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

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.

Lysophosphatidylcholine and Carotid Intima-Media Thickness in Young Smokers: A Role for Oxidized LDL-Induced Expression of PBMC Lipoprotein-Associated Phospholipase A2?

“…In this study we also demonstrated a positive correlation between mRNA expression of Lp-PLA2 in PBMC and plasma Lp-PLA2 levels in all the subjects; this finding is in line with a recent study showing that in non-obese women plasma Lp-PLA2 activity positively correlated with PBMC Lp-PLA2 activity [37]. Moreover, given the strong association between carotid and coronary atherosclerosis [12,13], the evidence that in no subject carotid plaques were detected, supports the conclusion that PBMC are a major source of Lp-PLA2 in our young healthy subjects.…”

Atypical Antipsychotic Administration in Schizophrenic Patients Leads to Elevated Lipoprotein‐Associated Phospholipase A2 Levels and Increased Cardiovascular Risk: A Retrospective Cohort Study

“…Fat accumulation is the reason of the increased Lp‐PLA2 levels in high BMI patients. Visceral fat accumulation plays important roles in LDL atherogenicity including increased LDL oxidation and smaller LDL particle size, and oxidative stress activating inflammation and cytokine expression . Ox‐LDL stimulates Lp‐PLA2 expression in monocytes through the phosphatidylinositol 3‐kinase and p38 mitogen‐activating protein kinase pathways .…”

Oxidative damage and the pathogenesis of menopause related disturbances and diseases

“…To better clarify this issue we critically review the results of the nine largest studies comparing OxS in reproductive age and postmenopausal women. In three studies urinary F2-iso was measured by ELISA [75,116,119], eventually including a chromatographic pre-analytical step to improve the specificity of detection. Notably these studies failed to detect an increase in F2-isos in postmenopausal women compared to younger fertile counterparts.…”