Histopathologic analysis of in-stent neointimal regression in a porcine coronary model

BACKGROUND: Animal and clinical studies have demonstrated late regression of in-stent neointima. This study was performed to identify the temporal changes in the in-stent neointimal constituents responsible for late regression. METHODS: NIR stents were implanted in porcine coronary arteries (size of stent (in mm) to size of artery (in mm) approximately equal to 1.1) and harvested at 2 months and 6 months (n = 6 stents/group). Histopathologic analyses included morphometric analysis, smooth muscle cell density, and extracellular matrix contents. RESULTS: Compared with the findings at 2 months, at 6 months there was a significant reduction in area stenosed (from 21 +/- 3% to 14 +/- 1%, P < 0.05) and neointimal thickness (from 0.2 +/- 0.03 mm to 0.03 +/- 0.02 mm, P < 0.05), despite similar injury scores (0.05 +/- 0.06 at 2 months and 0.36 +/- 0.29 at 6 months). This regression was accompanied mainly by a reduction in proteoglycan (from 24 +/- 19% to 5 +/- 8%, P = 0.05), with no change in smooth muscle cell density (71 +/- 7 compared with 76 +/- 23/high power field) or collagen content (25 +/- 19% compared with 25 +/- 19%). CONCLUSIONS: The study confirmed the regression of in-stent neointima, which was mainly attributable to a reduction in proteoglycan content, resembling the natural healing response.