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Low-density lipoprotein composition and oxidability in atherosclerotic cardiovascular disease
L E Schreier1, S Sanguinetti, H Mosso
1Department of Clinical Biochemistry, Faculty of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Objectives:
To characterize low-density lipoprotein (LDL) chemical composition and oxidability in normolipidemic and dyslipidemic patients with atherosclerotic cardiovascular disease, as compared with matched control subjects. To evaluate LDL susceptibility to oxidation, we determined the cutoff points of thiobarbituric reactive substances (TBARS) in LDL after oxidative stress, as well as its resistance to oxidation.
Design And Methods:
LDL (density 1.019-1.063 g/mL) of 24 men with atherosclerotic cardiovascular disease (12 normolipidemic and 12 dyslipidemic patients) and 18 age-matched healthy control men. LDL chemical composition was determined and apo B/cholesterol ratio was calculated. TBARS in native LDL and after 60 and 120 min of LDL oxidation with copper were measured. The conjugated diene production kinetics during LDL incubation with copper were also studied, lag time being an oxidation resistance marker. Cutoff points for the positivity criterion of apoB/cholesterol ratio in LDL and TBARS in native and oxidized LDL were evaluated using the receiver operator characteristic (ROC) graphic method.
Results:
LDL were triglyceride-enriched, the apoB/cholesterol ratio being higher in patients than in controls, without differences between normolipidemic and dyslipidemic subgroups. We have established the following cutoff values to differentiate between patients and controls: 0.43 mg/mg for the apo B/cholesterol ratio in LDL; 3.0 nmol malondialdehyde/mg protein for TBARS in native LDL; 22 and 80 nmol malondialdehyde/mg protein after 60- and 120-min postoxidative stress, respectively. We did not find differences in the conjugated diene production kinetics between patients and controls.
Conclusions:
The enrichment in triglycerides and the high apoB/ cholesterol ratio suggest the presence of an abnormal LDL particle in normolipidemic and dyslipidemic patients. This LDL particle was more susceptible to oxidation. In the ROC analysis, the TBARS plot at 120 min exhibited greater accuracy and better performance than the other LDL oxidability markers.