Low-density lipoprotein susceptibility to oxidation and cytotoxicity to endothelium in sickle cell anemia

Patients with sickle-cell anemia exhibit pro-oxidative metabolic perturbati ons. We hypothesize that because of chronic oxidative stress, plasma low-de nsity lipoprotein (LDL) from patients with sickle-cell anemia is more susce ptible to oxidation. To test this hypothesis, LDL susceptibility to copper- mediated oxidation was measured in 24 patients with sickle-cell anemia and 48 control subjects. Sickle-cell LDL was more susceptible to oxidation than control LDL, measured by a 22% shorter mean lag time between LDL exposure to CuSO4 and conjugated diene formation (97 vs 124 minutes; P=.023). LDL vi tamin E, iron, heme, and cholesterol ester hydroperoxide (CEOOH) levels wer e also measured. LDL vitamin E levels were significantly lower in patients with sickle-cell anemia compared with control subjects (1.8 vs 2.9 mol/mol LDL; P =.025), but there was no correlation with lag time. Pro-oxidant heme and iron levels were the same in sickle-cell and control LDL. LDL CEOOHs w ere not significantly different in sickle and control LDL (3.1 vs 1.2 mmol/ mol of LDL unesterified cholesterol, P =.15), but LDL CEOOH levels were inv ersely correlated with lag times in patients with sickle-cell anemia (r(2) = 0.38; P=.018). The cytotoxicity of partially oxidized LDL to porcine aort ic endothelial cells was inversely correlated with lag times (r(2) = 0.48; P =.001). These preliminary data suggest that increased LDL susceptibility to oxidation could be a marker of oxidant stress and vasculopathy in patien ts with sickle-cell anemia.