Plasma Constituents Promote Endothelial Thromboinflammatory Dysfunction After Hemorrhagic Shock

Area of Science:

• Trauma and Injury Research
• Vascular Biology
• Immunology

Background:

• Hemorrhagic shock (HS) following trauma involves immune activation and hypercoagulability.
• The role of endothelial cells (ECs) in HS-related thromboinflammation is not fully understood.
• Injury severity's impact on ECs and thrombosis propensity requires further investigation.

Purpose of the Study:

• To investigate the effect of injury severity and HS on endothelial-mediated thromboinflammation.
• To determine if HS plasma increases the risk of thrombosis.
• To elucidate mechanistic links between ECs, thromboinflammation, and post-injury complications.

Main Methods:

• Assessed inflammatory mediators in plasma from trauma patients stratified by HS and injury severity.
• Exposed human lung microvascular endothelial cells (HLMVECs) to patient plasma, measuring thrombin generation and gene expression.
• Induced thrombosis in mice via HS plasma infusion and IVC ligation, followed by histologic analysis.

Main Results:

• Plasma from severe injury and HS patients showed elevated inflammatory mediators.
• HLMVECs exposed to trauma plasma exhibited increased thrombin generation and thromboinflammatory gene expression, especially in HS patients.
• Mice receiving HS plasma developed larger thrombi with increased neutrophil infiltration and reduced EC thrombomodulin.

Conclusions:

• HS plasma enhances endothelial inflammation and coagulation, partly due to inflammatory mediators.
• HS plasma promotes in vivo thrombosis.
• This research clarifies the mechanistic connections between ECs, thromboinflammation, and complications after injury.