Vascular proteome responses precede organ dysfunction in sepsis Article Swipe

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James T. Sorrentino , Gregory J. Golden , Claire Morris , Chelsea D. Painter , Victor Nizet , Alexandre Rosa Campos , Jeffrey W. Smith , Christofer Karlsson , Johan Malmström , Nathan E. Lewis , Jeffrey D. Esko , Alejandro Gómez Toledo ·

YOU? · · 2021 · Open Access · · DOI: https://doi.org/10.1101/2021.12.07.471579

Vascular dysfunction and organ failure are two distinct, albeit highly interconnected clinical outcomes linked to morbidity and mortality in human sepsis. The mechanisms driving vascular and parenchymal damage are dynamic and display significant molecular crosstalk between organs and tissues. Therefore, assessing their individual contribution to disease progression is technically challenging. Here, we hypothesize that dysregulated vascular responses predispose the organism to organ failure. To address this hypothesis, we have evaluated four major organs in a murine model of S. aureus sepsis by combining in vivo labeling of the endothelial proteome, data-independent acquisition (DIA) mass spectrometry, and an integrative computational pipeline. The data reveal, with unprecedented depth and throughput, that a septic insult evokes organ-specific proteome responses that are highly compartmentalized, synchronously coordinated, and significantly correlated with the progression of the disease. Vascular proteome changes were found to precede bacterial invasion and leukocyte infiltration into the organs, as well as to precede changes in various well-established cellular and biochemical correlates of systemic coagulopathy and tissue dysfunction. Importantly, our data suggests a potential role for the vascular proteome as a determinant of the susceptibility of the organs to undergo failure during sepsis.

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Sepsis Proteome Biology Organ dysfunction Crosstalk Coagulopathy Disease Septic shock Immunology Medicine Pathology Bioinformatics Internal medicine Physics Optics

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1101/2021.12.07.471579
PDF: https://www.biorxiv.org/content/biorxiv/early/2021/12/09/2021.12.07.471579.full.pdf
OA Status: green
References: 33
Related Works: 10
OpenAlex ID: https://openalex.org/W4200154402

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DOI: https://doi.org/10.1101/2021.12.07.471579

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Title: Vascular proteome responses precede organ dysfunction in sepsis

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Type: preprint

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Language: en

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Publication year: 2021

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Publication date: 2021-12-09

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Authors: James T. Sorrentino, Gregory J. Golden, Claire Morris, Chelsea D. Painter, Victor Nizet, Alexandre Rosa Campos, Jeffrey W. Smith, Christofer Karlsson, Johan Malmström, Nathan E. Lewis, Jeffrey D. Esko, Alejandro Gómez Toledo

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Landing page: https://doi.org/10.1101/2021.12.07.471579

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PDF URL: https://www.biorxiv.org/content/biorxiv/early/2021/12/09/2021.12.07.471579.full.pdf

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OA URL: https://www.biorxiv.org/content/biorxiv/early/2021/12/09/2021.12.07.471579.full.pdf

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Concepts: Sepsis, Proteome, Biology, Organ dysfunction, Crosstalk, Coagulopathy, Disease, Septic shock, Immunology, Medicine, Pathology, Bioinformatics, Internal medicine, Physics, Optics

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