α-Tocopherol transfer protein mediates protective hypercapnia in murine ventilator-induced lung injury

Otulakowski, Gail; Engelberts, Doreen; Arima, Hisatomi; Hirate, Hiroyuki; Bayır, Hülya; Post, Martin; Kavanagh, Brian P.

doi:10.1136/thoraxjnl-2016-209501

Cited by 14 publications

(15 citation statements)

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“…Based on a well-defined animal model, we performed whole transcriptome analysis to determine the potential molecular mechanisms in lung pathophysiology post-ventilation. Previously, transcriptomics was performed to explore the potential mechanisms of VILI, or protective ventilation use against VILI at a genetic level [ 36 , 37 ]. Different from the previous analyses, the current study did not solely focus on studying dysregulated genes or pathways involved in the early stage of VILI.…”

Section: Discussionmentioning

confidence: 99%

Landscape of transcription and long non-coding RNAs reveals new insights into the inflammatory and fibrotic response following ventilator-induced lung injury

Wang

Zhang

et al. 2018

Respir Res

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BackgroundMechanical ventilation can cause ventilator-induced lung injury (VILI) and lung fibrosis; however, the underlying mechanisms are still not fully understood. RNA sequencing is a powerful means for detecting vitally important protein-coding transcripts and long non-coding RNAs (lncRNAs) on a genome-wide scale, which may be helpful for reducing this knowledge gap.MethodsNinety C57BL/6 mice were subjected to either high tidal volume ventilation or sham operation, and then mice with ventilation were randomly allocated to periods of recovery for 0, 1, 3, 5, 7, 14, 21, or 28 days. Lung histopathology, wet-to-dry weight ratio, hydroxyproline concentration, and transforming growth factor beta 1 (TGF-β1) levels were determined to evaluate the progression of inflammation and fibrosis. To compare sham-operated lungs, and 0- and 7-day post-ventilated lungs, RNA sequencing was used to elucidate the expression patterns, biological processes, and functional pathways involved in inflammation and fibrosis.ResultsA well-defined fibrotic response was most pronounced on day 7 post-ventilation. Pairwise comparisons among the sham and VILI groups showed a total of 1297 differentially expressed transcripts (DETs). Gene Ontology analysis determined that the stimulus response and immune response were the most important factors involved in inflammation and fibrosis, respectively. Kyoto Encyclopedia of Genes and Genomes analysis revealed that mechanistic target of rapamycin (mTOR), Janus kinase-signal transducer and activator of transcription (JAK/STAT), and cyclic adenosine monophosphate (cAMP) signaling were implicated in early inflammation; whereas TGF-β, hypoxia inducible factor-1 (HIF-1), Toll-like receptor (TLR), and kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathways were significantly involved in subsequent fibrosis. Additionally, 332 DE lncRNAs were identified and enriched in the processes of cellular and biological regulation. These lncRNAs may potentially regulate fibrosis through signaling pathways such as wingless/integrase-1 (Wnt), HIF-1, and TLR.ConclusionsThis is the first transcriptome study to reveal all of the transcript expression patterns and critical pathways involved in the VILI fibrotic process based on the early inflammatory state, and to show the important DE lncRNAs regulated in inflammation and fibrosis. Together, the results of this study provide novel perspectives into the potential molecular mechanisms underlying VILI and subsequent fibrosis.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0822-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Landscape of transcription and long non-coding RNAs reveals new insights into the inflammatory and fibrotic response following ventilator-induced lung injury

Wang

Zhang

et al. 2018

Respir Res

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“…γ-tocopherol has much less affinity (α-tocopherol = 100%, γ-tocopherol = 9% [ 42 ]) for α-TTP and is largely metabolized in the liver and secreted in the bile [ 43 ]. Experimental evidence indicates that α-TTP activity is modulated by oxidative stress potentially influencing vitamin E status [ 44 , 45 , 46 , 47 ].…”

