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Transcriptome Analysis Revealed Inflammation Is Involved in the Impairment of Human Umbilical Vein Endothelial Cells Induced by Post-hemorrhagic Shock Mesenteric Lymph.

ABSTRACT: Vascular endothelial injury caused by post-hemorrhagic shock mesenteric lymph (PHSML) return is an important manifestation during refractory hemorrhagic shock. Using human umbilical vein endothelial cells (HUVECs) and transcriptome analysis, this study sought to investigate the molecular mechanism underlying the adverse effect of PHSML on vascular endothelium. Post-hemorrhagic shock mesenteric lymph was collected from male rats after they underwent hemorrhagic shock and following resuscitation, while normal mesenteric lymph (NML) was harvested from sham rats. Human umbilical vein endothelial cells were incubated with the culture medium containing either 10% phosphate buffered saline (Control), NML, or PHSML for 3 h, and then were harvested for RNA sequencing. In comparison with NML treated cells, 37 genes were differentially expressed in PHSML-treated HUVECs, including 32 upregulated genes and five downregulated genes. These differentially expressed genes were mainly enriched in inflammatory pathways, including signaling pathways for activation of the NOD-like receptors, NF-?B, and TNF. Furthermore, we found that C-C motif chemokine ligand 2 (CCL2) was increased significantly after PHSML treatment, and Bindarit, a CCL2 production inhibitor, attenuated the damage of HUVECs induced by PHSML. The results provide molecular evidence on vascular endothelium damage caused by PHSML. C-C motif chemokine ligand 2 might represent a new target for reducing vascular injury after severe hemorrhagic shock.

SUBMITTER: Wang Q

PROVIDER: S-EPMC7509150 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Transcriptome Analysis Revealed Inflammation Is Involved in the Impairment of Human Umbilical Vein Endothelial Cells Induced by Post-hemorrhagic Shock Mesenteric Lymph.

Wang Qi Q Chi Zhen-Fen ZF Wei Di D Zhao Zhen-Ao ZA Zhang Hong H Zhang Li-Min LM Liu Yan-Xu YX Kang An-Ling AL Zhao Meng M Wang Peng P Nie Ling-Hu LH Niu Chun-Yu CY Zhao Zi-Gang ZG

Frontiers in immunology 20200909

Vascular endothelial injury caused by post-hemorrhagic shock mesenteric lymph (PHSML) return is an important manifestation during refractory hemorrhagic shock. Using human umbilical vein endothelial cells (HUVECs) and transcriptome analysis, this study sought to investigate the molecular mechanism underlying the adverse effect of PHSML on vascular endothelium. Post-hemorrhagic shock mesenteric lymph was collected from male rats after they underwent hemorrhagic shock and following resuscitation, ...[more]

PMID: 33013823

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Project description:BackgroundTrauma/hemorrhagic shock (T/HS) causes a release of proinflammatory mediators into the mesenteric lymph (ML) that may trigger a systemic inflammatory response and subsequent organ failure. Recently, we showed that exosomes in postshock ML are biologically active mediators of this inflammation. Because the specific inflammatory mediators in postshock ML exosomes have yet to be characterized, we hypothesized that T/HS would lead to a distinct ML proinflammatory exosome phenotype that could be identified by proteomic analysis. We further hypothesized that their regulation by the neuroenteric axis via the vagus nerve would modify this proinflammatory profile.MethodsMale rats underwent an established T/HS model including 60 minutes of HS followed by resuscitation. Mesenteric lymph was collected before HS (preshock) and after resuscitation (postshock). A subset of animals underwent cervical vagus nerve electrical stimulation (VNS) after the HS phase. Liquid chromatography with tandem mass spectroscopy (LC-MS/MS) followed by protein identification, label free quantification, and bioinformatic analysis was performed on exosomes from the pre-shock and post-shock phases in the T/HS and T/HS + vagus nerve electrical stimulation groups. Biological activity of exosomes was evaluated using a monocyte nuclear factor kappa B (NF-κB) activity assay.ResultsML exosomes express a distinct protein profile after T/HS with enrichment in pathways associated with cell signaling, cell death and survival, and the inflammatory response. Stimulation of the vagus nerve following injury attenuated the transition of ML exosomes to this T/HS-induced inflammatory phenotype with protein expression remaining similar to pre-shock. Monocyte NF-κB activity was increased after exposure to ML exosomes harvested after T/HS, while ML exosomes from preshock had no effect on monocyte NF-κB expression.ConclusionPostshock ML exosomes carry a distinct, proinflammatory protein cargo. Stimulating the vagus nerve prevents the T/HS-induced changes in ML exosome protein payload and suggests a novel mechanism by which the neuroenteric axis may limit the systemic inflammatory response after injury.

Dataset Information

Transcriptome Analysis Revealed Inflammation Is Involved in the Impairment of Human Umbilical Vein Endothelial Cells Induced by Post-hemorrhagic Shock Mesenteric Lymph.

Publications

Transcriptome Analysis Revealed Inflammation Is Involved in the Impairment of Human Umbilical Vein Endothelial Cells Induced by Post-hemorrhagic Shock Mesenteric Lymph.

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