Abstract P351: Statins Prevent Expansive Remodeling in Arterialized Vein Grafts

Vein grafts (VG) account for more than 70% of conduits used in aortocoronary bypass surgery, but have high failure rates by 10 years. We have previously shown in an experimental model that VG undergo marked expansion by 4 weeks, which was followed by increased total LDL retention at 12 weeks. The objective of this study was to determine whether statin therapy would prevent these expansive remodelling changes. Methods and Results Reversed jugular vein-to-common carotid artery interposition graft were constructed in 24 cholesterol-fed (0.5%) rabbits. Rabbits were randomized to either control or atorvastatin (5 mg/kg/day) groups, starting two weeks prior to vein graft implantation and continuing until sacrifice at 1 or 12 weeks post-surgery. Ultrasound measurements of arterial luminal cross-sectional area (LCSA) were done at day 3 and at 4, 8 and 12 weeks post-surgery. Histomorphometric measurements were performed following sacrifice at 12 weeks. Atorvastatin treatment significantly decreased total plasma cholesterol levels at 12 weeks (6.70±4.19mmol/L vs placebo 38.65±10.55mmol/L, p<0.001). Atorvastatin significantly reduced expansive remodelling at all time points, including at 12 weeks (44.6±6.62mm 2 vs placebo 77.6±10.68mm 2 , p<0.001). Intimal CSA by histomorphometry was significantly reduced by atorvastatin at 12 weeks (5.59±2.19mm 2 vs placebo 9.57±2.43mm 2 , p<0.05). At 1 week, macrophage infiltration was significantly reduced (Ram11 positive intimal staining 0.018±0.019 vs 0.189±0.049, p<0.05). Atorvastatin treated samples at 1 week showed reduction in both MMP 2 activity (gelatin zymography) and metalloelastase activity (casein zymography). Conclusion: Atorvastatin prevents expansive remodelling in arterialized VG, likely through inhibition of macrophage infiltration and reduction of tissue proteolytic activity. This may be an important mechanism preventing VG atherosclerosis and late VG failure.