期刊
JOURNAL OF PROTEOME RESEARCH
卷 13, 期 2, 页码 640-649出版社
AMER CHEMICAL SOC
DOI: 10.1021/pr4007624
关键词
biomarkers; critical illness; metabolomics; lung injury; bioinformatics; phospholipids; lactate; xanthine oxidase; hippurate; pharmacotherapy
资金
- Michigan Nutrition Obesity Research Center
- Michigan Regional Comprehensive Metabolomics Research Core
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [P30 DK089503, DK097153]
- National Heart, Lung and Blood Institute (NHLBI) [P50 HL074924]
- University of Michigan Center for Computational Medicine and Bioinformatics Pilot Project Grant
- [K25 DK092558]
Acute respiratory distress syndrome (ARDS) remains a significant hazard to human health and is clinically challenging because there are no prognostic biomarkers and no effective pharmacotherapy. The lung compartment metabolome may detail the status of the local environment that could be useful in ARDS biomarker discovery and the identification of drug target opportunities. However, neither the utility of bronchoalveolar lavage fluid (BALF) as a biofluid for metabolomics nor the optimal analytical platform for metabolite identification is established. To address this, we undertook a study to compare metabolites in BALF samples from patients with ARDS and healthy controls using a newly developed liquid chromatography (LC)-mass spectroscopy (MS) platform for untargeted metabolomics. Following initial testing of three different high-performance liquid chromatography (HPLC) columns, we determined that reversed phase (RP)-LC and hydrophilic interaction chromatography (HILIC) were the most informative chromatographic methods because they yielded the most and highest quality data. Following confirmation of metabolite identification, statistical analysis resulted in 37 differentiating metabolites in the BALF of ARDS compared with health across both analytical platforms. Pathway analysis revealed networks associated with amino acid metabolism, glycolysis and gluconeogenesis, fatty acid biosynthesis, phospholipids, and purine metabolism in the ARDS BALF. The complementary analytical platforms of RPLC and HILIC-LC generated informative, insightful metabolomics data of the ARDS lung environment.
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