PhD Scientific Days 2022

Translational Medicine III.

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

Előadó neve

Dr. Stengl, Roland

Előadó munkahelye

Heart and Vascular Center, Semmelweis University; Center for Cardiovascular Genetics and Gene Diagnostics, Foundation for People with Rare Diseases, Schlieren-Zurich, Switzerland

Előadó telefonszáma

06703949950

Előadó e-mail címe

rolandstengl01@gmail.com

Az előadás címe

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

Szerző(k) neve és munkahelye

Roland Stengl1,2, Nicolo Dubacher1, Marc T. Schönholzer1, Szilamér Ferenczi3, Janine Meienberg1, Kálmán Benke2, Zoltán Szabolcs2, Gabor Matyas1,4

1Center for Cardiovascular Genetics and Gene Diagnostics, Foundation for People with Rare Diseases, Schlieren-Zurich, Switzerland;
2Heart and Vascular Center, Semmelweis University, Budapest, Hungary;
3Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, Budapest, Hungary;
4Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland

Bemutatás módja

Szóbeli

Szekció

Translational Medicine III.

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

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

University and Doctoral School

Semmelweis University, Doctoral School of Theoretical and Translational Medicine

Supervisor

Dr Benke Kálmán, Prof Dr Szabolcs Zoltán

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6926

Start

15:30

End

15:45

Authors (legacy)

Roland Stengl1,2, Nicolo Dubacher1, Marc T. Schönholzer1, Szilamér Ferenczi3, Janine Meienberg1, Kálmán Benke2, Zoltán Szabolcs2, Gabor Matyas1,4

1Center for Cardiovascular Genetics and Gene Diagnostics, Foundation for People with Rare Diseases, Schlieren-Zurich, Switzerland;
2Heart and Vascular Center, Semmelweis University, Budapest, Hungary;
3Laboratory of Molecular Neuroendocrinology, Institute of Experimental Medicine, Budapest, Hungary;
4Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland