Low-molecular-weight heparin reduces hyperoxia-augmented ventilator-induced lung injury via serine/threonine kinase-protein kinase B.

Abstract:

BACKGROUND:High-tidal-volume mechanical ventilation and hyperoxia used in patients with acute lung injury (ALI) can induce the release of cytokines, including high-mobility group box-1 (HMGB1), oxygen radicals, neutrophil infiltration, and the disruption of epithelial and endothelial barriers. Hyperoxia has been shown to increase ventilator-induced lung injury, but the mechanisms regulating interaction between high tidal volume and hyperoxia are unclear. We hypothesized that subcutaneous injections of enoxaparin would decrease the effects of hyperoxia on high-tidal-volume ventilation-induced HMGB1 production and neutrophil infiltration via the serine/threonine kinase/protein kinase B (Akt) pathway. METHODS:Male C57BL/6, either wild type or Akt+/-, aged between 6 and 8 weeks, weighing between 20 and 25 g, were exposed to high-tidal-volume (30 ml/kg) mechanical ventilation with room air or hyperoxia for 2 to 8 hours with or without 4 mg/kg enoxaparin administration. Nonventilated mice served as a control group. Evan blue dye, lung wet-to-dry weight ratio, free radicals, myeloperoxidase, Western blot of Akt, and gene expression of HMGB1 were measured. The expression of HMGB1 was studied by immunohistochemistry. RESULTS:High-tidal-volume ventilation using hyperoxia induced microvascular permeability, Akt activation, HMGB1 mRNA expression, neutrophil infiltration, oxygen radicals, HMGB1 production, and positive staining of Akt in bronchial epithelium. Hyperoxia-induced augmentation of ventilator-induced lung injury was attenuated with Akt deficient mice and pharmacological inhibition of Akt activity by enoxaparin. CONCLUSION:These data suggest that enoxaparin attenuates hyperoxia-augmented high-tidal-volume ventilation-induced neutrophil influx and HMGB1 production through inhibition of the Akt pathway. Understanding the protective mechanism of enoxaparin related with the reduction of HMGB1 may help further knowledge of the effects of mechanical forces in the lung and development of possible therapeutic strategies involved in acute lung injury.

journal_name

Respir Res

journal_title

Respiratory research

authors

Li LF,Yang CT,Huang CC,Liu YY,Kao KC,Lin HC

doi

10.1186/1465-9921-12-90

subject

Has Abstract

pub_date

2011-07-05 00:00:00

pages

90

eissn

1465-9921

issn

1465-993X

pii

1465-9921-12-90

journal_volume

12

pub_type

杂志文章
  • A candidate gene identification strategy utilizing mouse to human big-data mining: "3R-tenet" in COPD genetic research.

    abstract:BACKGROUND:Early life impairments leading to lower lung function by adulthood are considered as risk factors for chronic obstructive pulmonary disease (COPD). Recently, we compared the lung transcriptomic profile between two mouse strains with extreme total lung capacities to identify plausible pulmonary function deter...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-018-0795-y

    authors: Vishweswaraiah S,George L,Purushothaman N,Ganguly K

    更新日期:2018-06-06 00:00:00

  • What have transgenic and knockout animals taught us about respiratory disease?

    abstract::Over the past decade there has been a significant shift to the use of murine models for investigations into the molecular basis of respiratory diseases, including asthma and chronic obstructive pulmonary disease. These models offer the exciting prospect of dissecting the complex interaction between cytokines, chemokin...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审

    doi:10.1186/rr17

    authors: Vasquez YR,Spina D

    更新日期:2000-01-01 00:00:00

  • Local therapy with CpG motifs in a murine model of allergic airway inflammation in IFN-beta knock-out mice.

    abstract:BACKGROUND:CpG oligodeoxynucleotides (CpG-ODN) are capable of inducing high amounts of type I IFNs with many immunomodulatory properties. Furthermore, type-I IFNs have been proposed to play a key role in mediating effects of CpG-ODN. The precise role of IFN-beta in the immunomodulatory effects of CpG-ODN is not known. ...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-6-25

    authors: Matheu V,Treschow A,Teige I,Navikas V,Issazadeh-Navikas S

    更新日期:2005-03-05 00:00:00

  • Maintained inspiratory activity during proportional assist ventilation in surfactant-depleted cats early after surfactant instillation: phrenic nerve and pulmonary stretch receptor activity.

