The Levels of Oxidized Phospholipids in High-Density Lipoprotein During the Course of Sepsis and Their Prognostic Value

Abstract

PurposeTo examine the levels of 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero phosphatidylcholine (POVPC) and 1-palmitoyl-2-glutaroyl-sn-glycero-phosphatidylcholine (PGPC) (the oxidized phosphatidylcholines) in HDL during the course of sepsis and to evaluate their prognostic value.Materials and MethodsThis prospective cohort pilot study enrolled 25 septic patients and 10 healthy subjects from 2020 to 2021. The HDLs were extracted from patient plasmas at day 1, 3 and 7 after sepsis onset and from healthy plasmas (total 81 plasma samples). These HDLs were then subjected to examining POVPC and PGPC by using an ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) system. We further measured the levels of 38 plasma cytokines by Luminex and evaluated the correlation of HDL-POVPC level with these cytokines. Patients were further stratified into survivors and non-survivors to analyze the association of HDL-POVPC level with 28-day mortality.ResultsSeptic patients exhibited significant increase of HDL-POVPC at day 1, 3 and 7 after sepsis onset (POVPC-D1, p=0.0004; POVPC-D3, p=0.033; POVPC-D7, p=0.004, versus controls). HDL-PGPC was detected only in some septic patients (10 of 25) but not in healthy controls. Septic patients showed a significant change of the plasma cytokines profile. The correlation assay showed that IL-15 and IL-18 levels were positively correlated with HDL-POVPC level, while the macrophage-derived chemokine (MDC) level was negatively correlated with HDL-POVPC level. Furthermore, HDL-POVPC level in non-survivors was significantly increased versus survivors at day 1 and 3 (POVPC-D1, p=0.002; POVPC-D3, p=0.003). Area under ROC curves of POVPC-D1 and POVPC-D3 in predicting 28-day mortality were 0.828 and 0.851. POVPC-D1and POVPC-D3 were the independent risk factors for the death of septic patients (p=0.046 and 0.035).ConclusionsHDL-POVPC was persistently increased in the course of sepsis. POVPC-D1 and POVPC-D3 were significantly correlated with 28-mortality and might be valuable to predict poor prognosis.

The oxidized phospholipid PGPC impairs endothelial function by promoting endothelial cell ferroptosis via FABP3

“…There was an EPIC Norfolk study that proved levels of oxidized phospholipids in plasma are associated with an increased risk of coronary artery disease (CAD) ( 45 ). The studies showed that the total phospholipid level in the plasma of patients is higher than that in the plasma of healthy individuals ( 46 ). Previous studies have shown that PGPC concentrations in plasma from healthy controls range from 0.15 to 1 μM ( 47 , 48 ).…”

Circulating protein and lipid markers of early sepsis diagnosis and prognosis: a scoping review

“…No sample size limit was included due to limited literature. Biomarkers are presented in order of relative abundance in literature.bHDL level was measured as HDL associated cholesterol (HDL-C) in studies [93–96,98 ▪▪ ,101–103]. Other HDL quantification was assayed using various metabolomic methods.cLDL level was measured as LDL associated cholesterol (LDL-C) in studies [93,96,98 ▪▪ ,101].…”

“…HDL is involved in immune modulation through its binding and sequestration of bacterial lipopolysaccharide (LPS), reducing integrin activation on monocytes and neutrophils, and protecting the endothelium by modulating vascular tone [113 & ]. HDL can be quantified biochemically as HDL associated cholesterol (HDL-C) [93][94][95][96]98 && , [101][102][103] or by mass spectrometry [90,97]. HDL levels decline at the time of hospital admission in patients with sepsis [93][94][95][96][97][98][99] and are lower in critically ill patients with sepsis relative to those critically ill due to trauma [96] or critically ill due to a nonsepsis diagnosis [99].…”

“…bHDL level was measured as HDL associated cholesterol (HDL-C) in studies [93–96,98 ▪▪ ,101–103]. Other HDL quantification was assayed using various metabolomic methods.…”

“…Alteration in HDL particle size, composition, structure, and function is implicated in sepsis and may assist with its diagnosis. HDL particles increase in size [93] and are more oxidized [102 ▪ ][103], as demonstrated by the presence of more 1-palmitoyl-2-(5-oxovaleroyl)- sn -glycero-phosphatidylcholine (HDL-POVPC), which is associated with greater mortality [102 ▪ ]. The HDL inflammatory index established to quantify HDL's protective role against LDL-associated inflammation is increased in sepsis, suggesting that HDL particles become dysfunctional [103].…”