Transient Morphological and Biochemical Alterations of Arterial Proteoglycan during Early Wound Healing

Abstract

Proteoglycan alterations in the carotid arteries of normolipemic rabbits during the first 14 days after injury were evaluated by morphometric analysis of ruthenium red-stained sections using transmission electron microscopy and by incorporation of 35S-sulfate. Two types of de-endothelializing injury were compared, air-drying and balloon catheter. Three days after either injury, a transient increase in concentration of 35S-labeled glycosaminoglycans, changes in distribution of 35S-sulfate among glycosaminoglycans, and a two- to threefold increase in 35S-sulfate content (measured as 35S/μg glycosaminoglycan) were observed. Morphometric analysis revealed an alteration in medial proteoglycan distribution and morphology at 3 days after injury, which was more evident after air-drying than balloon injury. In response to either injury, metabolically activated smooth muscle cells were associated with very large proteoglycan granules (diameter: >60 nm) which possibly contained glycosaminoglycans with longer chains and/or altered charge densities. By 14 days after either injury, the distribution of medial proteoglycan returned to normal and a neointima formed. The neointima was thicker following balloon injury, but irrespective of the nature of the injury proteoglycan concentration was higher in the re-endothelialized than in non-reendothelialized areas. The alterations in extracellular proteoglycan of the intima-medial layers induced by these two forms of injury may influence the pattern of wound healing but are not associated with lipid deposition within the time frame examined.