# Distinct patterns of endothelial response to endotoxin in aged mice as compared to young mice

## TL;DR

Aging changes how blood vessel linings respond to endotoxin, leading to more severe organ damage and different injury patterns in older mice.

## Contribution

The study reveals age-specific endothelial response patterns to endotoxin, highlighting glycocalyx injury and hemostasis differences.

## Key findings

- Aged mice showed more severe systemic inflammation and organ injury after LPS exposure.
- Endothelial glycocalyx injury and permeability biomarkers were uniquely elevated in aged mice.
- Inflammation and classical hemostasis markers responded similarly in young and aged mice.

## Abstract

Aging exacerbates organ injury in endotoxemia, but it is not clear whether endotoxemia is associated with a specific, age-related profile of the endothelial response. Therefore, the aim of the study was to assess the pattern of endothelial response to lipopolysaccharide (LPS) in aged mice (18-month-old) as compared to young mice (3-month-old). Our analysis was based on functional endothelial responses measured in vivo by magnetic resonance imaging (MRI) and on a comprehensive panel of biomarkers of endothelial dysfunction measured by micro-flow liquid chromatography tandem mass spectrometry (microLC-MS/MS). In aged mice, the systemic inflammatory response (serum amyloid A, IL-1β, IL-2, eotaxin), kidney injury (urea), liver injury (ALT), and endothelial dysfunction induced by a relatively low dose of LPS (3 mg/kg) were all more pronounced as compared with young mice. Interestingly, in aged mice, LPS induced a different pattern of endothelial response compared to young mice, as evidenced by glycocalyx injury biomarkers (SDC-1, ESM-1), the endothelial permeability biomarkers (Angpt-2, sTie-2) and various hemostasis-related factors (sTM, TAFI, THBS-1). In contrast, biomarkers of endothelial inflammation (sVCAM-1, sICAM-1, sE-selectin, sP-selectin) and classical hemostasis biomarkers (PAI-1, t-PA, von Willebrand factor) displayed comparable responses to LPS in aged and young mice. In conclusion, aging does not indiscriminately potentiate LPS-induced inflammatory mediator generation in the current model of endotoxemia induced by a relatively low dose of LPS, but selectively alters the endothelial response in terms of glycocalyx injury, endothelial permeability, and hemostasis.

The online version contains supplementary material available at 10.1007/s11357-025-01838-9.