Prehypertension-Associated Elevation in Circulating Lysophosphatidlycholines, Lp-PLA2 Activity, and Oxidative Stress

Abstract

Prehypertension is a risk factor for atherosclerosis. We investigated alterations in plasma metabolites that are associated with prehypertension. A group of 53 individuals was identified who remained within the range of prehypertension during repeated measurements in a 3-year period. This group was compared with the control group of 53 normotensive subjects who were matched for age and gender. Metabolomic profiles were analyzed with UPLC-LTQ-Orbitrap mass spectrometry. 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. 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.

Energy Intake and Plasma Adiponectin as Potential Determinants of Lipoprotein‐Associated Phospholipase A2 Activity: A Cross‐Sectional Study

“…No significant differences were observed across Lp‐PLA 2 activity quartiles with reference to history of dyslipidemia or hypertension. Our results are in agreement with previous studies among overweight and obese subjects (Jackisch et al, ; Steffen et al, ), subjects with dyslipidemia (Tellis et al, ) and apparently healthy subjects with prehypertension (Kim et al, ). Higher Lp‐PLA 2 activity could be explained by higher Lp‐PLA 2 mass concurrently with higher levels of total and LDL‐cholesterol, triacylglycerols, and apolipoprotein B in obese compared to nonobese subjects and in subjects with dyslipidemia compared to subjects with normal lipid levels (Barakat et al, ; Jackisch et al, ; Tellis et al, ).…”

Synergistic therapeutic effects of Duzhong Jiangya Tablets and amlodipine besylate combination in spontaneously hypertensive rats using 1H‐NMR‐ and MS‐based metabolomics

“…It affects endothelium‐dependent relaxation by stimulating monocytes to produce tumor necrosis factor‐α, interleukin‐1β, and interleukin‐6 in a dose‐ and time‐dependent manner (Jim, Hung, Yoo, Kim, & Sok, ; Kim et al, ; Liuwu, Hurtcamejo, & Wiklund, ). At the same time, elevated LysoPCs are associated with oxidative stress, thereby increasing inflammation and arterial stiffness (Kim, Jung, Kim, Lee, & Lee, ). According to our results, the levels of serine, LysoPC (16:0), and LysoPC (18:1) increased, and the content of choline decreased in SHR, suggesting that the synthesis of choline in the body increased and was converted into LysoPCs.…”

Oleoyl-Lysophosphatidylcholine Limits Endothelial Nitric Oxide Bioavailability by Induction of Reactive Oxygen Species

“…The relevance of our data obtained in cell culture and aortic rings for human cardiovascular pathophysiology is highlighted by a most recent report on increased LPC 18:1 plasma levels in prehypertensive patients compared with normotensive controls [57].…”