Circulating and PBMC Lp-PLA2 Associate Differently with Oxidative Stress and Subclinical Inflammation in Nonobese Women (Menopausal Status)

Yangsoo Jang,Tae-Sook Jeong,Gary Sweeney,Philippe Rouet,Yonghee Lee,Ji Young Kim,Jong Ho Lee,Oh Yoen Kim,Jean Kyung Paik

doi:10.1371/journal.pone.0029675

Abstract

BackgroundThis study aimed to determine the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in circulation and peripheral blood mononuclear cells (PBMCs) with inflammatory and oxidative stress markers in nonobese women and according to menopausal status. Lp-PLA2 activity, a marker for cardiovascular risk is associated with inflammation and oxidative stress.Methodology/Principal FindingsEighty postmenopausal women (53.0±4.05 yr) and 96 premenopausal women (39.7±9.25 yr) participated in this study. Lp-PLA2 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-PLA2 activity positively correlated with Lp-PLA2 activity in PBMCs and plasma ox-LDL. In premenopausal women, Lp-PLA2 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-PLA2 activity in the plasma but not the PBMCs was found in the high ox-LDL subgroup. Plasma Lp-PLA2 activity positively correlated with unstimulated PBMC Lp-PLA2 activity in the low ox-LDL subgroup (r = 0.627, P<0.001), whereas in the high ox-LDL circulating Lp-PLA2 activity positively correlated with plasma ox-LDL (r = 0.390, P = 0.014) but not with Lp-PLA2 activity in PBMCs.Conclusions/SignificanceThe lack of relation between circulating Lp-PLA2 activity and Lp-PLA2 activity in PBMCs was found in postmenopausal women with high ox-LDL. This may indicate other sources of circulating Lp-PLA2 activity except PBMC in postmenopausal women with high ox-LDL. We also demonstrated that circulating Lp-PLA2 and PBMC secreted Lp-PLA2 associate differently with markers of oxidative stress and sub clinical inflammation in nonobese women, particularly according to the menopausal states.

Highlights

We demonstrated that circulating Lp-PLA2 and peripheral blood mononuclear cells (PBMCs) secreted LpPLA2 associate differently with markers of oxidative stress and sub clinical inflammation in nonobese women, according to the menopausal states
Lipoprotein-associated phospholipase A2 (Lp-PLA2), known as plasma platelet activating factor acetylhydrolase (PAF-AH), is unique among members of the phospholipase A2 superfamily due to its origin, its association with circulating lipoproteins, and its substrate preference for polar phospholipids, including those generated during the oxidation of low-density lipoprotein (LDL) [1]
The major finding of this study is the lack of relation between circulating Lp-PLA2 activity and Lp-PLA2 activity in PBMCs in postmenopausal women with high oxidized LDL (ox-LDL) ($48.715 U/L, above median)

Summary

Introduction

Lipoprotein-associated phospholipase A2 (Lp-PLA2), known as plasma platelet activating factor acetylhydrolase (PAF-AH), is unique among members of the phospholipase A2 superfamily due to its origin, its association with circulating lipoproteins, and its substrate preference for polar phospholipids, including those generated during the oxidation of low-density lipoprotein (LDL) [1]. Wang et al [21] reported the stimulatory effect of ox-LDL on the expression of Lp-PLA2 in monocytes, which are a primary source of this enzyme. These recent findings in animal and in vitro studies may provide insight into the interaction between Lp-PLA2 activity and oxidative stress in the context of atherosclerosis. Our aim was to study the relationship of Lp-PLA2 activity in plasma and the enzyme activity in supernatants from nonstimulated peripheral blood mononuclear cell (PBMC) cultures. This study aimed to determine the association of lipoprotein-associated phospholipase A2 (Lp-PLA2) activity in circulation and peripheral blood mononuclear cells (PBMCs) with inflammatory and oxidative stress markers in nonobese women and according to menopausal status. Lp-PLA2 activity, a marker for cardiovascular risk is associated with inflammation and oxidative stress

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