Faculty Collaboration Database

Low-density lipoprotein susceptibility to oxidation and cytotoxicity to endothelium in sickle cell anemia. J Lab Clin Med 1999 Jun;133(6):605-12

Date

06/09/1999

Pubmed ID

10360636

DOI

10.1016/s0022-2143(99)90191-9

Scopus ID

2-s2.0-0033153333 (requires institutional sign-in at Scopus site)   37 Citations

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.

Author List

Belcher JD, Marker PH, Geiger P, Girotti AW, Steinberg MH, Hebbel RP, Vercellotti GM

Author

Albert W. Girotti PhD Adjunct Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Anemia, Sickle Cell
Animals
Aorta
Child
Child, Preschool
Endothelium, Vascular
Heme
Humans
In Vitro Techniques
Iron
Lipid Peroxidation
Lipoproteins, LDL
Middle Aged
Oxidation-Reduction
Swine
Time Factors