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循环和 PBMC Lp-PLA2 在非肥胖女性(绝经状态)中与氧化应激和亚临床炎症的关联不同。

Circulating and PBMC Lp-PLA2 associate differently with oxidative stress and subclinical inflammation in nonobese women (menopausal status).

机构信息

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

出版信息

PLoS One. 2012;7(2):e29675. doi: 10.1371/journal.pone.0029675. Epub 2012 Feb 16.

Abstract

BACKGROUND

This study aimed to determine the association of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity in circulation and peripheral blood mononuclear cells (PBMCs) with inflammatory and oxidative stress markers in nonobese women and according to menopausal status. Lp-PLA(2) activity, a marker for cardiovascular risk is associated with inflammation and oxidative stress.

METHODOLOGY/PRINCIPAL FINDINGS: Eighty postmenopausal women (53.0±4.05 yr) and 96 premenopausal women (39.7±9.25 yr) participated in this study. Lp-PLA(2) activities, interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β in plasma as well as in PBMCs were measured. Plasma ox-LDL was also measured. Postmenopausal women demonstrated higher circulating levels of ox-LDL and IL-6, as well as IL-6, TNF-α, and IL-1β in PBMCs, than premenopausal women. In both groups, plasma Lp-PLA(2) activity positively correlated with Lp-PLA(2) activity in PBMCs and plasma ox-LDL. In premenopausal women, Lp-PLA(2) activities in plasma and PBMCs positively correlated with IL-6, TNF-α, and IL-1β in PBMCs. In postmenopausal women, plasma ox-LDL positively correlated with PBMC cytokine production. In subgroup analysis of postmenopausal women according to plasma ox-LDL level (median level: 48.715 U/L), a significant increase in Lp-PLA(2) activity in the plasma but not the PBMCs was found in the high ox-LDL subgroup. Plasma Lp-PLA(2) activity positively correlated with unstimulated PBMC Lp-PLA(2) activity in the low ox-LDL subgroup (r = 0.627, P<0.001), whereas in the high ox-LDL circulating Lp-PLA(2) activity positively correlated with plasma ox-LDL (r = 0.390, P = 0.014) but not with Lp-PLA(2) activity in PBMCs.

CONCLUSIONS/SIGNIFICANCE: The lack of relation between circulating Lp-PLA(2) activity and Lp-PLA(2) activity in PBMCs was found in postmenopausal women with high ox-LDL. This may indicate other sources of circulating Lp-PLA(2) activity except PBMC in postmenopausal women with high ox-LDL. We also demonstrated that circulating Lp-PLA(2) and PBMC secreted Lp-PLA(2) associate differently with markers of oxidative stress and sub clinical inflammation in nonobese women, particularly according to the menopausal states.

摘要

背景

本研究旨在探讨脂蛋白相关磷脂酶 A2(Lp-PLA2)在循环和外周血单核细胞(PBMC)中的活性与非肥胖女性炎症和氧化应激标志物的相关性,并根据绝经状态进行分析。Lp-PLA2 活性是心血管风险的标志物,与炎症和氧化应激有关。

方法/主要发现:本研究纳入了 80 名绝经后女性(53.0±4.05 岁)和 96 名绝经前女性(39.7±9.25 岁)。测量了她们血浆和 PBMC 中的 Lp-PLA2 活性、白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α 和 IL-1β,以及血浆氧化型低密度脂蛋白(ox-LDL)。绝经后女性的循环 ox-LDL 和 IL-6 水平以及 PBMC 中的 IL-6、TNF-α 和 IL-1β 水平均高于绝经前女性。在两组中,血浆 Lp-PLA2 活性与 PBMC 中的 Lp-PLA2 活性和血浆 ox-LDL 均呈正相关。在绝经前女性中,血浆和 PBMC 中的 Lp-PLA2 活性与 PBMC 中的 IL-6、TNF-α 和 IL-1β 呈正相关。在绝经后女性中,血浆 ox-LDL 与 PBMC 细胞因子的产生呈正相关。根据血浆 ox-LDL 水平(中位数:48.715 U/L)对绝经后女性进行亚组分析,发现高 ox-LDL 亚组血浆 Lp-PLA2 活性显著升高,但 PBMC 中 Lp-PLA2 活性没有升高。血浆 Lp-PLA2 活性与低 ox-LDL 亚组中未刺激的 PBMC Lp-PLA2 活性呈正相关(r=0.627,P<0.001),而在高 ox-LDL 循环中,血浆 Lp-PLA2 活性与血浆 ox-LDL 呈正相关(r=0.390,P=0.014),但与 PBMC 中的 Lp-PLA2 活性无关。

结论/意义:在高 ox-LDL 的绝经后女性中,我们发现循环 Lp-PLA2 活性与 PBMC 中的 Lp-PLA2 活性之间缺乏相关性。这可能表明在高 ox-LDL 的绝经后女性中,除了 PBMC 之外,循环 Lp-PLA2 还来自其他来源。我们还表明,在非肥胖女性中,循环 Lp-PLA2 和 PBMC 分泌的 Lp-PLA2 与氧化应激和亚临床炎症标志物的相关性不同,尤其是根据绝经状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1be/3281008/ffdddb8a3198/pone.0029675.g001.jpg

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