Belgian Heart Fund: "Exploring the cell-specific mechanisms of aortic disease using fibrillin-1 mutant mouse models"

01 January 2023 → 31 December 2024
Funding by bilateral agreement (private and foundations)
Research disciplines
  • Natural sciences
    • Transcriptomics
  • Medical and health sciences
    • Vascular diseases
  • Engineering and technology
    • Genetically modified animals
Aortic disease mouse model Single cell transcriptomics Marfan Syndrome
Project description

Marfan syndrome is a rare hereditary disorder caused by defects in the fibrillin-1 gene. Patients with Marfan syndrome have a significantly increased risk of developing tissue damage in the aorta, the largest artery in the body that carries the oxygenated blood pumped from the heart. The damage to the aortic wall can cause this blood vessel to rupture, which is an acute life-threatening situation. In our research we aim to understand the underlying mechanisms that lead from a defect in the fibrillin-1 gene to the development of tissue damage in the aortic wall. In our research program we use genetically engineered mice, which have specific defects in the fibrillin-1 gene. In our recent study, we were able to show that in one of these models a mild, highly localized form of aortic damage was present, while in another model the damage was much more extensive and even spontaneous rupture of the aorta could occur, resulting in death. In this project we want to compare these two models, using a sensitive technique that allows us to determine for each cell in an aortic sample how strongly each gene is activated throughout the genome. This will give us very valuable information about the specific types of cells associated with different stages of aortic damage, and which molecular signaling pathways are activated in these cells. Based on these data, we expect that we will be able to better understand the disease processes, which will contribute to better treatment of patients suffering from aortic diseases in the future.