Circulating and PBMC Lp-PLA 2 associate differently with oxidative stress and subclinical inflammation in nonobese women (menopausal status)

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.