Bronchoalveolar Lavage Fluid Protein Expression in Acute Respiratory Distress Syndrome Provides Insights into Pathways Activated in Subjects with Different Outcomes

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Abstract

Acute respiratory distress syndrome (ARDS) is associated with high mortality. We sought to identify biological pathways in ARDS that differentiate survivors from non-survivors. We studied bronchoalveolar lavage fluid (BALF) from 36 patients with ARDS (20 survivors, 16 non-survivors). Each sample, obtained within seven days of ARDS onset, was depleted of high abundance proteins and labeled for iTRAQ LC-MS/MS separately. Protein identification and relative quantification was performed employing a target-decoy strategy. A variance weighted t-test was used to identify differential expression. Ingenuity Pathway Analysis was used to determine the canonical pathways that differentiated survivors from non-survivors. We identified 1115 high confidence proteins in the BALF out of which 142 were differentially expressed between survivors and non-survivors. These proteins mapped to multiple pathways distinguishing survivors from non-survivors, including several implicated in lung injury and repair such as coagulation/thrombosis, acute phase response signaling and complement activation. We also identified proteins assigned to fibrosis and ones involved in detoxification of lipid peroxide-mediated oxidative stress to be different in survivors and non-survivors. These results support our previous findings demonstrating early differences in the BALF protein expression in ARDS survivors vs. non-survivors, including proteins that counter oxidative stress and canonical pathways associated with fibrosis.

Original languageEnglish (US)
Article number7464
JournalScientific reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Adult Respiratory Distress Syndrome
Bronchoalveolar Lavage Fluid
Survivors
Proteins
Oxidative Stress
Fibrosis
Acute-Phase Reaction
Complement Activation
Lipid Peroxides
Lung Injury
Thrombosis
Mortality

Cite this

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title = "Bronchoalveolar Lavage Fluid Protein Expression in Acute Respiratory Distress Syndrome Provides Insights into Pathways Activated in Subjects with Different Outcomes",
abstract = "Acute respiratory distress syndrome (ARDS) is associated with high mortality. We sought to identify biological pathways in ARDS that differentiate survivors from non-survivors. We studied bronchoalveolar lavage fluid (BALF) from 36 patients with ARDS (20 survivors, 16 non-survivors). Each sample, obtained within seven days of ARDS onset, was depleted of high abundance proteins and labeled for iTRAQ LC-MS/MS separately. Protein identification and relative quantification was performed employing a target-decoy strategy. A variance weighted t-test was used to identify differential expression. Ingenuity Pathway Analysis was used to determine the canonical pathways that differentiated survivors from non-survivors. We identified 1115 high confidence proteins in the BALF out of which 142 were differentially expressed between survivors and non-survivors. These proteins mapped to multiple pathways distinguishing survivors from non-survivors, including several implicated in lung injury and repair such as coagulation/thrombosis, acute phase response signaling and complement activation. We also identified proteins assigned to fibrosis and ones involved in detoxification of lipid peroxide-mediated oxidative stress to be different in survivors and non-survivors. These results support our previous findings demonstrating early differences in the BALF protein expression in ARDS survivors vs. non-survivors, including proteins that counter oxidative stress and canonical pathways associated with fibrosis.",
author = "Maneesh Bhargava and Kevin Viken and Qi Wang and Jagtap, {Pratik D} and Bitterman, {Peter B} and Ingbar, {David H} and Wendt, {Christine H}",
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AU - Bhargava, Maneesh

AU - Viken, Kevin

AU - Wang, Qi

AU - Jagtap, Pratik D

AU - Bitterman, Peter B

AU - Ingbar, David H

AU - Wendt, Christine H

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N2 - Acute respiratory distress syndrome (ARDS) is associated with high mortality. We sought to identify biological pathways in ARDS that differentiate survivors from non-survivors. We studied bronchoalveolar lavage fluid (BALF) from 36 patients with ARDS (20 survivors, 16 non-survivors). Each sample, obtained within seven days of ARDS onset, was depleted of high abundance proteins and labeled for iTRAQ LC-MS/MS separately. Protein identification and relative quantification was performed employing a target-decoy strategy. A variance weighted t-test was used to identify differential expression. Ingenuity Pathway Analysis was used to determine the canonical pathways that differentiated survivors from non-survivors. We identified 1115 high confidence proteins in the BALF out of which 142 were differentially expressed between survivors and non-survivors. These proteins mapped to multiple pathways distinguishing survivors from non-survivors, including several implicated in lung injury and repair such as coagulation/thrombosis, acute phase response signaling and complement activation. We also identified proteins assigned to fibrosis and ones involved in detoxification of lipid peroxide-mediated oxidative stress to be different in survivors and non-survivors. These results support our previous findings demonstrating early differences in the BALF protein expression in ARDS survivors vs. non-survivors, including proteins that counter oxidative stress and canonical pathways associated with fibrosis.

AB - Acute respiratory distress syndrome (ARDS) is associated with high mortality. We sought to identify biological pathways in ARDS that differentiate survivors from non-survivors. We studied bronchoalveolar lavage fluid (BALF) from 36 patients with ARDS (20 survivors, 16 non-survivors). Each sample, obtained within seven days of ARDS onset, was depleted of high abundance proteins and labeled for iTRAQ LC-MS/MS separately. Protein identification and relative quantification was performed employing a target-decoy strategy. A variance weighted t-test was used to identify differential expression. Ingenuity Pathway Analysis was used to determine the canonical pathways that differentiated survivors from non-survivors. We identified 1115 high confidence proteins in the BALF out of which 142 were differentially expressed between survivors and non-survivors. These proteins mapped to multiple pathways distinguishing survivors from non-survivors, including several implicated in lung injury and repair such as coagulation/thrombosis, acute phase response signaling and complement activation. We also identified proteins assigned to fibrosis and ones involved in detoxification of lipid peroxide-mediated oxidative stress to be different in survivors and non-survivors. These results support our previous findings demonstrating early differences in the BALF protein expression in ARDS survivors vs. non-survivors, including proteins that counter oxidative stress and canonical pathways associated with fibrosis.

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