Depletion of haptoglobin and hemopexin promote hemoglobin-mediated lipoprotein oxidation in sickle cell disease

Intravascular sickling and lysis of red blood cells (RBC), a hallmark feature of sickle cell disease (SCD), releases hemoglobin into the circulation. Increased cell-free Hb has been linked to vasculopathy and in vitro lipid oxidation. Scavenger plasma proteins haptoglobin (Hp) and hemopexin (Hpx) can attenuate cell-free Hb and total plasma heme lipid-oxidative capacity but are depleted in SCD. Here, we isolated lipids from BERK-SS mice, Guinea pigs (GP) infused with heme-albumin and SCD patients undergoing regular exchange transfusion therapy and evaluated the level of lipid oxidation. Malondialdehyde (MDA) formation, an end product of lipid peroxidation, was increased in BERK-SS mice, purified lipid fractions of the heme-albumin infused GP and SCD patients compared to controls. In humans the extent of lipid oxidation was associated with the absence of Hp as well as decreased Hpx in plasma samples. Post-mortem pulmonary tissue obtained from SCD patients demonstrated oxidized LDL deposition in the pulmonar...