# Attenuation of sepsis-induced microvascular permeability and inflammation with the GLP-1R agonist liraglutide.

> **NIH HL F31** · VANDERBILT UNIVERSITY · 2026 · $3,000

## Abstract

Project Abstract
Sepsis is a critical problem around the world causing 20% of all global deaths. The lack of effective
therapeutics leaves critically ill patients with systemic organ dysfunction often caused by damage to the
vascular endothelium. The damage induces micro-vessel dysfunction and increased permeability. Increased
permeability can be attributed to tight junction and adherens junction disruption within endothelial cells. All
blood vessels are lined with a single cell layer of endothelial cells that regulate exchanges between the
bloodstream and the surrounding tissues and modulate inflammation. During sepsis, endothelial cells secrete
circulating inflammatory mediators such as monocyte chemoattractant protein-1 (MCP-1) which cause
upregulation of cell adhesion molecules that facilitate leukocyte trafficking and also MCP-1 also disrupts tight
junctions in endothelial cells. Given the widespread vascular inflammation and breakdown of endothelial tight
junctions in sepsis, therapeutic approaches to maintain and restore endothelial tight junctions is a compelling
treatment strategy. GLP-1R agonists have unexpected anti-inflammatory and permeability attenuation effects.
Preliminary in vitro studies suggest that the protective effects of the GLP-1R agonist, liraglutide, in sepsis are
mediated through microvascular endothelium. Pre-treatment of primary human lung microvascular endothelial
cells with liraglutide improved lipopolysaccharide-induced barrier dysfunction indicating important effects of
liraglutide in protecting the endothelial barrier. In Aim 1, I will define the ability of liraglutide to attenuate
microvascular permeability in vitro and in a clinically relevant murine model of polymicrobial abdominal sepsis.
Additionally, in my preliminary studies, treatment of wild type mice with the GLP-1R agonist liraglutide
significantly decreased plasma MCP-1, attenuated organ injury, and increased survival in a model of
polymicrobial abdominal sepsis. MCP-1 s

## Key facts

- **NIH application ID:** 11389192
- **Project number:** 3F31HL178162-01S1
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** David  Aslaner
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** HL
- **Fiscal year:** 2026
- **Award amount:** $3,000
- **Award type:** 3
- **Project period:** 2025-05-01T00:00:00 → 2028-05-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11389192

## Citation

> US National Institutes of Health, RePORTER application 11389192, Attenuation of sepsis-induced microvascular permeability and inflammation with the GLP-1R agonist liraglutide. (3F31HL178162-01S1). Retrieved via AI Analytics 2026-07-04 from https://api.ai-analytics.org/grant/nih/11389192. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*