    abstract:BACKGROUND:Inspiratory activity is a prerequisite for successful application of patient triggered ventilation such as proportional assist ventilation (PAV). It has recently been reported that surfactant instillation increases the activity of slowly adapting pulmonary stretch receptors (PSRs) followed by a shorter inspi...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-7-38

    authors: Sindelar R,Rieger-Fackeldey E,Jonzon A,Schaller P,Schulze A,Sedin G

    更新日期:2006-03-10 00:00:00

  • Superoxide dismutase A antigens derived from molecular analysis of sarcoidosis granulomas elicit systemic Th-1 immune responses.

    abstract:BACKGROUND:Sarcoidosis is an idiopathic granulomatous disease with pathologic and immunologic features similar to tuberculosis. Routine histologic staining and culture fail to identify infectious agents. An alternative means for investigating a role of infectious agents in human pathogenesis involves molecular analysis...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-9-36

    authors: Allen SS,Evans W,Carlisle J,Hajizadeh R,Nadaf M,Shepherd BE,Pride DT,Johnson JE,Drake WP

    更新日期:2008-04-25 00:00:00

  • Association of time-to-treatment with outcomes of Pneumocystis pneumonia with respiratory failure in HIV-negative patients.

    abstract:BACKGROUND:The prevalence of pneumocystis pneumonia (PCP) and associated hypoxic respiratory failure is increasing in human immunodeficiency virus (HIV)-negative patients. However, no prior studies have evaluated the effect of early anti-PCP treatment on clinical outcomes in HIV-negative patient with severe PCP. Theref...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-019-1188-6

    authors: Ko RE,Na SJ,Huh K,Suh GY,Jeon K

    更新日期:2019-09-26 00:00:00

  • Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients.

    abstract:BACKGROUND:Cigarette smoke exposure including biologically active lipopolysaccharide (LPS) in the particulate phase of cigarette smoke induces activation of alveolar macrophages (AM) and alveolar epithelial cells leading to production of inflammatory mediators. This represents a crucial mechanism in the pathogenesis of...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-6-68

    authors: Droemann D,Goldmann T,Tiedje T,Zabel P,Dalhoff K,Schaaf B

    更新日期:2005-07-08 00:00:00

  • Rate of progression of CT-quantified emphysema in male current and ex-smokers: a follow-up study.

    abstract:BACKGROUND:Little is known about the factors associated with CT-quantified emphysema progression in heavy smokers. The objective of this study was to investigate the effect of length of smoking cessation and clinical / demographical factors on the rate of emphysema progression and FEV1-decline in male heavy smokers. M...

    journal_title:Respiratory research

    pub_type: 杂志文章,随机对照试验

    doi:10.1186/1465-9921-14-55

    authors: Mohamed Hoesein FA,Zanen P,de Jong PA,van Ginneken B,Boezen HM,Groen HJ,Oudkerk M,de Koning HJ,Postma DS,Lammers JW

    更新日期:2013-05-20 00:00:00

  • Protein tyrosine phosphatase PTP-RR regulates corticosteroid sensitivity.

    abstract:BACKGROUND:We have recently reported that protein phosphate 2A (PP2A) inactivation resulted in increased phosphorylation of the mitogen-activated protein kinase (MAPK) c-Jun N-terminal kinase 1 (JNK1) and glucocorticoid receptors (GR) at Ser(226), thereby reducing GR nuclear translocation and causing corticosteroid ins...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-016-0349-0

    authors: Kobayashi Y,Ito K,Kanda A,Tomoda K,Miller-Larsson A,Barnes PJ,Mercado N

    更新日期:2016-03-24 00:00:00

  • Weighing the evidence for pharmacological treatment interventions in mild COPD; a narrative perspective.

    abstract::There is increasing focus on understanding the nature of chronic obstructive pulmonary disease (COPD) during the earlier stages. Mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1 or the now-withdrawn GOLD stage 0) represents an early stage of COPD that may progress to more severe disease...

    journal_title:Respiratory research

    pub_type: 杂志文章,评审

    doi:10.1186/s12931-019-1108-9

    authors: Singh D,D'Urzo AD,Donohue JF,Kerwin EM

    更新日期:2019-07-08 00:00:00

  • Health care resource utilization and cost for asthma patients regularly treated with oral corticosteroids - a Swedish observational cohort study (PACEHR).

