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对氧磷酶-1芳基酯酶活性是有或无心血管并发症的超重患者髓过氧化物酶水平的独立预测指标。

Paraoxonase-1 arylesterase activity is an independent predictor of myeloperoxidase levels in overweight patients with or without cardiovascular complications.

作者信息

Zsíros Noémi, Koncsos Péter, Lőrincz Hajnalka, Seres Ildikó, Katkó Mónika, Szentpéteri Anita, Varga Viktória E, Fülöp Péter, Paragh György, Harangi Mariann

机构信息

Institute of Medicine, University of Debrecen Faculty of Medicine, Hungary.

Institute of Medicine, University of Debrecen Faculty of Medicine, Hungary.

出版信息

Clin Biochem. 2016 Aug;49(12):862-7. doi: 10.1016/j.clinbiochem.2016.03.011. Epub 2016 Apr 26.

Abstract

OBJECTIVES

Myeloperoxidase (MPO), matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) were shown to contribute to atherogenesis, while human paraoxonase-1 (PON1) protects against oxidative stress. Although several studies investigated these biomarkers, their associations have not been completely clarified yet. We aimed to investigate these parameters in overweight hyperlipidemic, lipid-lowering therapy-naive patients (n=167) with and without vascular complications.

DESIGN AND METHODS

MPO, MMP-9 and TIMP-1 levels were measured by ELISA. PON1 activities were detected spectrophotometrically. PON1 phenotype was calculated by using a dual substrate method.

RESULTS

Patients with vascular complications (VC) had significantly higher MPO and TIMP-1 levels compared to those without (patients with no vascular complications; NVC) (728 (367.25-1177.90) mg/ml vs. 315.9 (176.05-687.40) mg/ml; p<0.001; and 172.7 (157.7-197.7) ng/ml vs. 152.6 (129.3-172.3) ng/ml; p<0.0001; respectively). MPO levels showed a significant negative correlation with PON1 arylesterase activity (whole patient group (W): r=0.42, p<0.0001; VC: r=0.44, p=0.01; NVC: r=0.39, p<0.0001) and positive correlations with MMP-9 (W: r=0.37, p<0.0001; VC: r=0.29, p=0.07; NVC: r=0.42, p<0.0001) and TIMP-1 (W: r=0.42, p<0.0001; VC: r=0.33, p<0.05; NVC: r=0.41, p<0.0001), respectively. PON1 arylesterase activity was found to be an independent predictor of MPO levels in the whole patient group (β=-0.350, p<0.0001) or when studied separately in the subgroups with or without cardiovascular complications (VC: β=-0.57, p<0.05; NVC: β=-0.33, p<0.0001).

CONCLUSIONS

Our results suggest that parallel investigation of MPO, MMP-9 and TIMP-1 levels and PON1 arylesterase activity may be a more accurate indicator of atherosclerosis, which may allow earlier treatment and therefore, improvement of treatment efficacy.

摘要

目的

髓过氧化物酶(MPO)、基质金属蛋白酶-9(MMP-9)和基质金属蛋白酶组织抑制剂-1(TIMP-1)已被证明与动脉粥样硬化的发生有关,而人对氧磷酶-1(PON1)可抵御氧化应激。尽管有多项研究对这些生物标志物进行了调查,但它们之间的关联尚未完全阐明。我们旨在对167例未接受过降脂治疗、超重的高脂血症患者进行研究,观察有无血管并发症情况下这些参数的变化。

设计与方法

采用酶联免疫吸附测定法(ELISA)检测MPO、MMP-9和TIMP-1水平。通过分光光度法检测PON1活性。采用双底物法计算PON1表型。

结果

与无血管并发症的患者(无血管并发症患者;NVC)相比,有血管并发症(VC)的患者MPO和TIMP-1水平显著更高(分别为728(367.25 - 1177.90)mg/ml对315.9(176.05 - 687.40)mg/ml;p<0.001;以及172.7(157.7 - 197.7)ng/ml对152.6(129.3 - 172.3)ng/ml;p<0.0001)。MPO水平与PON1芳基酯酶活性呈显著负相关(全患者组(W):r = 0.42,p<0.0001;VC组:r = 0.44,p = 0.01;NVC组:r = 0.39,p<0.0001),与MMP-9呈正相关(W:r = 0.37,p<0.0001;VC组:r = 0.29,p = 0.07;NVC组:r = 0.42,p<0.0001),与TIMP-1也呈正相关(W:r = 0.42,p<0.0001;VC组:r = 0.33,p<0.05;NVC组:r = 0.41,p<0.0001)。在全患者组中,PON1芳基酯酶活性是MPO水平的独立预测因子(β = -0.350,p<0.0001),在有或无心血管并发症的亚组中分别进行研究时也是如此(VC组:β = -0.57, p<0.05;NVC组:β = -0.33, p<0.0001)。

结论

我们的结果表明,同时检测MPO、MMP-9和TIMP-1水平以及PON1芳基酯酶活性可能是动脉粥样硬化更准确的指标,这可能有助于早期治疗,从而提高治疗效果。

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