The pan-PPAR agonist lanifibranor reduces portal pressure independent of fibrosis reduction through the splanchnic vasculature
In this study by Heldens et al., the X-CUBE was used to evaluate the volume of mesenteric large-sized veins by analyzing mesenteric vascular corrosion casts. The X-CUBE provided 3D visualization and quantification of such vessels, gaining structural information and allowing the researchers to quantify the veins volume in treated and untreated groups.
Research question
Portal hypertension (PH) is a serious complication of advanced chronic liver disease, which can arise from structural and functional changes of the vasculature and an increase in portal pressure. Lanifibranor has shown potential in reducing portal pressure and fibrosis in preclinical models but the direct effect on PH remains unclear. This study investigates lanifibranor’s effect on PH independent of fibrosis by analyzing vascular changes in fibrotic as well as non-fibrotic mouse models.
Experiment
The X-CUBE was used in this study to acquire high-resolution µCT scans of mice vasculature. For this experiment, a vascular corrosion casting protocol was followed to preserve the original structure of terminally anaesthetised mice’s vessels. The X-CUBE was used at 50 kV tube voltage and a 225 µA tube current, which allowed for high-quality images of the vascular structures. The acquired data was reconstructed to 3D images with 50 µm voxel size to visualize and analyze the vascular structures. Volumes of Interest (VOIs) were drawn automatically by using HU-based segmentation (-700–100 HU) to delineate the vessels, which made it possible to segment and calculate the vessel’s volume.
Results
The study found that lanifibranor reduced the number of small splanchnic blood vessels due to its antiangiogenic effects. However, when examining the large mesenteric veins using µCT, no change in their volume was observed after one week of treatment. This suggests that lanifibranor specifically targeted smaller vessels, leaving the larger mesenteric veins unaffected.
The figure below shows how lanifibranor affects angiogenesis in a mouse model of isolated PH. Part A displays detailed images of mesenteric tissue using scanning electron microscopy (SEM) and µCT, which provide a close-up look at the structure of the blood vessels. Part B shows the relative volume of large mesenteric veins based on µCT, indicating whether lanifibranor treatment affected the volume of these larger blood vessels.
Figure adapted from Heldens et al. Biomedicine & Pharmacotherapy 183 (2025) 117826
The X-CUBE provided high-resolution µCT scans that allowed researchers to visualize and analyze the 3D structure and volume of mesenteric veins in great detail. This enabled them to assess the effects of lanifibranor on these veins, specifically focusing on large vessels.
