IMPACT OF HIGH DOSE ROSUVASTATIN ON VASCULAR HEALING AFTER BIORESORBABLE VASCULAR SCAFFOLD IMPLANTATION IN A RABBIT AORTOILIAC MODEL

초록

Background and Aims: Delayed vascular healing and inflammation remain major limitations of bioresorbable vascular scaffolds (BVS). Statins have pleiotropic anti-inflammatory and vascular healing effects. This study evaluated the impact of high dose rosuvastatin on neointimal formation and vascular healing following BVS implantation. Methods: Thirty rabbits were assigned to high dose rosuvastatin (10mg/kg) or control groups after Absorb BVS implantation in the aortoiliac arteries. Angiography and optical coherence tomography (OCT) were performed at 1, 6, and 12 months. Histology, immunohistochemistry (IHC), and quantitative real-time polymerase chain reaction (RT-PCR) analyses were used to assess neointimal growth, inflammation and macrophage phenotype. Results: High dose rosuvastatin significantly reduced neointimal thickness (6 months: 0.23 ± 0.05 mm vs. 0.26 ± 0.05 mm, P = 0.03; 12 months: 0.20 ± 0.04 mm vs. 0.24 ± 0.05 mm, P = 0.01) and neointimal area (6 months: 1.80 ± 0.35 mm2 vs. 2.05 ± 0.40 mm2 , P = 0.02; 12 months: 1.70 ± 0.35 mm2 vs. 1.95 ± 0.40 mm2 , P = 0.01) compared with the controls. Expression of IL-1β, IL-6, TNFα, HMGB1, and RAGE was significantly lower in the high dose rosuvastatin group at 1, 6, and 12 months, as demonstrated by both IHC staining and RT-PCR analysis. (all P < 0.05) Macrophage infiltration identified by CD68 and RAM11 staining was also markedly reduced in the rosuvastatin group. (all P < 0.05) Expression of the M1 marker iNOS was significantly decreased, whereas the M2 marker Arg1 expression was increased across all time points in both analyses (all P < 0.05). Conclusions: High dose rosuvastatin enhanced vascular healing after BVS implantation by suppressing inflammation, limiting neointimal hyperplasia, and promoting an anti-inflammatory macrophage phenotype.