    abstract:BACKGROUND:Patients with severe uncontrolled asthma may receive oral corticosteroid (OCS) treatment regularly. The present study investigated the health care resource utilization and cost in regularly OCS treated Swedish asthma patients. METHODS:Primary care medical records data were linked to data from Swedish nation...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-018-0855-3

    authors: Janson C,Lisspers K,Ställberg B,Johansson G,Telg G,Thuresson M,Nordahl Christensen H,Larsson K

    更新日期:2018-09-03 00:00:00

  • Metformin attenuates lung fibrosis development via NOX4 suppression.

    abstract:BACKGROUND:Accumulation of profibrotic myofibroblasts in fibroblastic foci (FF) is a crucial process for development of fibrosis during idiopathic pulmonary fibrosis (IPF) pathogenesis, and transforming growth factor (TGF)-β plays a key regulatory role in myofibroblast differentiation. Reactive oxygen species (ROS) has...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-016-0420-x

    authors: Sato N,Takasaka N,Yoshida M,Tsubouchi K,Minagawa S,Araya J,Saito N,Fujita Y,Kurita Y,Kobayashi K,Ito S,Hara H,Kadota T,Yanagisawa H,Hashimoto M,Utsumi H,Wakui H,Kojima J,Numata T,Kaneko Y,Odaka M,Morikawa T,Na

    更新日期:2016-08-30 00:00:00

  • Rosiglitazone is a superior bronchodilator compared to chloroquine and β-adrenoceptor agonists in mouse lung slices.

    abstract:BACKGROUND:Current therapy for relieving bronchoconstriction may be ineffective in severe asthma, particularly in the small airways. The aim of this study was to further characterise responses to the recently identified novel bronchodilators rosiglitazone (RGZ) and chloroquine (CQ) under conditions where β-adrenoceptor...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-15-29

    authors: Donovan C,Simoons M,Esposito J,Ni Cheong J,Fitzpatrick M,Bourke JE

    更新日期:2014-03-12 00:00:00

  • High frequency chest wall oscillation for asthma and chronic obstructive pulmonary disease exacerbations: a randomized sham-controlled clinical trial.

    abstract:BACKGROUND:High frequency chest wall oscillation (HFCWO) is used for airway mucus clearance. The objective of this study was to evaluate the use of HFCWO early in the treatment of adults hospitalized for acute asthma or chronic obstructive pulmonary disease (COPD). METHODS:Randomized, multi-center, double-masked phase...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1186/1465-9921-12-120

    authors: Mahajan AK,Diette GB,Hatipoğlu U,Bilderback A,Ridge A,Harris VW,Dalapathi V,Badlani S,Lewis S,Charbeneau JT,Naureckas ET,Krishnan JA

    更新日期:2011-09-10 00:00:00

  • Budesonide/formoterol and formoterol provide similar rapid relief in patients with acute asthma showing refractoriness to salbutamol.

    abstract:BACKGROUND:To compare the efficacy and safety of budesonide/formoterol (Symbicort) with formoterol (Oxis) in the treatment of patients with acute asthma who showed evidence of refractoriness to short-acting beta2-agonist therapy. METHODS:In a 3 hour, randomized, double-blind study, a total of 115 patients with acute a...

    journal_title:Respiratory research

    pub_type: 杂志文章,随机对照试验

    doi:10.1186/1465-9921-7-13

    authors: Bateman ED,Fairall L,Lombardi DM,English R

    更新日期:2006-01-24 00:00:00

  • Macrophage derived chemokine (CCL22), thymus and activation-regulated chemokine (CCL17), and CCR4 in idiopathic pulmonary fibrosis.

    abstract:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a chronically progressive interstitial lung disease of unknown etiology. Previously, we have demonstrated the selective upregulation of the macrophage-derived chemokine CCL22 and the thymus activation-regulated chemokine CCL17 among chemokines, in a rat model of radiati...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-10-80

    authors: Yogo Y,Fujishima S,Inoue T,Saito F,Shiomi T,Yamaguchi K,Ishizaka A

    更新日期:2009-08-29 00:00:00

  • Exposure to common respiratory bacteria alters the airway epithelial response to subsequent viral infection.

