Background Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing a cardiovascular disease which are not solely explained by the traditional cardiovascular (CV) risk factors. This higher CV risk might be associated with chemical and functional alteration of lipoproteins in SLE patients.
Objectives This study aimed to investigate the lipoprotein modification from SLE patients and its effects on oxidative stress in vivo and in vitro.
Methods A total of 35 SLE patients and 15 age and sex matched heathy controls (HC) were compared in regard to lipid profile including low density lipoprotein (LDL). Oxidation and susceptibility to oxidation as well as structure of LDL were measured by quantifying malondialdehyde (MDA), de novo formation of conjugated dienes in the presence of 5 uM CuSO4 and gel electrophoresis, respectively. The uptake of LDL by THP-1 cells was examined. In vivo radial oxygen species (ROS) formation and toxicity of LDL were examined in zebra fish embryos.
Results LDL levels did not differ between SLE and HC (134.7±54.5 mg/dL vs. 118.3±29.9 mg/dL, P=0.277). LDL from SLE showed an increased fragmentation pattern during mobility through electrophoresis gel. As compared to HC-LDL, SLE-LDL were more oxidized (MDA level: 56.1±10 vs. 25.4±2.3 nM/mg, p<0.001) and were also more susceptible to cupric-ion-mediated oxidation in vitro (3.5±0.5% vs. 1.9±1.9%, p<0.001). In addition, more SLE-LDL were engulfed by THP-1 cells than HC-LDL (2501±401.2 AU vs. 524.1±59.8 AU, p<0.001). Finally, the zebra fish embryos that were injected with SLE-LDL generated higher levels of ROS (1592±58.7 vs. 459.6±66.4, p<0.001) and survived less (survival 49.1±2.8% vs. 87.8±1.2%, p<0.001) as compared to those treated with HC-LDL.
Conclusions LDL from SLE patients is altered with increased oxidation, structural instability and an augmented oxidative potential. Treatment with anti-oxidants might normalize the altered LDL property and so decrease the CV risk in SLE patients.
Disclosure of Interest None declared
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