Evolving Mural Defects, Dilatation, and Biomechanical Dysfunction in Angiotensin II–Induced Thoracic Aortopathies
2Department of Surgery, Yale University, USA
3Vascular Biology and Therapeutics Program, Yale School of Medicine, USA
4Biomecanics, Mines Saint-Etienne, University of Lyon, University Jean Monnet, France
5Department of Mechanical Engineering and Materials Science, Washington University in St. Louis, Washington University in St. Louis, USA
Objective – To quantify the natural history of thoracic aortopathy in a common mouse model and to identify robust correlations between aortic dilatation and localized mural defects. Approach and Results – We combined a high-resolution multi-modality imaging approach (panoramic digital image correlation and optical coherence tomography) with biaxial mechanical testing to correlate local changes in aortic wall defects and mechanics for the first time. Results revealed strong correlations between local decreases in elastic energy storage and increases in circumferential material stiffness and increasing proximal aortic diameter and especially mural defect size. Conclusions – While aneurysmal dilatation is often observed within particular segments of the aorta, dissection and rupture initiate as highly localized mechanical failures. We show that wall composition and material properties are compromised in dilated regions, but especially so in regions of intramural delaminations and partial medial ruptures, both of which further increase the vulnerability of the wall. Therapies that promote robust collagen accumulation promise to protect the wall from these vulnerabilities, which increase the risk of dissection and rupture.