Commentary
Xanthine oxidoreductase is an enzyme that catalyses hypoxanthine to xanthine and xanthine to uric acid, respectively. However, the underlying mechanisms of increased plasma xanthine oxidoreductase and its pathological roles in systemic diseases, such as atherosclerosis, are not fully understood. In a mouse model of NAFLD/NASH, plasma xanthine oxidoreductase activity markedly increased. In their NASH mice, the authors observed an increased vascular neointima formation consisting of dedifferentiated vascular smooth muscle cells, which was significantly attenuated by a selective xanthine oxidoreductase inhibitor. In vitro, human liver S9-derived xanthine oxidoreductase (S9 is a supernatant fraction obtained from a liver homogenate by centrifuging at 9000 g) promoted proliferation of smooth muscle cells and induced ROS production by catabolising hypoxanthine released from human endothelial cells. These results suggest that increased plasma xanthine oxidoreductase activity, mainly explained by excess hepatic leakage, is involved in the pathogenesis of vascular injury, especially in NAFLD/NASH conditions.
