Morphological and Biomechanical Differences in the Elastase and AngIIapoE^−/−Rodent Models of Abdominal Aortic Aneurysms

Abstract

An abdominal aortic aneurysm (AAA) is a potentially fatal cardiovascular disease with multifactorial development and progression. Two preclinical models of the disease (elastase perfusion and angiotensin II infusion in apolipoprotein-E-deficient animals) have been developed to study the disease during its initiation and progression. To date, most studies have used ex vivo methods to examine disease characteristics such as expanded aortic diameter or analytic methods to look at circulating biomarkers. Herein, we provide evidence from in vivo ultrasound studies of the temporal changes occurring in biomechanical parameters and macromolecules of the aortic wall in each model. We present findings from 28-day studies in elastase-perfused rats and AngII apoE−/− mice. While each model develops AAAs specific to their induction method, they both share characteristics with human aneurysms, such as marked changes in vessel strain and blood flow velocity. Histology and nonlinear microscopy confirmed that both elastin and collagen, both important extracellular matrix molecules, are similarly affected in their levels and spatial distribution. Future studies could make use of the differences between these models in order to investigate mechanisms of disease progression or evaluate potential AAA treatments.

Polymer–iron oxide composite nanoparticles for EPR-independent drug delivery

“…Recent progress in the design of Halbach arrays indicate the possibility of producing sizable field gradients in tissue at depths of 10 cm, at much greater strengths than that produced by dipolar magnets of comparable size [36, 37]. With regard to locating tumors, high-resolution imaging of vascularized tissues is already addressable by MR as well as by ultrasound [38], photoacoustic tomography [39], and optical coherence tomography [40]. …”

Angiotensin II Infusion Does Not Cause Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Rats

“…This can be accomplished by computational fluid dynamic modeling to investigate how regional differences in flow patterns influence vascular growth and remodeling of the aorta [35,36]. We have previously shown how biomechanical and hemodynamic factors are influenced after AngII AAA formation in mice [23]. However, the role that hemodynamics [4,37,38] and biomechanics [39,40] play as an initiating factor for the disease requires further investigation in animal models and humans.…”

“…That being said, high-frequency US provides high resolution that is adequate to identify pathological expansion. In mice, AngII-induced AAAs are focal and saccular [8,23], which make them easy to distinguish from a healthy aorta. We did find that circumferential cyclic strain of the suprarenal aorta was reduced relative to baseline for all cohorts (Fig 5).…”

“…Rats used for histology (Cohorts 2a and 3) were pressure perfused through the left ventricle, as described previously [23]. We excised the heart and aorta and allowed them to fix in 4% paraformaldehyde for 24 hours.…”

An update on the etiology of abdominal aortic aneurysms: implications for future diagnostic testing

“…So far, no ideal model for AAA has been developed, so understanding the disease requires the use of these models in different combinations [87]; however, these models have helped validate the current genetic associations. The ideal model may come from novel combinations of chemical, physical and genetic models, but clearly more research into the genomics and expression profiles of aneurysmal patients will provide novel insight into the etiology and progression of AAA that can inform animal model development.…”