The Secretome Deregulations in a Rat Model of Endotoxemic Shock.

V. Cunin,A. Blangy-Letheule,B. Rozec,S. Michelland,J. Dhot,M. Seve,Christian Jung,F. Souab,J. Montnach,S. Bourgoin-Voillard,A. Persello,A. Erraud,V. Aillerie,B. Lauzier,M. De Waard

doi:10.1155/2021/6650464

Abstract

Introduction Septic shock is a systemic inflammatory response syndrome associated with organ failures. Earlier clinical diagnosis would be of benefit to a decrease in the mortality rate. However, there is currently a lack of predictive biomarkers. The secretome is the set of proteins secreted by a cell, tissue, or organism at a given time and under certain conditions. The plasma secretome is easily accessible from biological fluids and represents a good opportunity to discover new biomarkers that can be studied with nontargeted “omic” strategies. Aims To identify relevant deregulated proteins (DEP) in the secretome of a rat endotoxemic shock model. Methods Endotoxemic shock was induced in rats by intravenous injection of lipopolysaccharides (LPS, S. enterica typhi, 0.5 mg/kg) and compared to controls (Ringer Lactate, iv). Under isoflurane anesthesia, carotid cannulation allowed mean arterial blood pressure (MAP) and heart rate (HR) monitoring and blood sampling at different time points (T0 and T50 or T0 and T90, with EDTA and protease inhibitor). Samples were prepared for large-scale tandem mass spectrometry (MS-MS) based on a label-free quantification to allow identification of the proteins deregulated upon endotoxemic conditions. A Gene Ontology (GO) analysis defined several clusters of biological processes (BP) in which the DEP are involved. Results Ninety minutes after shock induction, the LPS group presents a reduction in MAP (-45%, p < 0.05) and increased lactate levels (+27.5%, p < 0.05) compared to the control group. Proteomic analyses revealed 10 and 33 DEP in the LPS group, respectively, at 50 and 90 minutes after LPS injection. At these time points, GO-BP showed alterations in pathways involved in oxidative stress response and coagulation. Conclusion This study proposes an approach to identify relevant DEP in septic shock and brings new insights into the understanding of the secretome adaptations upon sepsis.

Highlights

Septic shock is a systemic inflammatory response syndrome associated with organ failures
We identified deregulated proteins (DEP) of the acute stage of shock that is associated with the deregulation of numerous biological processes such as coagulation or the response to oxidative stress
mean arterial blood pressure (MAP) and heart rate (HR) remained stable in the control group at 90:0 ± 10:0 mmHg and 390:0 ± 10:0 bpm during the whole procedure

Summary

Introduction

Septic shock is a systemic inflammatory response syndrome associated with organ failures. To identify relevant deregulated proteins (DEP) in the secretome of a rat endotoxemic shock model. Endotoxemic shock was induced in rats by intravenous injection of lipopolysaccharides (LPS, S. enterica typhi, 0.5 mg/kg) and compared to controls (Ringer Lactate, iv). Proteomic analyses revealed 10 and 33 DEP in the LPS group, respectively, at 50 and 90 minutes after LPS injection. At these time points, GO-BP showed alterations in pathways involved in oxidative stress response and coagulation. This study proposes an approach to identify relevant DEP in septic shock and brings new insights into the understanding of the secretome adaptations upon sepsis. In 50% of cases, septic shock causes myocardial dysfunction resulting in over 60% excess global mortality [2, 3].

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