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Co-localization of microstructural damage and excessive mechanical strain at aortic branches in angiotensin-II-infused mice

  • Lydia AslanidouEmail author
  • Mauro Ferraro
  • Goran Lovric
  • Matthew R. Bersi
  • Jay D. Humphrey
  • Patrick Segers
  • Bram Trachet
  • Nikos Stergiopulos
Original Paper
  • 125 Downloads

Abstract

Animal models of aortic aneurysm and dissection can enhance our limited understanding of the etiology of these lethal conditions particularly because early-stage longitudinal data are scant in humans. Yet, the pathogenesis of often-studied mouse models and the potential contribution of aortic biomechanics therein remain elusive. In this work, we combined micro-CT and synchrotron-based imaging with computational biomechanics to estimate in vivo aortic strains in the abdominal aorta of angiotensin-II-infused ApoE-deficient mice, which were compared with mouse-specific aortic microstructural damage inferred from histopathology. Targeted histology showed that the 3D distribution of micro-CT contrast agent that had been injected in vivo co-localized with precursor vascular damage in the aortic wall at 3 days of hypertension, with damage predominantly near the ostia of the celiac and superior mesenteric arteries. Computations similarly revealed higher mechanical strain in branching relative to non-branching regions, thus resulting in a positive correlation between high strain and vascular damage in branching segments that included the celiac, superior mesenteric, and right renal arteries. These results suggest a mechanically driven initiation of damage at these locations, which was supported by 3D synchrotron imaging of load-induced ex vivo delaminations of angiotensin-II-infused suprarenal abdominal aortas. That is, the major intramural delamination plane in the ex vivo tested aortas was also near side branches and specifically around the celiac artery. Our findings thus support the hypothesis of an early mechanically mediated formation of microstructural defects at aortic branching sites that subsequently propagate into a macroscopic medial tear, giving rise to aortic dissection in angiotensin-II-infused mice.

Keywords

Angiotensin-II Aortic dissection Biomechanics Aortic strain Synchrotron 

Notes

Acknowledgements

The authors thank the EPFL Histology Facility for staining the histological sections. This work was supported, in part, by the Swiss National Science Foundation (SNF) Grant CR23I2_163370, Research Foundation-Flanders (FWO) fellowship 12A5816N, Research Foundation-Flanders (FWO) project G086917N, and National Institutes of Health (NIH) Grant U01 HL142518. We further acknowledge the Paul Scherrer Institute, Villigen, Switzerland, for provision of synchrotron radiation beamtime at the X02DA TOMCAT beamline of the Swiss Light Source.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Institute of BioengineeringÉcole Polytechnique Fédérale de LausanneLausanneSwitzerland
  2. 2.Centre d’Imagerie BioMédicaleÉcole Polytechnique Fédérale de LausanneLausanneSwitzerland
  3. 3.Swiss Light Source, Paul Scherrer InstituteVilligenSwitzerland
  4. 4.Department of Biomedical EngineeringYale UniversityNew HavenUSA
  5. 5.Department of Biomedical EngineeringVanderbilt UniversityNashvilleUSA
  6. 6.bioMMeda, Ghent UniversityGhentBelgium

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