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

• Published in: The Journal of laboratory and clinical medicine 1999-06, Vol.133 (6), p.605-612
• Main Authors: Belcher, J.D, Marker, P.H, Geiger, P, Girotti, A.W, Steinberg, M.H, Hebbel, R.P, Vercellotti, G.M
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anemia, Sickle Cell - metabolism; Anemias. Hemoglobinopathies; Animals; Aorta - drug effects; Aorta - pathology; Biological and medical sciences; Child; Child, Preschool; Diseases of red blood cells; Endothelium, Vascular - drug effects; Endothelium, Vascular - pathology; Hematologic and hematopoietic diseases; Heme - metabolism; Humans; In Vitro Techniques; Iron - metabolism; Lipid Peroxidation; Lipoproteins, LDL - metabolism; Lipoproteins, LDL - pharmacology; Medical sciences; Middle Aged; Oxidation-Reduction; Swine; Time Factors
• ISSN: 0022-2143; 1931-5244; 1532-6543; 1878-1810
• DOI: 10.1016/S0022-2143(99)90191-9

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.