The Role of Endothelial Superoxide Dismutase 2 in Modulating Sickle Pathology

Sickle cell disease (SCD) patients suffer from hemolysis in microcirculation. On the one hand, hemoglobin and heme released from sickled red blood cells catalyze reactive oxygen species (ROS) generation by Fenton chemistry. On the other hand, sickled red blood cells occlude capillaries, creating a hypoxic condition that exacerbates ROS production. As an essential antioxidant mechanism, superoxide dismutase 2 (SOD2) detoxifies superoxide by converting it to hydrogen peroxide (H 2O 2) in the mitochondria. In SCD patients, despite the elevated ROS production, we found that SOD2 expression is suppressed in the pulmonary endothelium (Figure 1A,B). Therefore, we hypothesize the depletion of endothelial SOD2 compromises endothelial function and exacerbates the progression of SCD.