    abstract:BACKGROUND:Colonization of the airways with potential pathogenic bacteria is observed in a number of chronic respiratory diseases, such as COPD or cystic fibrosis. Infections with respiratory viruses are known triggers of exacerbations of these diseases. We here investigated if pre-exposure to bacteria alters the respo...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-016-0382-z

    authors: Bellinghausen C,Gulraiz F,Heinzmann AC,Dentener MA,Savelkoul PH,Wouters EF,Rohde GG,Stassen FR

    更新日期:2016-06-03 00:00:00

  • The inhibition of human lung fibroblast proliferation and differentiation by Gs-coupled receptors is not predicted by the magnitude of cAMP response.

    abstract:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease for which there is no cure. Current therapeutics are only able to slow disease progression, therefore there is a need to explore alternative, novel treatment options. There is increasing evidence that the 3', 5' cyclic ade...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-018-0759-2

    authors: Roberts MJ,Broome RE,Kent TC,Charlton SJ,Rosethorne EM

    更新日期:2018-04-07 00:00:00

  • Distinctive lung function trajectories from age 10 to 26 years in men and women and associated early life risk factors - a birth cohort study.

    abstract::Pre-bronchodilator lung function including forced vital capacity (FVC), forced expiratory flow in 1 second (FEV1), their ratio (FEV1/FVC), and forced expiratory flow 25-75% (FEF25-75) measured at age 10, 18, and 26 years in the Isle of Wight birth cohort was analyzed for developmental patterns (trajectories). Early li...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-019-1068-0

    authors: Karmaus W,Mukherjee N,Janjanam VD,Chen S,Zhang H,Roberts G,Kurukulaaratchy RJ,Arshad H

    更新日期:2019-05-22 00:00:00

  • Whole blood RNA sequencing reveals a unique transcriptomic profile in patients with ARDS following hematopoietic stem cell transplantation.

    abstract:BACKGROUND:The acute respiratory distress syndrome (ARDS) is characterized by the acute onset of hypoxemia and bilateral lung infiltrates in response to an inciting event, and is associated with high morbidity and mortality. Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are at increased ...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-019-0981-6

    authors: Englert JA,Cho MH,Lamb AE,Shumyatcher M,Barragan-Bradford D,Basil MC,Higuera A,Isabelle C,Vera MP,Dieffenbach PB,Fredenburgh LE,Kang JB,Bhatt AS,Antin JH,Ho VT,Soiffer RJ,Howrylak JA,Himes BE,Baron RM

    更新日期:2019-01-21 00:00:00

  • DNAH5 is associated with total lung capacity in chronic obstructive pulmonary disease.

    abstract:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is characterized by expiratory flow limitation, causing air trapping and lung hyperinflation. Hyperinflation leads to reduced exercise tolerance and poor quality of life in COPD patients. Total lung capacity (TLC) is an indicator of hyperinflation particularly in ...

    journal_title:Respiratory research

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1186/s12931-014-0097-y

    authors: Lee JH,McDonald ML,Cho MH,Wan ES,Castaldi PJ,Hunninghake GM,Marchetti N,Lynch DA,Crapo JD,Lomas DA,Coxson HO,Bakke PS,Silverman EK,Hersh CP,COPDGene and ECLIPSE Investigators.

    更新日期:2014-08-20 00:00:00

  • The cellular kinetics of lung alveolar epithelial cells and its relationship with lung tissue repair after acute lung injury.

    abstract:BACKGROUND:Organ regeneration in mammals is hypothesized to require a functional pool of stem or progenitor cells, but the role of these cells in lung regeneration is unknown. METHODS:Based on the fact that postnatal regeneration of alveolar tissue has been attributed to alveolar epithelial cells, we established a hem...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-016-0480-y

    authors: Zeng L,Yang XT,Li HS,Li Y,Yang C,Gu W,Zhou YH,Du J,Wang HY,Sun JH,Wen DL,Jiang JX

    更新日期:2016-12-07 00:00:00

  • Critical combination of initial markers for predicting refractory Mycoplasma pneumoniae pneumonia in children: a case control study.

    abstract:BACKGROUND:It is unclear whether the responses of refractory and common Mycoplasma pneumoniae (MP) pneumonia to macrolides differ. Hence, this study aimed to identify biomarkers that may be used to distinguish refractory and common pneumonias caused by MP in children at hospital admission. METHODS:The study included 1...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-019-1152-5

    authors: Choi YJ,Jeon JH,Oh JW

    更新日期:2019-08-23 00:00:00

  • Genes associated with polymorphic variants predicting lung function are differentially expressed during human lung development.

