin formation, trop oelastin transcripts, and proliferation of smooth muscle cells during the development of intimal thickening in rabbit carotid arteries after balloon endothelial denudation. Tropoelastin transcripts, identified by in situ hybridization using a digoxigenin-labeled probe, and elasti n staining in the thickened intima were minimal 1 week after endotheli al denudation when smooth muscle cell proliferation appeared throughou t the thickened intima. A strong signal for tropoelastin transcripts w as seen in the basal layer of the thickened intima 2 weeks after endot helial denudation, and then in the surface layer of the thickened inti ma 4 weeks after endothelial denudation. Immunohistochemistry for prol iferating cell nuclear antigen and Ki-67, both markers for proliferati ng cell nuclei, showed that tropoelastin transcripts and elastin forma tion increased when smooth muscle cells enter quiescence after the end of the proliferative phase in the intima. Our findings strongly sugge st that elastin synthesis and smooth muscle cell proliferation are tig htly regulated during the repair of arterial wall injury.