A New Approach to Visualize and Characterize the Lymphatic Vasculature in Atherosclerosis
Carolin Christ
Molecular Medicine Division
Dr. Várnai Péter
SE, Elméleti Orvostudományi Központ, Háry Pál terem
2025-09-05 15:00:00
Cellular and Molecular Physiology
Dr. Hunyady László
Dr. Jakus Zoltán
Dr. Török Marianna
Dr. Engelmann Péter
Dr. Koller Ákos
Dr. Tamási Viola
Dr. Kövesdi Dorottya
Organ-specific lymphatics play a crucial role in maintaining tissue homeostasis and influencing the development of various diseases. However, understanding their precise functions has been challenging due to limitations in visualization techniques. This study presents a novel approach to overcoming these challenges, providing new insights into lymphatic function across different organs with a focus on the great vessels.
The objectives of this study were to develop and validate a visualization technique to achieve efficient and detailed visualization of lymphatic structures across various mouse organs. Additionally, we aimed to investigate the role of lymphatic vessels in atherosclerosis, with a focus on sex-specific differences.
We employed a modified CUBIC tissue-clearing protocol coupled with whole-mount immunostaining to visualize lymphatic structures in mouse organs. This method was applied to Flt4kd/+ mice, a model for lymphedema, as well as to ApoE-/- and LDLR-/- mice, mouse models for atherosclerosis. Quantification of lymphatic networks was performed using AngioTool, a software tool for the assessment of vascular structures.
Our method successfully enabled high-quality imaging of lymphatic structures across various mouse organs without the need for specialized equipment, offering a cost-effective alternative for researchers. Application of the technique to Flt4kd/+ mice revealed significant morphological alterations in lymphatic structures across multiple organs. In the context of atherosclerosis, we found that lymphatic vessels were unevenly distributed within the arterial tree, with sparse presence in the aortic arch and abundance in the abdominal and femoral arteries. Additionally, female mice on Western diet developed larger plaques with more significant calcifications than male mice and enhanced peripheral lymphatic function, suggesting sex-specific factors in plaque formation and lymphatic function during atherosclerosis.
Our findings underscore the critical role of organ-specific lymphatics in both health and disease. The novel tissue-clearing and visualization technique developed in this study provides a powerful tool for researchers to explore lymphatic function and its involvement in disease pathogenesis. The observed sex-specific differences in plaque formation and lymphatic function in atherosclerosis highlight the need for further research into lymphatic involvement in disease and the potential for therapeutic interventions targeting these pathways.
