Prehypertension-associated elevation in circulating lysophosphatidlycholines, Lp-PLA2 activity, and oxidative stress

Abstract

Objective: Prehypertension is a risk factor for atherosclerosis. We investigated alterations in plasma metabolites that are associated with prehypertension.Design, Participants, and Methods: A group of 53 individuals was identified who remained within the range of prehypertension [systolic blood pressure (SBP), 130139 mm Hg; diastolic blood pressure (DBP), 8094 mm Hg] during repeated measurements in a 3-year period. This group was compared with the control group of 53 normotensive subjects (SBP < 120 mm Hg, and DBP < 80 mm Hg) who were matched for age and gender. Metabolomic profiles were analyzed with UPLC-LTQ-Orbitrap mass spectrometry.Results: The prehypertensive group showed higher levels of lysophosphatidylcholines (lysoPCs) containing C14:0, C16:1, C16:0, C18:2, C18:1, C18:0, C20:5, C20:4, C20:3, and C22:6, higher circulating Lp-PLA2 activity, oxidized LDL (ox-LDL), interleukin 6 (IL-6), urinary 8-epi-PGF2α, and higher brachial-ankle pulse wave velocity (ba-PWV),before and after adjusting for BMI, WHR, smoking, alcohol consumption, serum lipid profiles, glucose, and insulin. LysoPC (16:0) was the most important plasma metabolite for evaluating the difference between control and prehypertensive groups, with a variable important in the projection (VIP) value of 17.173, and it showed a positive and independent association with DBP and SBP. In the prehypertensive group, the levels of lysoPC (16:0) positively and significantly correlated with ox-LDL, Lp-PLA2 activity, 8-epi-PGF2α, ba-PWV, and IL-6 before and after adjusting for confounding variables.Conclusions: Prehypertension-associated elevations in lysoPCs, Lp-PLA2 activity, ox-LDL, urinary 8-epi-PGF2α, IL-6, and ba-PWV could indicate increased oxidative stress from Lp-PLA2-catalyzed PC hydrolysis during increased LDL oxidation, thereby enhancing proinflammation and arterial stiffness