PhD Scientific Days 2022

Translational Medicine III.

Novel assay to assess the aortic rupture of mice modeling aortic diseases

Text of the abstract

Introduction: Thoracic aortic aneurysms and dissections (TAAD) characterized by a weakened aortic wall are a common cause of premature death. TAAD can be divided into syndromic and non-syndromic forms. An example for a syndromic TAAD is vascular Ehlers-Danlos syndrome (vEDS), which is a rare systemic connective tissue disorder, caused by mutations in the COL3A1 gene, leading to weakened connective tissue, including the aorta.

Aims: Previously, we have established an objective read-out system to measure the tensile force by stretching short murine thoracic aortic segments until rupture, with the aim of evaluating the effect of various medications on the biomechanical integrity of the aorta. Here, to gain deeper insight into the biomechanical integrity of the aorta, we present an additional, more physiological read-out system of the aortic rupture force.

Methods: Our novel assay assesses the burst pressure of the murine aorta by creating a fluid-induced load/stress on the aortic wall, thereby enabling the identification of the weakest (rupturing) site in the aortic wall by investigating the entire thoracic aorta. For this, we create a closed in situ system in euthanized mice and increase the intraluminal pressure with liquid until aortic rupture. The burst pressure at which the aortic rupture occurs is recorded (in mmHg).

Results: The application of our novel assay to wild-type and untreated heterozygous mice modeling vEDS (Col3a1+/m1Lsmi) showed that wild-type mice had significantly higher burst pressure than heterozygous mice. The comparison with our previously established method for measuring aortic rupture force will be presented.

Conclusion: Our novel assay of burst pressure measurement can be used as an objective read-out system for assessing the biomechanical integrity of the entire thoracic aorta, enabling the evaluation of drugs to strengthen the weakened aortic wall in mice modeling aortic diseases.

Funding

New National Excellence Program of the Ministry for Innovation and Technology, ÚNKP-21-3-I-SE-75

Developing Scientific Workshops of Medical-, Health Sciences and Pharmaceutical Training (grant number: EFOP-3.6.3-VEKOP-16-2017-00009