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

Haskett, Darren; Speicher, Erin; Fouts, Marie; Larson, Doug; Azhar, Mohamad; Utzinger, Urs; Geest, Jonathan Vande

doi:10.1016/j.jbiomech.2011.11.017

Cited by 20 publications

(24 citation statements)

References 38 publications

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“…To quantify the model fit, we calculated R 2 using a nonlinear formulation and further verified the fit by calculating an adjusted R 2 since a larger number of model parameters often gives a better fit (Zeinali-Davarani et al, 2009). The phenomenological model identified strain-induced stiffening evident by an average

R_{italicadj}^{2} = 0.89

, which is the same or higher than the non-adjusted R 2 values calculated for the same exponential model in other studies (Fung et al, 1979; Haskett et al, 2012). For control and CTEPH tissues, we found that the model fit the circumferential direction better than the axial direction (Table 1).…”

Section: Discussionsupporting

confidence: 69%

“…We investigated the ability of a phenomenological exponential Fung-type strain energy function (W) (Fung et al, 1979; Hansen et al, 2009; Haskett et al, 2012; Keyes et al, 2011) to differentiate between strain-and remodeling-induced PA stiffening:

W = \frac{c}{2} (e^{Q} - 1)

Q = a_{1} E_{θ}^{2} + a_{2} E_{z}^{2} + 2 a_{12} E_{θ} E_{z}

where the stress parameter (c) is associated with the slope of the mechanical response, and the material parameters (a 1 , a 2 , and a 12 ) govern the shape of the stress response. Data from circumferential and axial strips from the same tissue were simultaneously fit to the model as previously demonstrated with uniaxial data (Holzapfel, 2006; Kao et al, 2011).…”

Section: Methodsmentioning

confidence: 99%

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Pulmonary arterial strain- and remodeling-induced stiffening are differentiated in a chronic model of pulmonary hypertension

Golob

Tabima

Wolf

et al. 2017

Journal of Biomechanics

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Pulmonary hypertension (PH) is a debilitating vascular disease that leads to pulmonary artery (PA) stiffening, which is a predictor of patient mortality. During PH development, PA stiffening adversely affects right ventricular function. PA stiffening has been investigated through the arterial nonlinear elastic response during mechanical testing using a canine PH model. However, only circumferential properties were reported and in the absence of chronic PH-induced PA remodeling. Remodeling can alter arterial nonlinear elastic properties via chronic changes in extracellular matrix (ECM) content and geometry. Here, we used an established constitutive model to demonstrate and differentiate between strain-induced stiffening, which is due to nonlinear elasticity, and remodeling-induced stiffening, which is due to ECM and geometric changes, in a canine model of chronic thromboembolic PH (CTEPH). To do this, circumferential and axial tissue strips of large extralobar PAs from control and CTEPH tissues were tested in uniaxial tension, and data were fit to a phenomenological constitutive model. Strain-induced stiffening was evident from mechanical testing as nonlinear elasticity in both directions and computationally by a high correlation coefficient between the mechanical data and model (R2=0.89). Remodeling-induced stiffening was evident from a significant increase in the constitutive model stress parameter, which correlated with increased PA collagen content and decreased PA elastin content as measured histologically. The ability to differentiate between strain- and remodeling-induced stiffening in vivo may lead to tailored clinical treatments for PA stiffening in PH patients.

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R_{italicadj}^{2} = 0.89

Section: Discussionsupporting

confidence: 69%

W = \frac{c}{2} (e^{Q} - 1)

Q = a_{1} E_{θ}^{2} + a_{2} E_{z}^{2} + 2 a_{12} E_{θ} E_{z}

Section: Methodsmentioning

confidence: 99%

Pulmonary arterial strain- and remodeling-induced stiffening are differentiated in a chronic model of pulmonary hypertension

Golob

Tabima

Wolf

et al. 2017

Journal of Biomechanics

View full text Add to dashboard Cite

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“…(3)) could be replaced with a recruitment model (e.g., Ref. [70]), which would provide an alternative mechanism to capture the nonlinear behavior associated with fiber waviness [71] and might provide a better fit of the experimental data. All of these modifications are possible and could be implemented as additional data emerge about the arrangement and properties of the components of the arterial wall.…”

