# Oxidized LDL dependent reprogramming of the liver lymphatic endothelium

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $421,077

## Abstract

Project Summary
The lymph in the liver originates predominantly from the blood vascular system, which is characterized by a
portal vein and hepatic artery in the portal triad spanning the hepatic lobule to the central vein. Fluid from the
blood vasculature leaks into the interstitium of the liver through fenestrae in liver sinusoids. These fenestrae
result in a higher protein content of hepatic lymph as compared to lymph in other organs. The high protein
content normally found in the liver draining lymph is lower during chronic liver disease. We observe similar
changes in lymph content in mice with diet-induced liver disease. If this alteration in lymph protein content is
due to defective liver lymphatic function is unknown. Intriguingly, when we treat mice with chronic liver disease
with a lymphatic growth factor we are able to rescue lymphatic drainage and decrease inflammation in the liver.
These novel findings demonstrate that the lymphatic endothelium in the liver important for maintaining liver
homeostasis. We also find that highly oxidized low-density lipoprotein (oxLDL) injection has a similar effect on
lymphatic removal of protein as a mouse model of chronic liver disease. We discovered that oxLDL induced
significant changes in the transcriptional and metabolic profile of LECs which indicate a functional change in
LECs. Furthermore, we found that these oxLDL-induced changes were dependent on the oxLDL receptor
CD36 both in vitro and in vivo, suggesting a potential mechanism by which oxLDL induces liver lymphatic
dysfunction. In this proposal will use both in vitro and in vivo models to establish the molecular and cellular
consequences of oxLDL signaling in LECs that cause decreased liver lymphatic function. These studies will be
the first to directly address how lymphatics in the liver react to an inflammatory mediator associated with liver
disease, oxLDL, and potentially identify novel therapeutic targets to modulate lymphatic function in the setting
of chronic liver disease.

## Key facts

- **NIH application ID:** 10176480
- **Project number:** 5R01DK125595-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Matthew A Burchill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $421,077
- **Award type:** 5
- **Project period:** 2020-06-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10176480

## Citation

> US National Institutes of Health, RePORTER application 10176480, Oxidized LDL dependent reprogramming of the liver lymphatic endothelium (5R01DK125595-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10176480. Licensed CC0.

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