    abstract:BACKGROUND:Recent meta-analyses of genome-wide association studies have identified single nucleotide polymorphisms (SNPs) within/near 54 genes associated with lung function measures. Current understanding of the contribution of these genes to human lung development is limited. We set out to further define i) the expres...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-016-0410-z

    authors: Miller S,Melén E,Merid SK,Hall IP,Sayers I

    更新日期:2016-07-29 00:00:00

  • Factors affecting exhaled nitric oxide measurements: the effect of sex.

    abstract:BACKGROUND:Exhaled nitric oxide (F(E)NO) measurements are used as a surrogate marker for eosinophilic airway inflammation. However, many constitutional and environmental factors affect F(E)NO, making it difficult to devise reference values. Our aim was to evaluate the relative importance of factors affecting F(E)NO in ...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-8-82

    authors: Taylor DR,Mandhane P,Greene JM,Hancox RJ,Filsell S,McLachlan CR,Williamson AJ,Cowan JO,Smith AD,Sears MR

    更新日期:2007-11-15 00:00:00

  • Incidence of asthma and mortality in a cohort of young adults: a 7-year prospective study.

    abstract:BACKGROUND:Few longitudinal data exist on the incidence of asthma in young adults and on the overall mortality risk due to asthma. A 7-year follow-up prospective study was performed to assess the incidence of asthma and mortality from all causes in a cohort of young adults. METHODS:The life status of a cohort of 6031 ...

    journal_title:Respiratory research

    pub_type: 临床试验,杂志文章

    doi:10.1186/1465-9921-6-95

    authors: de Marco R,Locatelli F,Cazzoletti L,Bugianio M,Carosso A,Marinoni A

    更新日期:2005-08-16 00:00:00

  • Heterogeneous burden of lung disease in smokers with borderline airflow obstruction.

    abstract:BACKGROUND:The identification of smoking-related lung disease in current and former smokers with normal FEV1 is complex, leading to debate regarding using a ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) of less than 0.70 versus the predicted lower limit of normal (LLN) for diagnosis of ai...

    journal_title:Respiratory research

    pub_type: 杂志文章,多中心研究

    doi:10.1186/s12931-018-0911-z

    authors: Pirozzi CS,Gu T,Quibrera PM,Carretta EE,Han MK,Murray S,Cooper CB,Tashkin DP,Kleerup EC,Barjaktarevic I,Hoffman EA,Martinez CH,Christenson SA,Hansel NN,Graham Barr R,Bleecker ER,Ortega VE,Martinez FJ,Kanner RE,Paine

    更新日期:2018-11-20 00:00:00

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

    abstract:BACKGROUND:Mechanical 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,...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-018-0822-z

    authors: Wang L,Zhang N,Zhang Y,Xia J,Zhan Q,Wang C

    更新日期:2018-06-22 00:00:00

  • The value of ischemia-modified albumin compared with d-dimer in the diagnosis of pulmonary embolism.

    abstract:STUDY OBJECTIVE:The primary aim of this study was to investigate whether IMA levels are helpful in the diagnosis of pulmonary embolism (PE). The secondary aim was to determine whether IMA was more effective alone or in combination with clinical probability scores in the diagnosis of PE. Thirdly, the sensitivity and spe...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/1465-9921-9-49

    authors: Turedi S,Gunduz A,Mentese A,Topbas M,Karahan SC,Yeniocak S,Turan I,Eroglu O,Ucar U,Karaca Y,Turkmen S,Russell RM

    更新日期:2008-05-30 00:00:00

  • Anti-fibrotic effects of nintedanib in lung fibroblasts derived from patients with idiopathic pulmonary fibrosis.

    abstract:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. The kinase inhibitor nintedanib specific for vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and fibroblast growth factor receptor (FGFR) significantly reduced the rate ...

    journal_title:Respiratory research

    pub_type: 杂志文章

    doi:10.1186/s12931-014-0157-3

    authors: Hostettler KE,Zhong J,Papakonstantinou E,Karakiulakis G,Tamm M,Seidel P,Sun Q,Mandal J,Lardinois D,Lambers C,Roth M

    更新日期:2014-12-12 00:00:00