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脂蛋白相关磷脂酶A2活性与冠状动脉疾病及氧化应激标志物相关:一项病例对照研究。

Lipoprotein-associated phospholipase A2 activity is associated with coronary artery disease and markers of oxidative stress: a case-control study.

作者信息

Kim Ji Young, Hyun Yae Jung, Jang Yangsoo, Lee Byoung Kwon, Chae Jey Sook, Kim So Eui, Yeo Hyun Yang, Jeong Tae-Sook, Jeon Dong Woon, Lee Jong Ho

机构信息

Yonsei University Research Institute of Science for Aging, Yonsei University, Seoul, Korea.

出版信息

Am J Clin Nutr. 2008 Sep;88(3):630-7. doi: 10.1093/ajcn/88.3.630.

DOI:10.1093/ajcn/88.3.630
PMID:18779277
Abstract

BACKGROUND

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a lipoprotein-bound enzyme that can release atherogenic isoprostanes from esterified phospholipids and that may be involved in inflammation and atherosclerosis.

OBJECTIVE

This study investigates the association between Lp-PLA(2) activity and coronary artery disease (CAD) in relation to oxidative stress markers, in particular urinary 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)).

DESIGN

We conducted a case-control study in which the cross-sectional relation between Lp-PLA(2) activity, lipoproteins, and oxidative stress markers was determined in 799 patients with angiographically confirmed CAD and 925 healthy controls.

RESULTS

Lp-PLA(2) activity was significantly (P < 0.001) higher in CAD cases than in controls (32.9 +/- 0.46 and 29.7 +/- 0.42 nmol . mL(-1) . min(-1), respectively). Both elevated Lp-PLA(2) activity and urinary excretion concentrations of 8-epi-PGF(2alpha) were associated with greater CAD risk (P for trend < 0.001). Odds ratios for the upper quartiles of Lp-PLA(2) activity and 8-epi-PGF(2alpha).excretion were 2.47 (95% CI: 1.79, 3.40) and 2.19 (1.52, 3.15), respectively, after adjustment for sex, age, BMI, blood pressure, smoking and alcohol consumption status, and LDL and HDL cholesterol. When we examined the additive effect of both markers for CAD risk, the relation between 8-epi-PGF(2alpha) and CAD was weakened above the second quartile of Lp-PLA(2) activity. Moreover, Lp-PLA(2) activity was positively correlated with urinary excretion concentrations of 8-epi-PGF(2alpha) in controls (r = 0.277, P < 0.001) and cases (r = 0.202, P < 0.001) and with the tail moment of lymphocyte DNA (r = 0.213, P < 0.001) in controls.

CONCLUSION

This study shows an association of elevated Lp-PLA(2) activity with CAD risk in relation to oxidant stress and thus supports a proatherogenic role of Lp-PLA(2).

摘要

背景

脂蛋白相关磷脂酶A2(Lp-PLA2)是一种与脂蛋白结合的酶,它可从酯化磷脂中释放出具有致动脉粥样硬化作用的异前列腺素,可能参与炎症和动脉粥样硬化过程。

目的

本研究调查Lp-PLA2活性与冠状动脉疾病(CAD)之间的关联,并分析其与氧化应激标志物,特别是尿8-表-前列腺素F2α(8-epi-PGF2α)的关系。

设计

我们进行了一项病例对照研究,测定了799例经血管造影证实患有CAD的患者和925名健康对照者中Lp-PLA2活性、脂蛋白和氧化应激标志物之间的横断面关系。

结果

CAD患者的Lp-PLA2活性显著高于对照组(P<0.001)(分别为32.9±0.46和29.7±0.42 nmol·mL-1·min-1)。Lp-PLA2活性升高和尿8-epi-PGF2α排泄浓度均与更高的CAD风险相关(趋势P<0.001)。在对性别、年龄、体重指数、血压、吸烟和饮酒状况以及低密度脂蛋白和高密度脂蛋白胆固醇进行校正后,Lp-PLA2活性和8-epi-PGF2α排泄上四分位数的比值比分别为2.47(95%CI:1.79,3.40)和2.19(1.52,3.15)。当我们检查这两种标志物对CAD风险的相加作用时,在Lp-PLA2活性高于第二个四分位数时,8-epi-PGF2α与CAD之间的关系减弱。此外,在对照组(r = 0.277,P<0.001)和病例组(r = 0.202,P<0.001)中,Lp-PLA2活性与尿8-epi-PGF2α排泄浓度呈正相关,在对照组中与淋巴细胞DNA的尾矩呈正相关(r = 0.213,P<0.001)。

结论

本研究表明,Lp-PLA2活性升高与CAD风险增加有关,且与氧化应激有关,因此支持Lp-PLA2在动脉粥样硬化发生中的促动脉粥样硬化作用。

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