Yonsei University Research Institute of Science for Aging, Yonsei University, Seoul, Korea.
PLoS One. 2012;7(2):e29675. doi: 10.1371/journal.pone.0029675. Epub 2012 Feb 16.
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.
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。