Impact of elevated red blood cell membrane cholesterol in sickle cell anemia patients: Effects of BRN-002, a 2-hydroxypropyl-β-cyclodextrin derivate, on red blood cell lipids, deformability, sickling and hemolysis.

Sickle cell anemia (SCA) patients are characterized by poorly deformable and fragile red blood cells (RBCs). Few studies reported an increased cholesterol content in SCA RBC membrane. However, the consequences of this elevated cholesterol level in the above-mentioned RBC alterations are currently unknown. The aim of this study was to assess, in vitro, the effects of BRN-002 (2-Hydroxypropyl-β-cyclodextrin derivate (HPBCD)), a cholesterol-depleting molecule, on RBC membrane cholesterol, hemolysis and RBC sickling and deformability in SCA patients. Forty patients with SCA and 10 healthy individuals (AA) were included in the different experiments of the study. SCA RBCs were incubated with BRN-002 and the following parameters were assessed: i) RBC and supernatant cholesterol content; ii) RBC deformability by oxygen-gradient ektacytometry; iii) hemolysis by measuring free hemoglobin concentration. Results confirmed that SCA patients have increased RBC membrane cholesterol compared to AA. BRN-002 effectively removed cholesterol in SCA RBC membrane and reduced free hemoglobin release during incubation. BRN-002 also increased RBC deformability in hypoxia and decreased the pO2 at which sickling occurs. These findings suggest that excess of RBC membrane cholesterol may participate in the typical RBC alterations found in SCA patients. Therefore, interventions focusing on RBC-cholesterol removal may be beneficial for SCA patients.