Researchers at Miguel Hernández University of Elche (UMH) in Spain have found a potential strategy to reduce liver damage and improve vascular function in cirrhosis. The study, published in Biomedicine & Pharmacotherapy, highlights an inflammatory mechanism that could be targeted for new treatments. Cirrhosis is responsible for over one million deaths worldwide each year.
The research was led by Rubén Francés Guarinos from UMH’s Department of Clinical Medicine, with collaboration from the Institute for Health Biotechnology Research, Development and Innovation of Elche (IDiBE UMH), the Hepatic Vascular Biology Group at Hospital Clínic of Barcelona, and the Spanish Biomedical Research Network in Hepatic and Digestive Diseases (CIBERehd).
"Our main objective was to understand the role of platelet-activating factor (PAF) and its receptor (PAF-R) in liver cirrhosis, a disease characterized by progressive liver damage accompanied by intense chronic inflammation," said Francés. He added that the study also assessed whether blocking this pathway could improve liver function.
Cirrhosis is a progressive condition where healthy tissue is replaced by scar tissue, leading to loss of structure and function. It affects more than one million people globally and accounts for about 2.4% of all deaths worldwide. Francés noted: "Beyond mortality, cirrhosis involves a high burden of complications-including infections, bleeding, cognitive impairment, and loss of autonomy-that profoundly affect patients' quality of life."
Current therapies often focus on managing complications rather than addressing underlying biological mechanisms. This underlines the need for research into disease processes that may lead to better interventions.
In their experiments, researchers compared treatments on both healthy and cirrhotic liver tissue. They used BN-52021—a PAF antagonist that blocks PAF-R—and Aza—an inhibitor affecting epigenetic regulation—to see if these could alter disease progression. DNA methylation profiling helped them investigate why PAF-R expression increases abnormally in cirrhosis.
Liver samples from human patients were used alongside mouse models to confirm findings across species. The analysis focused on Kupffer cells—immune cells central to liver inflammation.
The key discovery was that an epigenetic process causes increased PAF-R expression in these cells during cirrhosis. Specifically, demethylation removes a chemical mark on the gene’s promoter region that usually limits its activity; without it, PAF-R becomes overactive and worsens inflammation.
Treatment with BN-52021 reduced structural damage to livers and improved vascular function in mice with cirrhosis. It also helped restore balance within immune responses inside the organ.
The findings suggest future therapies might target epigenetic mechanisms controlling PAF-R as a way to manage inflammation at its source.
