Cystic fibrosis (CF) is a frequent genetic disorder, with a median survival rising to more than 35 years. CF is
invalidating for patients and greatly affects the quality of life. Lung disease is the most serious aspect.
However, CF liver disease (CFLD) is also frequent, affecting 1/3 of the patients and can lead to liver
transplantation or dead.
It is still unclear how this liver disease develops. The classical ‘biliary’ hypothesis does not fit with all of the
findings in CFLD. Recently, we have demonstrated abnormalities in the small blood vessels of the liver (portal
vein branches) that can explain the disease mechanism of CFLD.
Now, we will focus on the endothelial cells (ECs) that line the inside of these blood vessels. We will study in
detail the characteristics of these ECs by using four sources of ECs: i) genetically altered CF‐like EC‐lines; ii) ECs
isolated from the liver of a mouse model of CF; iii) ECs isolated from CF patient explant organs and iv)
circulating ECs present in the blood of CF patients with and without liver disease. These ECs will be extensively
studied (endothelial function, metabolism and their genetic signature).
This is the first in depth analysis of the ECs in CF and CFLD and will give better insight in the development of
CFLD. This could provide new targets for treatment as there is currently no preventive or therapeutic option.