Reduced paraoxonase1 activity is a risk for atherosclerosis in patients with systemic lupus erythematosus
Reduced paraoxonase1 activity is a risk for atherosclerosis in patients with systemic lupus erythematosus
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DOI：
10.1196/annals.1422.009
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Paragh, Gyoegy
中科院分区：
文献类型：
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作者：
Kiss, Emese;Seres, Ildiko;Paragh, Gyoegy
在系统性红斑狼疮 (SLE) 患者中观察到，过度的脂质过氧化是加速动脉粥样硬化的主要因素。我们本研究的目的是确定 37 名 SLE 患者和 30 名年龄/性别匹配的对照者的对氧磷酶 1 (PON1) 和芳基酯酶活性以及血脂谱。分析了 PON1 活性与 SLEDAI、CRP、抗 oxLDL 和抗磷脂抗体 (aPL) 水平、类固醇剂量和动脉粥样硬化血栓事件之间的关联。患者年龄为 40.8 +/- 13.9 岁，随访时间 6.7 +/- 6.2 年，SLEDAI 2 (0-15)。分别使用对氧磷和乙酸苯酯作为底物，通过分光光度法测量 PON1 和芳基酯酶活性。通过双底物法测定PON1的表型分布。我们通过 ELISA 测量抗氧化低密度脂蛋白 (antioxLDL) 和 aPL 水平，通过自动免疫分析测量 CRP 水平。与对照组 (188.1 +/- 78.9 U/mL) 相比，SLE 中的 PON1 活性 (121.9 +/- 65.9 U/mL) 显着降低 (P < 0.001)，但芳基酯酶活性没有差异。 PON1 活性与年龄呈负相关。 PON1 活性与其他测量参数不相关。 PON1 活性降低与临床动脉粥样硬化血栓并发症相关（P < 0.01）。 SLE 中不存在高活性 BB 表型。两组的脂质参数（TC、LDL-C、HDLC、ApoAI 和 ApoB）均在正常范围内。结果表明，尽管狼疮患者病程较长且炎症活性较低，但 PON1 活性降低，并且被证明存在动脉粥样硬化并发症的风险。由于芳基酯酶活性正常，需要进一步检查以发现其他机制，例如抗 PON1 抗体、遗传多态性以及 HDL 亚组分分布差异或 HDL 重塑中的酶异常。
Excessive lipid peroxidation is a major factor of accelerated atherosclerosis, observed in patients with systemic lupus erythematosus (SLE). We aimed at the present study to determine the paraoxonase1 (PON1) and arylesterase activities, and lipid-profile in 37 SLE patients and 30 age-/sex-matched controls. Association was analyzed between PON1 activity and SLEDAI, CRP, anti-oxLDL, and antiphospholipid antibody (aPL) levels, steroid dose, and atherothrombotic events. The age of patients was 40.8 +/- 13.9 year, follow-up time 6.7 +/- 6.2 year, SLEDAI 2 (0-15). PON1 and arylesterase activities were measured spectrophotometrically using paraoxon and phenyl acetate as substrates, respectively. Phenotypic distribution of PON1 was determined by dual substrate method. We measured antioxLDL and aPL levels by ELISA, the CRP by automated immunoassay. PON1 activity (121.9 +/- 65.9 U/mL) was reduced significantly (P < 0.001) in SLE as compared to control (188.1 +/- 78.9 U/mL), but arylesterase activity was not different. A negative correlation was found between PON1 activity and age. PON1 activity did not correlate with other measured parameters. Reduced PON1 activity associated with clinical atherothrombotic complications (P < 0.01). High activity BB phenotype was not present in SLE. Lipid parameters (TC, LDL-C, HDLC, ApoAI, and ApoB) were within normal range in both groups. Results indicated reduced PON1 activity in lupus patients despite long disease duration and low inflammatory activity, and it was evidenced as a risk for atherosclerotic complications. As the arylesterase activity was normal, further examinations are required to find other mechanisms, such as anti-PON1 antibodies, genetic polymorphisms, and difference in distribution of HDL-subfractions or enzyme abnormalities in HDL remodeling.