15th Annual Symposium
Physics of Cancer
Leipzig, Germany
Sept. 30 - Oct. 2, 2024
Poster
Rigid restriction: the aortic wall dilemma
Philip Friedrich1, Josephina Haunschild2, Sabrina Friebe3,4, Frank Sauer1, Jörg Schnauß1,5,6,7, Jürgen Lippoldt1, Jannis Korn1, Thomas Fuhs1, Pablo Gottheil1, Kolya Lettl1, Kevin Körner1, Dimitrij Tschodu1, Cary Tutmarc1, Hannah Marie Eichholz1,8,9, Xiaofan Xie1, Paul Mollenkopf1,10, Denny Böttcher11, Stefan G. Mayr3,4, Christian D. Etz2, Josef A. Käs1
1Peter-Debye Institute for Soft Matter Physics, Leipzig University, 04103 Leipzig, Germany
2Department of Cardiac Surgery, Rostock Heart Center, University Medical Center Rostock, 18057 Rostock, Germany
3Leibniz Institute of Surface Engineering (IOM), 04318 Leipzig, Germany
4Division of Surface Physics, Leipzig University, 04103 Leipzig, Germany
5Institute for Didactics of Physics, Leipzig University, 04103 Leipzig, Germany
6Fraunhofer Institute for Cell Therapy and Immunology, DNA Nanodevices, 04103 Leipzig, Germany
7Unconventional Computing Lab, Department of Computer Science and Creative Technologies, University of the West of England, Bristol, BS16 1QY UK
8Leipzig Institute for Meteorology, Leipzig University, 04103 Leipzig, Germany
9Center for Scalable Data Analytics and Artificial Intelligence, Leipzig University, 04105 Leipzig, Germany
10Department of Physiology, University of Pennsylvania, Philadelphia, PA, 19104 USA
11Institute of Veterinary Pathology, Leipzig University, 04103 Leipzig, Germany
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Patients with a bicuspid aortic valve (BAV) are predisposed to a higher risk of developing ascending thoracic aortic aneurysms (ATAAs), which can progress to life-threatening complications such as aortic dissection and rupture. Despite the clinical significance of these outcomes, the underlying biomechanical phenotype responsible for this increased risk remains poorly understood. In our study, we employed a novel multiscale approach in time and length, to conduct a detailed mechanical analysis of tissue samples from patients. We used various techniques, including tensile testing, shear rheology, atomic force microscopy, and tabletop magnetic resonance elastography to assess the mechanical properties of the aortic wall. In addition, we studied the architectural differences in a comprehensive histological analysis.

When comparing BAV ATAA samples to those from patients with a normal tricuspid aortic valve, we observed a distinctive, dense, and highly aligned collagen fiber structure in the tunica media layer of the aorta in BAV patients. This specific fiber organization leads to increased mechanical resistance across all scales, from microscopic to macroscopic levels. Paradoxically, while this structural alignment gives the aortic wall an appearance of mechanical stability, it actually compromises the overall function of the aortic wall, contributing to the development of aortopathy. Our findings suggest that mechanical resistance may serve as a useful predictor for ATAA rupture risk. It questions the diagnostic power of the aortic diameter, which is currently used as the gold standard in clinical diagnosis and highlights the potential of magnetic resonance elastography as a non-invasive tool for clinical risk assessment and monitoring of ATAA progression.
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