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

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

Variability of serial lipoprotein-associated phospholipase A2 measurements in post myocardial infarction patients: Results from the AIRGENE Study Center Augsburg.

Of the numerous emerging biomarkers for coronary heart disease (CHD), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an enzyme involved in lipid metabolism and inflammatory pathways, seems to be a promising candidate. Implementation of Lp-PLA(2) measurement into clinical practice, however, requires data on the reliability of such measurements. METHODS: We measured Lp-PLA(2) concentrations by ELISA in blood samples drawn from 200 post-myocardial infarction patients (39-76 years) at 6 monthly intervals between May 2003 and February 2004, for a total of 1143 samples. We estimated analytical, within-individual, and between-individual variation, the critical difference, and the intraclass correlation coefficient of reliability (ICC) to assess the reliability of serial Lp-PLA(2) measurements. RESULTS: The mean (SD) plasma Lp-PLA(2) concentration for the study participants was 188.7 (41.8) microg/L, with no significant difference between men and women. The analytical CV for Lp-PLA(2) was 4.4%, the within-individual biological CV was 15%, and the between-individual CV was 22%. The ICC was 0.66. An important part of the total variation in plasma Lp-PLA(2) concentration was explained by the between-individual variation (as a percentage of the total variance, 66.1%), whereas the within-individual variance was 31.3%. The analytical variance was as low as 2.6%. CONCLUSIONS: Between-individual variation in Lp-PLA(2) concentration was substantially greater than within-individual variation. In general, our data demonstrate considerable stability and good reproducibility of serial Lp-PLA(2) measurements, results that compared favorably with those for the more commonly measured lipid markers