Differences in heme and hemopexin content in lipoproteins from patients with sickle cell disease.

ABSTRACT

BACKGROUND: High blood cholesterol is associated with atherogenesis and endothelial dysfunction. The latter is present in hemolytic diseases, such as sickle cell anemia, whose carriers have hypocholesterolemia and low incidence of coronary artery disease. OBJECTIVE: We aimed to characterize cholesterol fractions in patients with sickle cell disease and explore the relationship among lipoproteins, varying degrees of hemolysis, and its biomarkers. METHODS: We recruited 37 healthy individuals, 39 with hemoglobin SC disease, and 40 with sickle cell anemia and quantified cholesterol fractions, heme resulting from hemoglobin breakdown, and its main scavenger protein hemopexin. RESULTS: Hypocholesterolemia was most significant in patients with sickle cell anemia, and cholesterol levels correlated positively with hemopexin. Nevertheless, patients still had higher relative low-density lipoprotein (LDL) oxidation than healthy subjects. Analysis of lipoproteins isolated by density ultracentrifugation showed that the LDL fraction contained higher concentrations of heme than the high-density lipoprotein (HDL) fraction, whereas HDL contained more hemopexin than LDL, albeit greatly reduced in patients. CONCLUSION: Our findings show that the abnormally low lipoprotein levels in sickle cell anemia correlate with hemolysis markers, particularly with hemopexin concentrations, along with significant reduction of this heme scavenger in HDL fractions. This may suggest an important role for HDL in the defense against heme-induced endothelial dysfunction in hemolytic diseases.