Proteoglycans decorin and
biglycan, which bind to
TGF-beta, are thought to participate in regulation of extracellular matrix accumulation in arterial intimal
hyperplasia. To investigate the correlation of these
proteoglycans with the cellular localization and phenotypic modulation of smooth muscle cells (SMCs), we analyzed the spatial and chronological distribution of these
proteoglycans and two
cytokines,
TGF-beta and IL-1beta, in the process of
neointima formation after
stent implantation in the aortas of rabbits fed a high-
cholesterol diet (atherosclerotic group) or a regular diet (control group). We implanted metallic
stents in the rabbit aortas and harvested the aortas 4-56 days later for immunohistochemical and
mRNA in situ hybridization analyses. In the control group,
TGF-beta and
biglycan expression was in correspondence with the chronology and localization of embryonic SMCs. In the atherosclerotic group,
TGF-beta and
biglycan expression was sustained throughout the experimental period, which was in accord with the prolonged expression of embryonic SMCs.
Decorin, which did not occur in
neointima in the control group, appeared in the atherosclerotic aortas in the confined area of vascular SMCs surrounding the macrophages around the
stent wire. These results indicate that
biglycan and
decorin kinetics during
neointima formation after arterial injury are distinct, despite their similar construction;
biglycan synthesis correlates with embryonic SMCs.