The lipid biology of sepsis

Amunugama, Kaushalya; Pike, Daniel P.; Ford, David A.

doi:10.1016/j.jlr.2021.100090

Cited by 45 publications

(41 citation statements)

References 230 publications

(219 reference statements)

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“…This complex system culminates in life-threatening organ injury and metabolic derangements ( Chuang et al, 2006 ; Robertson and Coopersmith, 2006 ; Galley, 2011 ; Angus and van der Poll, 2013 ; Delano and Ward, 2016 ; Singer et al, 2016 ; Prauchner, 2017 ). Lipids and lipid-related signaling pathways have been investigated as mediators, potentially at the blood-endothelial interface during sepsis ( Amunugama et al, 2021a ). Specific lipids may also have prognostic value as biomarkers in sepsis ( Meyer et al, 2017 ; Mecatti et al, 2018 ; Mecatti et al, 2020 ; Wang et al, 2020 ; Amunugama et al, 2021a ).…”

Section: Introductionmentioning

confidence: 99%

“…Lipids and lipid-related signaling pathways have been investigated as mediators, potentially at the blood-endothelial interface during sepsis ( Amunugama et al, 2021a ). Specific lipids may also have prognostic value as biomarkers in sepsis ( Meyer et al, 2017 ; Mecatti et al, 2018 ; Mecatti et al, 2020 ; Wang et al, 2020 ; Amunugama et al, 2021a ). Additionally, a major cause of COVID-19 mortality is sepsis-associated acute respiratory distress syndrome (ARDS).…”

Section: Introductionmentioning

confidence: 99%

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Plasmalogen Loss in Sepsis and SARS-CoV-2 Infection

Pike

McGuffee

Geerling

et al. 2022

Front. Cell Dev. Biol.

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Plasmalogens are plasma-borne antioxidant phospholipid species that provide protection as cellular lipid components during cellular oxidative stress. In this study we investigated plasma plasmalogen levels in human sepsis as well as in rodent models of infection. In humans, levels of multiple plasmenylethanolamine molecular species were decreased in septic patient plasma compared to control subject plasma as well as an age-aligned control subject cohort. Additionally, lysoplasmenylcholine levels were significantly decreased in septic patients compared to the control cohorts. In contrast, plasma diacyl phosphatidylethanolamine and phosphatidylcholine levels were elevated in septic patients. Lipid changes were also determined in rats subjected to cecal slurry sepsis. Plasma plasmenylcholine, plasmenylethanolamine, and lysoplasmenylcholine levels were decreased while diacyl phosphatidylethanolamine levels were increased in septic rats compared to control treated rats. Kidney levels of lysoplasmenylcholine as well as plasmenylethanolamine molecular species were decreased in septic rats. Interestingly, liver plasmenylcholine and plasmenylethanolamine levels were increased in septic rats. Since COVID-19 is associated with sepsis-like acute respiratory distress syndrome and oxidative stress, plasmalogen levels were also determined in a mouse model of COVID-19 (intranasal inoculation of K18 mice with SARS-CoV-2). 3 days following infection, lung infection was confirmed as well as cytokine expression in the lung. Multiple molecular species of lung plasmenylcholine and plasmenylethanolamine were decreased in infected mice. In contrast, the predominant lung phospholipid, dipalmitoyl phosphatidylcholine, was not decreased following SARS-CoV-2 infection. Additionally total plasmenylcholine levels were decreased in the plasma of SARS-CoV-2 infected mice. Collectively, these data demonstrate the loss of plasmalogens during both sepsis and SARS-CoV-2 infection. This study also indicates plasma plasmalogens should be considered in future studies as biomarkers of infection and as prognostic indicators for sepsis and COVID-19 outcomes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Plasmalogen Loss in Sepsis and SARS-CoV-2 Infection

Pike

McGuffee

Geerling

et al. 2022

Front. Cell Dev. Biol.

