Molecular Framework of Mouse Endothelial Cell Dysfunction during Inflammation: A Proteomics Approach.

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The therapeutic targeting of ECs has been hampered by concerns regarding organ-specific EC heterogeneity and their response to inflammation. Using in vitro and in silico analysis, we present a comprehensive analysis of the proteomic changes in mouse lung, liver and kidney ECs following exposure to a clinically relevant cocktail of proinflammatory cytokines. Mouse lung, liver and kidney ECs were incubated with TNF-α/IL-1β/IFN-γ for 4 or 24 h to model the cytokine-induced changes. Quantitative label-free global proteomics and bioinformatic analysis performed on the ECs provide a molecular framework for the EC response to inflammatory stimuli over time and organ-specific differences. Gene Ontology and PANTHER analysis suggest why some organs are more susceptible to inflammation early on, and show that, as inflammation progresses, some protein expression patterns become more uniform while additional organ-specific proteins are expressed. These findings provide an in-depth understanding of the molecular changes involved in the EC response to inflammation and can support the development of drugs targeting ECs within different organs. Data are available via ProteomeXchange (identifier PXD031804).", "claims": [{"id": "claim-method", "statement": "The impact of treatment (control vs. cytomix), time (4 h vs. 24 h) and organ (lung, liver, kidney) on the proteomic expression of ECs was investigated using multivariate analysis of variance (MANOVA) for the 19 upregulated proteins and analysis of variance (ANOVA) for the one downregulated protein in JMP Pro (version 16.1).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35955534", "locator": "sections[11] \"4.4. 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