Section: Discussionmentioning

confidence: 99%

Association of Vitamin E Levels with Metabolic Syndrome, and MRI-Derived Body Fat Volumes and Liver Fat Content

et al. 2017

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We aimed to relate circulating α- and γ-tocopherol levels to a broad spectrum of adiposity-related traits in a cross-sectional Northern German study. Anthropometric measures were obtained, and adipose tissue volumes and liver fat were quantified by magnetic resonance imaging in 641 individuals (mean age 61 years; 40.6% women). Concentrations of α- and γ-tocopherol were measured using high performance liquid chromatography. Multivariable-adjusted linear and logistic regression were used to assess associations of circulating α- and γ-tocopherol/cholesterol ratio levels with visceral (VAT) and subcutaneous adipose tissue (SAT), liver signal intensity (LSI), fatty liver disease (FLD), metabolic syndrome (MetS), and its individual components. The α-tocopherol/cholesterol ratio was positively associated with VAT (β scaled by interquartile range (IQR): 0.036; 95%Confidence Interval (CI): 0.0003; 0.071) and MetS (Odds Ratio (OR): 1.83; 95% CI: 1.21–2.76 for 3rd vs. 1st tertile), and the γ-tocopherol/cholesterol ratio was positively associated with VAT (β scaled by IQR: 0.066; 95% CI: 0.027; 0.104), SAT (β scaled by IQR: 0.048; 95% CI: 0.010; 0.087) and MetS (OR: 1.87; 95% CI: 1.23–2.84 for 3rd vs. 1st tertile). α- and γ-tocopherol levels were positively associated with high triglycerides and low high density lipoprotein cholesterol levels (all Ptrend < 0.05). No association of α- and γ-tocopherol/cholesterol ratio with LSI/FLD was observed. Circulating vitamin E levels displayed strong associations with VAT and MetS. These observations lay the ground for further investigation in longitudinal studies.

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“…Myeloperoxidase activity is an index of neutrophil accumulation. The influence of MAE on MPO activity in lung tissues was measured according to the method described by Bradley et al [ 19 , 20 ]. The assay mixture consisted of 0.3 mL 0.1 M phosphate buffer (pH 6.0), 0.3 mL 0.01 M H 2 O 2 , 0.5 mL 0.02 M o-dianisidine (freshly prepared) in deionized water, and 10 μ L lung homogenate supernatant in a final volume of 3.0 mL.…”

Section: Methodsmentioning

confidence: 99%

Antipleuritic and Vascular Permeability Inhibition of the Ethyl Acetate-Petroleum Ether Stem Bark Extract ofMaerua angolensisDC (Capparaceae) in Murine

Ampadu

Boakye‐Gyasi

Osafo

et al. 2018

International Journal of Inflammation

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Maerua angolensis has been used traditionally in the management of pain, arthritis, and rheumatism in Ghana and Nigeria but no scientific evidence is currently available to give credence to its folkloric use. The aim of this study was therefore to evaluate the anti-inflammatory effects of a stem bark extract of Maerua angolensis DC (MAE) in acute inflammatory models. The effects of MAE (30-300 mg kg−1) on neutrophil infiltration, exudate volume, and endogenous antioxidant enzymes in lung tissues and lung morphology were evaluated with the carrageenan induced pleurisy model in Sprague Dawley rats. The effects of MAE (30-300 mg kg−1) on vascular permeability were also evaluated in the acetic acid induced vascular permeability in ICR mice. MAE significantly reduced neutrophil infiltration, exudate volume, and lung tissue damage in carrageenan induced pleurisy. MAE increased the activities of antioxidant enzymes glutathione, superoxide dismutase, and catalase in lung tissues. The extract was also able to reduce myeloperoxidase activity and lipid peroxidation in lung tissues in carrageenan induced rat pleurisy. Vascular permeability was also attenuated by the extract with marked reduction of Evans blue dye leakage in acetic acid induced permeability assay. The results indicated that Maerua angolensis is effective in ameliorating inflammation induced by carrageenan and acetic acid. It also has the potential of increasing the activity of endogenous antioxidant enzymes.

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α-Tocopherol transfer protein mediates protective hypercapnia in murine ventilator-induced lung injury

Abstract: Inspired CO upregulates αTTP which increases lung α-tocopherol levels and inhibits synthesis of a pathogenic chemoattractant.

Cited by 14 publications

References 41 publications

Landscape of transcription and long non-coding RNAs reveals new insights into the inflammatory and fibrotic response following ventilator-induced lung injury

Landscape of transcription and long non-coding RNAs reveals new insights into the inflammatory and fibrotic response following ventilator-induced lung injury

Association of Vitamin E Levels with Metabolic Syndrome, and MRI-Derived Body Fat Volumes and Liver Fat Content

Antipleuritic and Vascular Permeability Inhibition of the Ethyl Acetate-Petroleum Ether Stem Bark Extract ofMaerua angolensisDC (Capparaceae) in Murine

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