Xanthine oxidoreductase is a critical mediator of cigarette smoke-induced endothelial cell DNA damage and apoptosis

► Pulmonary endothelial cell apoptosis is an early determinant of emphysema. ► Human pulmonary endothelial cells and C57/bl6 mice were exposed to cigarette smoke. ► Cigarette smoke is sufficient to upregulate XOR activity and expression. ► Cigarette smoke-induced endothelial cell apoptosis is dependent on p53 upregulation. ► XOR activity/expression via DNA damage and ATM activity increase p53 expression.