Differential expression of proteoglycans biglycan and decorin during neointima formation after stent implantation in normal and atherosclerotic rabbit aortas

Abstract

Proteoglycans decorin and biglycan, which bind to TGF-β, 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-β and IL-1β, 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-β and biglycan expression was in correspondence with the chronology and localization of embryonic SMCs. In the atherosclerotic group, TGF-β 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.