Stanisavljevic Natasa, Stojanovich L, Marisavljevic D, Djokovic A, Dopsaj V, Kotur-Stevuljevic J, Martinovic J, Memon L, Radovanovic S, Todic B, Lisulov D
University Clinical Center "Bezanijska kosa", Bezanijska kosa bb, Belgrade, 11070, Serbia.
Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
Clin Rheumatol. 2016 Oct;35(10):2485-93. doi: 10.1007/s10067-016-3369-8. Epub 2016 Aug 25.
The aim of this study was to evaluate oxidative stress markers and it relations to endothelial damage as risk factor for thrombosis in patients with primary (PAPS) and secondary (SAPS) antiphospholipid syndrome (APS) in correlation to traditional risk factors. Flow-mediated (FMD) and nitroglycerine (NMD)-induced dilation of the brachial artery were studied in 140 APS patients (90 PAPS, 50 SAPS) and 40 controls matched by age, sex, and conventional risk factors for atherosclerosis. Markers of oxidative stress, lipid hydroperoxydes (LOOH), advanced oxidation protein products (AOPP), total sulfhydryl groups (tSHG), and paraoxonase 1 activity (PON1) were determined by spectrophotometric method. Oxidative stress dominates in APS patients. LOOH and AOPP correlate to lipid fractions (p < 0.05), unlike PON1, tSHG that correlated to antiphospholipid antibody positivity (p < 0.05). FMD was lower in APS patients comparing to controls (p < 0.001). Cholesterol is independent variable for FMD impairment in control group (p = 0.011); LOOH in PAPS (p = 0.004); LOOH, aCL, and triglycerides in SAPS patients (p = 0.009, p = 0.049, and p = 0.012, respectively). Combined predictive of aCL and LOOH is better for FMD impairment than LOOH alone in both PAPS and SAPS patients (AUC 0.727, p = 0.001, 95 % CI 0.616-0.837 and AUC 0.824, p˂0.001, 95 % CI 0.690-0.957, respectively). Lipid peroxidation is independent predictor for endothelial dysfunction in APS patients. We demonstrated synergistic effect of aCL and LOOH as risk for endothelial impairment in both PAPS and SAPS patients.
本研究旨在评估氧化应激标志物及其与内皮损伤的关系，内皮损伤作为原发性抗磷脂综合征（PAPS）和继发性抗磷脂综合征（SAPS）患者血栓形成的危险因素，并与传统危险因素进行相关性分析。对140例抗磷脂综合征患者（90例PAPS，50例SAPS）和40例年龄、性别及动脉粥样硬化传统危险因素相匹配的对照者进行了肱动脉血流介导的血管舒张功能（FMD）和硝酸甘油诱导的血管舒张功能（NMD）研究。采用分光光度法测定氧化应激标志物，包括脂质氢过氧化物（LOOH）、晚期氧化蛋白产物（AOPP）、总巯基（tSHG）和对氧磷酶1活性（PON1）。氧化应激在抗磷脂综合征患者中占主导地位。LOOH和AOPP与血脂成分相关（p<0.05），而PON1、tSHG与抗磷脂抗体阳性相关（p<0.05）。与对照组相比，抗磷脂综合征患者的FMD较低（p<0.001）。在对照组中，胆固醇是FMD受损的独立变量（p=0.011）；在PAPS患者中为LOOH（p=0.004）；在SAPS患者中为LOOH、抗心磷脂抗体（aCL）和甘油三酯（分别为p=0.009、p=0.049和p=0.012）。在PAPS和SAPS患者中，aCL和LOOH联合预测FMD受损的效果均优于单独的LOOH（AUC分别为0.727，p=0.001，95%CI为0.616-0.837和AUC为0.824，p<0.001，95%CI为0.690-0.957）。脂质过氧化是抗磷脂综合征患者内皮功能障碍的独立预测因素。我们证明了在PAPS和SAPS患者中，aCL和LOOH作为内皮损伤风险因素具有协同作用。
