title: The effects of angiotensin II on the coupled microstructural and biomechanical response of C57BL/6 mouse aorta.
abstract: BACKGROUND
  Abdominal aortic aneurysm (AAA) is a complex disease that leads to a localized dilation of the infrarenal aorta, the rupture of which is associated with significant morbidity and mortality. Animal models of AAA can be used to study how changes in the microstructural and biomechanical behavior of aortic tissues develop as disease progresses in these animals. We chose here to investigate the effect of angiotensin II (AngII) in C57BL/6 mice as a first step towards understanding how such changes occur in the established ApoE(-/-) AngII infused mouse model of AAA.
  
  
  OBJECTIVE
  The objective of this study was to utilize a recently developed device in our laboratory to determine how the microstructural and biomechanical properties of AngII-infused C57BL/6 wildtype mouse aorta change following 14 days of AngII infusion.
  
  
  METHODS
  C57BL/6 wildtype mice were infused with either saline or AngII for 14 day. Aortas were excised and tested using a device capable of simultaneously characterizing the biaxial mechanical response and load-dependent (unfixed, unfrozen) extracellular matrix organization of mouse aorta (using multiphoton microscopy). Peak strains and stiffness values were compared across experimental groups, and both datasets were fit to a Fung-type constitutive model. The mean mode and full width at half maximum (FWHM) of fiber histograms from two photon microscopy were quantified in order to assess the preferred fiber distribution and degree of fiber splay, respectively.
  
  
  RESULTS
  The axial stiffness of all mouse aorta was found to be an order of magnitude larger than the circumferential stiffness. The aortic diameter was found to be significantly increased for the AngII infused mice as compared to saline infused control (p=0.026). Aneurysm, defined as a percent increase in maximum diameter of 30% (defined with respect to saline control), was found in 3 of the 6 AngII infused mice. These three mice displayed adventitial collagen that lacked characteristic fiber crimp. The biomechanical response in the AngII infused mice showed significantly reduced circumferential compliance. We also noticed that the ability of the adventitial collagen fibers in AngII infused mice to disperse in reaction to circumferential loading was suppressed.
  
  
  CONCLUSIONS
  Collagen remodeling is present following 14 days of AngII infusion in C57BL/6 mice. Aneurysmal development occurred in 50% of our AngII infused mice, and these dilatations were accompanied with adventitial collagen remodeling and decreased circumferential compliance.
authors.affiliation: Graduate Interdisciplinary Program of Biomedical Engineering, The University of Arizona, Tucson, AZ 85721-0119, USA.
authors.forename: Darren
authors.initials: D
authors.lastname: Haskett
authors.forename: Erin
authors.initials: E
authors.lastname: Speicher
authors.forename: Marie
authors.initials: M
authors.lastname: Fouts
authors.forename: Doug
authors.initials: D
authors.lastname: Larson
authors.forename: Mohamad
authors.initials: M
authors.lastname: Azhar
authors.forename: Urs
authors.initials: U
authors.lastname: Utzinger
authors.forename: Jonathan
authors.initials: J
authors.lastname: Vande Geest
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000378:metabolism; D001696:Biomechanical Phenomena; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001057:Apolipoproteins E; D000804:Angiotensin II; D003094:Collagen