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“…When exposed to diverse stimuli, such as LPS, TNF- α and IFN- γ , M1 macrophages are activated, and intracellular inflammatory and metabolic reprogramming pathways are activated, including STAT1, NF-κB and HIF-1 α axes, eventually promoting the generation of plentiful cytokines that damage cardiomyocytes and then induce cardiac dysfunction ( Y. Liu et al, 2017 ; Chen et al, 2021 ). Moreover, other bioactive factors, such as PGE2, TXB2 ( Amunugama et al, 2021 ), NO ( Jia et al, 2018 ) and NLRP3 ( Busch et al, 2021 ), are reported to facilitate inflammation progression and tissue injury during the course of sepsis. However, to date, the specific mechanisms responsible for SIC remain elusive.…”

Section: Introductionmentioning

confidence: 99%

“…Liu et al, 2017;Chen et al, 2021). Moreover, other bioactive factors, such as PGE2, TXB2 (Amunugama et al, 2021), NO (Jia et al, 2018) and NLRP3 (Busch et al, 2021), are reported to facilitate inflammation progression and tissue injury during the course of sepsis. However, to date, the specific mechanisms responsible for SIC remain elusive.…”

Section: Introductionmentioning

confidence: 99%

Harmine Alleviated Sepsis-Induced Cardiac Dysfunction by Modulating Macrophage Polarization via the STAT/MAPK/NF-κB Pathway

Ruan

Qin

et al. 2022

Front. Cell Dev. Biol.

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Sepsis is a dysregulated systemic inflammatory response that often leads to cardiac dysfunction, which is termed sepsis-induced cardiomyopathy (SIC). Harmine, a natural β-carboline alkaloid compound, has been shown to exert pharmacological effects on several diseases. Here, we investigated whether harmine protected against SIC development and the underlying mechanisms. In vitro, the expression of the M1 phenotype markers iNOS and COX-2 was increased in RAW 264.7 cells stimulated with lipopolysaccharide (LPS), but this effect was reversed by the harmine intervention. Furthermore, LPS-induced increases in the levels of inflammatory cytokines, including IL-1β, IL-6, TNF-α, iNOS, COX-2, PGE2 and TXB2, generated by macrophages were suppressed when the cells were pretreated with harmine. Meanwhile, our findings showed that harmine administration effectively attenuated inflammation and apoptosis in H9c2 cells in the proinflammatory environment produced by macrophages, as evidenced by reductions in NLRP3 and cleaved caspase 3 levels and the p-NF-κB/NF-κB ratio. The western blot results indicated that the mechanisms underlying harmine-mediated inhibition of M1 polarization might be associated with suppression of STAT1/3, NF-κB and MAPK activation. Furthermore, an LPS injection induced cardiac dysfunction and decreased the survival rate of mice, which were alleviated by harmine treatment, and the relevant mechanism was possibly attributed to a drug-induced attenuation of the inflammatory and apoptotic processes in cardiomyocytes. Collectively, these results implied that harmine treatment protected against SIC by suppressing M1 phenotypic polarization and inflammation in macrophages.

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“…Some clinical markers, such as procalcitonin (PCT) and C-reactive protein (CRP), have predictive value for septic prognosis, but their specificity or sensitivity are significantly limited by the clinical and pathogenetic heterogeneities of sepsis ( 4 ). Of note, the increasing lipidomic studies indicate that lipid metabolism remodeling plays roles in septic pathophysiology ( 5 ). Given that most alterations in cellular function, inflammatory response and energy imbalance during sepsis could lead to the changes in lipid metabolism, the lipids biomarkers show advantages in prognosis of septic patients ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

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

Luo

Shi

et al. 2022

Front. Immunol.

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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.

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The lipid biology of sepsis

Cited by 45 publications

References 230 publications

Plasmalogen Loss in Sepsis and SARS-CoV-2 Infection

Plasmalogen Loss in Sepsis and SARS-CoV-2 Infection

Harmine Alleviated Sepsis-Induced Cardiac Dysfunction by Modulating Macrophage Polarization via the STAT/MAPK/NF-κB Pathway

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

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