Oxidative Stress and Lipid Retention in Vascular Grafts

Abstract

Background —Because saphenous vein grafts (SVGs) exhibit greater cellular heterogeneity and worse clinical outcomes than arterial grafts (AGs), we examined oxidative stress and lipid retention in different vascular conduits. Methods and Results —In a porcine model of graft interposition into carotid artery, superoxide anion (·O 2 − ) was measured at 2 weeks after surgery. SVGs demonstrated increased ·O 2 − production compared with AGs (SOD-inhibitable nitro blue tetrazolium reduction, P <0.01). The NAD(P)H oxidase inhibitor diphenyleneiodonium ( P <0.01) abolished SVG-derived ·O 2 − , whereas the inhibitors of other pro-oxidant enzymes were ineffective. The change in oxidative stress was also reflected by lower activity of the endogenous antioxidant superoxide dismutase in SVGs than in AGs ( P <0.001). SVG remodeling was associated with increased synthesis of sulfated glycosaminoglycans and augmented expression of a core protein, versican. These changes were accompanied by SVGs retaining significantly more 125 I-labeled LDL than AGs ex vivo ( P <0.001). In hyperlipemic animals, lipid accumulation and oxidized epitopes were preferentially noted in the intima of SVGs at 1 month after surgery. Conclusions —This study demonstrated significant differences in the biology of SVGs and AGs. SVGs exhibited higher oxidative stress, LDL accumulation, and the presence of oxidized epitopes. These findings suggest that proatherogenic changes in SVGs may commence early after surgical revascularization.