Section: Discussionmentioning

confidence: 99%

Failure of the Porcine Ascending Aorta: Multidirectional Experiments and a Unifying Microstructural Model

Witzenburg

Dhume

Shah

et al. 2017

Journal of Biomechanical Engineering

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The ascending thoracic aorta is poorly understood mechanically, especially its risk of dissection. To make better predictions of dissection risk, more information about the multidimensional failure behavior of the tissue is needed, and this information must be incorporated into an appropriate theoretical/computational model. Toward the creation of such a model, uniaxial, equibiaxial, peel, and shear lap tests were performed on healthy porcine ascending aorta samples. Uniaxial and equibiaxial tests showed anisotropy with greater stiffness and strength in the circumferential direction. Shear lap tests showed catastrophic failure at shear stresses (150-200 kPa) much lower than uniaxial tests (750-2500 kPa), consistent with the low peel tension ($60 mN/mm). A novel multiscale computational model, including both prefailure and failure mechanics of the aorta, was developed. The microstructural part of the model included contributions from a collagenreinforced elastin sheet and interlamellar connections representing fibrillin and smooth muscle. Components were represented as nonlinear fibers that failed at a critical stretch. Multiscale simulations of the different experiments were performed, and the model, appropriately specified, agreed well with all experimental data, representing a uniquely complete structure-based description of aorta mechanics. In addition, our experiments and model demonstrate the very low strength of the aorta in radial shear, suggesting an important possible mechanism for aortic dissection.

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“…While previous studies in our lab 12 and other others such as Collins et al 11 and Fujikura et al 18 have used wild-type C57BL/6 mice to look into the mechanical properties of the mouse aorta to gain a more complete picture of underlying properties of vessel response, these studies did not include specimens from the actual ApoE AngII infused aneurysm model. And although Collins et al reported some histology, absent in both their work and that of Fujikura et al is analysis of fiber microstructure simultaneously with biomechanical response.…”

Section: Discussionmentioning

confidence: 99%

“…Also of importance, is the need to couple any biomechanical modeling with changes in extracellular matrix and associated alterations in microstructure. Recent work has started to address this by first defining the mechanical properties and constitutive modeling of wild-type (C57BL/6) mice 11 , 12 . However, these studies do not include the actual the ApoE −/− AngII infused model of AAA.…”

Section: Introductionmentioning

confidence: 99%

Progressive alterations in microstructural organization and biomechanical response in the ApoE mouse model of aneurysm

et al. 2013

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AAA is a complex disease that leads to a localized dilation of the infrarenal aorta that develops over years. Longitudinal information in humans has been difficult to obtain for this disease, therefore mouse models have become increasingly used to study the development of AAAs. The objective of this study was to determine any changes that occur in the biomechanical response and fiber microstructure in the ApoE−/− AngII mouse model of aneurysm during disease progression. Adult ApoE−/− AngII infused mice along with wild-type controls were taken at 14 and 28 d. Aortas were excised and tested simultaneously for biaxial mechanical response and ECM organization. Data sets were fit to a Fung-type constitutive model to give peak strains and stiffness values. Images from two photon microscopy were quantified in order to assess the preferred fiber alignment and degree of fiber orientation. Biomechanical results found significant differences that were present at 14 d had returned to normal by 28 d along with significant changes in fiber orientation and dispersion indicating remodeling occurring within the aneurysmal wall. This return of some of the normal biomechanical function, in addition the continuing changes that occur in the microstructure suggest a restorative response that occurs in the ApoE−/− AngII infused model after the initial aneurysm formation.

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

Cited by 20 publications

References 38 publications

Pulmonary arterial strain- and remodeling-induced stiffening are differentiated in a chronic model of pulmonary hypertension

Pulmonary arterial strain- and remodeling-induced stiffening are differentiated in a chronic model of pulmonary hypertension

Failure of the Porcine Ascending Aorta: Multidirectional Experiments and a Unifying Microstructural Model

Progressive alterations in microstructural organization and biomechanical response in the ApoE mouse model of aneurysm

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