# The role of pathologic plasmin activity in trauma-induced systemic inflammatory response syndrome

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2020 · $30,221

## Abstract

Project Summary: Severe injury is a leading cause of death and disability worldwide, largely
attributed to fatal complications that arise from the injury. While an isolated injury heals over time
without notable consequence, a severe injury provokes systemic inflammatory response syndrome
(SIRS) and coagulation dysfunction, which greatly increase the risk of life-threatening complications
such as bleeding, multiple organ dysfunction syndrome, and thrombosis. The complex molecular
changes that drive the development of these complications are obscure. Consequently, while medical
advances (such as blood transfusions) have allowed trauma patients to survive their injuries, few
therapeutics exist to effectively prevent fatal complications and promote recovery in these patients.
 Plasmin, the serine protease responsible for fibrin degradation (fibrinolysis), is critical for tissue
repair later in convalescence following an injury, however, a severe injury pathologically alters the
timing and magnitude of its activity. Severe injuries provoke early, excess plasmin activation, leading
to inappropriate fibrin degradation (hyperfibrinolysis), bleeding, and increased risk of death. Recent
studies on the use of antifibrinolytic drugs in trauma and surgical patients have demonstrated that
early inhibition of this inappropriate plasmin activation not only reduces bleeding but also reduces
inflammation and associated complications. While its canonical role of fibrinolysis makes it a critical
regulator of coagulation, plasmin's physiologic roles extend to modulation of inflammatory signaling
and cell migration. Therefore, we hypothesized that excess plasmin activity is a key molecular driver
of trauma-induced SIRS, predisposing patients to acute and chronic inflammatory complications.
 The purpose of this proposal is to investigate mechanisms of excess plasmin activation and its
role in SIRS following severe injury. A model of thermal injury will be used in which excess plasmin
activation occurs without risk of bleeding. While plasmin is a key target in the reduction of bleeding in
trauma patients, therapeutics currently used in the clinic to prevent bleeding and novel pharmacologic
modulators of this system may also be used to reduce or prevent inflammation-associated
complications, if dosed appropriately. Within the proposed studies, I will implement genetic and
pharmacologic tools to manipulate plasmin activity in an animal model of thermal injury, which reliably
provokes SIRS, in order to quantify the effect of plasmin activity on inflammation. In addition to
serologic measures of cytokines, I will use NF- κB-luciferase reporter mice to track systemic changes
in both acute and chronic inflammation at the organ and cellular level over time following the thermal
injury. The goal of this work is to identify both therapeutic targets and predictive diagnostic tools that
may be used to reduce inflammatory complications and improve outcomes in trauma patients.

## Key facts

- **NIH application ID:** 10059140
- **Project number:** 5F31HL149340-02
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Breanne Helen Yvonne Gibson
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $30,221
- **Award type:** 5
- **Project period:** 2019-09-30 → 2021-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10059140

## Citation

> US National Institutes of Health, RePORTER application 10059140, The role of pathologic plasmin activity in trauma-induced systemic inflammatory response syndrome (5F31HL149340-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10059140. Licensed CC0.

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