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

Lipoprotein associated phospholipase A2: role in atherosclerosis and utility as a biomarker for cardiovascular risk

Atherosclerosis and its clinical manifestations are widely prevalent throughout the world. Atherogenesis is highly complex and modulated by numerous genetic and environmental risk factors. A large body of basic scientific and clinical research supports the conclusion that inflammation plays a significant role in atherogenesis along the entire continuum of its progression. Inflammation adversely impacts intravascular lipid handling and metabolism, resulting in the development of macrophage foam cell, fatty streak, and atheromatous plaque formation. Given the enormous human and economic cost of myocardial infarction, ischemic stroke, peripheral arterial disease and amputation, and premature death and disability, considerable effort is being committed to refining our ability to correctly identify patients at heightened risk for atherosclerotic vascular disease and acute cardiovascular events so that they can be treated earlier and more aggressively. Serum markers of inflammation have emerged as an important component of risk factor burden. Lipoprotein-associated phospholipase A2 (Lp-PLA2) potentiates intravascular inflammation and atherosclerosis. A variety of epidemiologic studies support the utility of Lp-PLA2 measurements for estimating and further refining cardiovascular disease risk. Drug therapies to inhibit Lp-PLA2 are in development and show considerable promise, including darapladib, a specific molecular inhibitor of the enzyme. In addition to substantially inhibiting Lp-PLA2 activity, darapladib reduces progression of the necrotic core volume of human coronary artery atheromatous plaque. The growing body of evidence points to an important role and utility for Lp-PLA2 testing in preventive and personalized clinical medicine