title: Low-density lipoprotein susceptibility to oxidation and cytotoxicity to endothelium in sickle cell anemia.
abstract: Patients with sickle-cell anemia exhibit pro-oxidative metabolic perturbations. We hypothesize that because of chronic oxidative stress, plasma low-density lipoprotein (LDL) from patients with sickle-cell anemia is more susceptible 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 vitamin E, iron, heme, and cholesterol ester hydroperoxide (CEOOH) levels were 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 were 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 inversely correlated with lag times in patients with sickle-cell anemia (r2 = 0.38; P = .018). The cytotoxicity of partially oxidized LDL to porcine aortic endothelial cells was inversely correlated with lag times (r2 = 0.48; P = .001). These preliminary data suggest that increased LDL susceptibility to oxidation could be a marker of oxidant stress and vasculopathy in patients with sickle-cell anemia.
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Belcher
authors.forename: P H
authors.initials: PH
authors.lastname: Marker
authors.forename: P
authors.initials: P
authors.lastname: Geiger
authors.forename: A W
authors.initials: AW
authors.lastname: Girotti
authors.forename: M H
authors.initials: MH
authors.lastname: Steinberg
authors.forename: R P
authors.initials: RP
authors.lastname: Hebbel
authors.forename: G M
authors.initials: GM
authors.lastname: Vercellotti
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D006418:Heme / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008875:Middle Aged; D010084:Oxidation-Reduction; D013552:Swine; D013997:Time Factors
chemical_list: D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D006418:Heme; D007501:Iron