The effects of angiotensin II on the coupled microstructural and biomechanical response of C57BL/6 mouse aorta

Darren Haskett, Erin Speicher, Marie Fouts, Douglas F Larson, Mohamad Azhar, Urs Utzinger, Jonathan P Vande Geest

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Rationale: 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.

Original languageEnglish (US)
Pages (from-to)772-779
Number of pages8
JournalJournal of Biomechanics
Volume45
Issue number5
DOIs
StatePublished - Mar 15 2012

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Inbred C57BL Mouse
Angiotensin II
Aorta
Collagen
Fibers
Stiffness
Adventitia
Microscopic examination
Animals
Abdominal Aortic Aneurysm
Full width at half maximum
Constitutive models
Compliance
Photons
Dilatation
Microscopy
Tissue
Equipment and Supplies
Apolipoproteins E
Aneurysm

Keywords

  • Aneurysm
  • AngII
  • Angiotensin
  • Aorta
  • Microstructure
  • Mouse
  • Multiphoton
  • Two-photon

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Rehabilitation
  • Biophysics
  • Biomedical Engineering

Cite this

The effects of angiotensin II on the coupled microstructural and biomechanical response of C57BL/6 mouse aorta. / Haskett, Darren; Speicher, Erin; Fouts, Marie; Larson, Douglas F; Azhar, Mohamad; Utzinger, Urs; Vande Geest, Jonathan P.

In: Journal of Biomechanics, Vol. 45, No. 5, 15.03.2012, p. 772-779.

Research output: Contribution to journalArticle

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abstract = "Rationale: 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.",
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