The proteomic response is linked to regional lung volumes in ventilator-induced lung injury

Abstract

It is unclear how acid induced lung injury alters the regional lung volume response to mechanical ventilation (MV) and how this impacts protein expression. Using a mouse model, we investigated the separate and combined effects of acid aspiration and MV on regional lung volumes and how these were associated with the proteome. Adult BALB/c mice were divided into four groups: intratracheal saline, intratracheal acid, Saline/MV or Acid/MV. Specific tidal volume (sVt) and specific end-expiratory volume (sEEV) were measured at baseline and after 2 hours of ventilation using dynamic high-resolution four-dimensional computed tomography (4DCT) images. Lung tissue was dissected into 10 regions corresponding to the image segmentation for label-free quantitative proteomic analysis. Our data showed that acid aspiration significantly reduced sVt and caused further reductions in sVt and sEEV after 2 hours of ventilation. Proteomic analysis revealed 42 dysregulated proteins in both Saline/MV and Acid/MV groups, and 37 differentially expressed proteins in the Acid/MV group. Mapping of the overlapping proteins showed significant enrichment of complement/coagulation cascades (CCC). Analysis of 37 unique proteins in the Acid/MV group identified 6 additional CCC proteins and 7 down-regulated proteins involved in the mitochondrial respiratory chain (MRC). Regional MRC protein levels were positively correlated with sEEV, while the CCC protein levels were negatively associated with sVt. Therefore, this study showed that tidal volume was associated with the expression of CCC proteins while low end-expiratory lung volumes were associated with MRC protein expression, suggesting that tidal stretch and lung collapse activate different injury pathways.

Personalized medicine using omics approaches in acute respiratory distress syndrome to identify biological phenotypes

“…In a rat ARDS model, overexpression of PRDX1 increased the release of IL-6, IL-8, and TNF-α [ 166 ]. Yen et al [ 167 ] showed that, in a rat model, tidal volume was associated with the expression of complement/coagulation cascade proteins, and low end-expiratory lung volumes were associated with expression of mitochondrial respiratory chain protein. They concluded that that tidal stretch and lung collapse can activate different pathways.…”

T-type Calcium Channel Inhibitors Induce Apoptosis in Medulloblastoma Cells Associated With Altered Metabolic Activity

“…Peptide fractions were analysed using 90 min nano ow HPLC gradient and a Top15 DDA-MS method as previously described (9). Individual peptide samples (~1 mg peptide) were analysed by DIA-MS using 26 × 25 amu sequential MS2 scans over the range of 397.5-1027.5 m/z, with 1 amu overlap between windows between MS1 spectra (390 -1240 m/z) acquired at 120k resolution.…”

Protein levels, air pollution and vitamin D deficiency: links with allergy

“…As described previously [ 5 ], asthma and allergic conditions were defined by questionnaire and skin-prick tests respectively, while exposure to annual outdoor NO 2 concentrations was estimated using a validated satellite-based land-use regression model approach [ 6 ]. We measured serum 25-hydroxyvitamin D 3 (25(OH)D 3 ) levels using liquid chromatography–tandem mass spectrometry (LC-MS/MS) and analysed the proteomic profile using Orbitrap LC-MS/MS [ 7 ]. We categorised the participants into low or high NO 2 exposure groups using a threshold of 5.1 ppb based on the mean annual NO 2 exposure of the TAHS cohort (5.1±2.6 ppb, n=1367) [ 5 ] and we defined vitamin D deficiency as a 25(OH)D 3 level <50 nmol·L -1 [ 8 ].…”