Vascular proteome responses precede organ dysfunction in sepsis
Vascular proteome responses precede organ dysfunction in sepsis
Abstract 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.
Sorrentino James T.、Painter Chelsea、Campos Alexandre Rosa、Karlsson Christofer、Morris Claire、Smith Jeffrey W.、Lewis Nathan E.、Golden Gregory J.、Esko Jeffrey D.、Malmstr?m Johan、Nizet Victor、Toledo Alejandro G¨?mez
Bioinformatics and Systems Biology Graduate Program, University of California||Department of Bioengineering, University of CaliforniaDepartment of Cellular and Molecular Medicine, University of California||Glycobiology Research and Training Center, University of CaliforniaThe Cancer Center and The Inflammatory and Infectious Disease Center, Sanford-Burnham-Prebys Medical Discovery InstituteDepartment of Clinical Sciences, Division of Infection Medicine, Lund University, BMCDepartment of Cellular and Molecular Medicine, University of California||Glycobiology Research and Training Center, University of CaliforniaThe Cancer Center and The Inflammatory and Infectious Disease Center, Sanford-Burnham-Prebys Medical Discovery InstituteDepartment of Bioengineering, University of California||Department of Pediatrics, University of California||National Biologics Facility, Technical University of DenmarkDepartment of Cellular and Molecular Medicine, University of California||Glycobiology Research and Training Center, University of CaliforniaDepartment of Cellular and Molecular Medicine, University of California||Glycobiology Research and Training Center, University of CaliforniaDepartment of Clinical Sciences, Division of Infection Medicine, Lund University, BMCDepartment of Pediatrics, University of California||Skaggs School of Pharmacy and Pharmaceutical Sciences, University of CaliforniaDepartment of Clinical Sciences, Division of Infection Medicine, Lund University, BMC
基础医学生物科学研究方法、生物科学研究技术生理学
Vascular glycocalyxproteomesepsisStaphylococcus aureus
Sorrentino James T.,Painter Chelsea,Campos Alexandre Rosa,Karlsson Christofer,Morris Claire,Smith Jeffrey W.,Lewis Nathan E.,Golden Gregory J.,Esko Jeffrey D.,Malmstr?m Johan,Nizet Victor,Toledo Alejandro G¨?mez.Vascular proteome responses precede organ dysfunction in sepsis[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.12.07.471579.点此复制
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