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1. Diet alters age-related remodeling of aortic collagen in mice susceptible to atherosclerosis

   https://doi.org/10.1152/ajpheart.00420.2020  

   Watson, Shana R. ; Cooper, Kara M. ; Liu, Piaomu ; Gharraee, Nazli ; Du, Liya ; Han, Savannah M. ; Peña, Edsel A. ; Sutton, Michael A. ; Eberth, John F. ; Lessner, Susan M. ( January 2021 , American Journal of Physiology-Heart and Circulatory Physiology)

   Vascular cells restructure extracellular matrix in response to aging or changes in mechanical loading. Here, we characterized collagen architecture during age-related aortic remodeling in atherosclerosis-prone mice. We hypothesized that changes in collagen fiber orientation reflect an altered balance between passive and active forces acting on the arterial wall. We examined two factors that can alter this balance, endothelial dysfunction and reduced smooth muscle cell (SMC) contractility. Collagen fiber organization was visualized by second-harmonic generation microscopy in aortic adventitia of apolipoprotein E (apoE) knockout (KO) mice at 6 wk and 6 mo of age on a chow diet and at 7.5 mo of age on a Western diet (WD), using image analysis to yield mean fiber orientation. Adventitial collagen fibers became significantly more longitudinally oriented with aging in apoE knockout mice on chow diet. Conversely, fibers became more circumferentially oriented with aging in mice on WD. Total collagen content increased significantly with age in mice fed WD. We compared expression of endothelial nitric oxide synthase and acetylcholine-mediated nitric oxide release but found no evidence of endothelial dysfunction in older mice. Time-averaged volumetric blood flow in all groups showed no significant changes. Wire myography of aortic rings revealed decreases in active stress generation with agemore »that were significantly exacerbated in WD mice. We conclude that the aorta displays a distinct remodeling response to atherogenic stimuli, indicated by altered collagen organization. Collagen reorganization can occur in the absence of altered hemodynamics and may represent an adaptive response to reduced active stress generation by vascular SMCs. NEW & NOTEWORTHY The following major observations were made in this study: 1) aortic adventitial collagen fibers become more longitudinally oriented with aging in apolipoprotein E knockout mice fed a chow diet; 2) conversely, adventitial collagen fibers become more circumferentially oriented with aging in apoE knockout mice fed a high-fat diet; 3) adventitial collagen content increases significantly with age in mice on a high-fat diet; 4) these alterations in collagen organization occur largely in the absence of hemodynamic changes; and 5) circumferential reorientation of collagen is associated with decreased active force generation (contractility) in aged mice on a high-fat diet.« less
2. Reduced Smooth Muscle Contractile Capacity Facilitates Maladaptive Arterial Remodeling

   https://doi.org/10.1115/1.4052888  

   Eberth, John F. ; Humphrey, Jay D. ( April 2022 , Journal of Biomechanical Engineering)

   Abstract Albeit seldom considered explicitly, the vasoactive state of a central artery can contribute to luminal control and thereby affect the in vivo values of flow-induced wall shear stress and pressure-induced intramural stress, which in turn are strong determinants of wall growth and remodeling. Here, we test the hypothesis that diminished vasoactive capacity compromises effective mechano-adaptations of central arteries. Toward this end, we use consistent methods to re-interpret published data on common carotid artery remodeling in a nonpharmacologic mouse model of induced hypertension and a model of connective tissue disorder that results in Marfan syndrome. The mice have identical genetic backgrounds and, in both cases, the data are consistent with the hypothesis considered. In particular, carotid arteries with strong (normal) vasoactive capacity tend to maintain wall thickness and in vivo axial stretch closer to homeostatic, thus resulting in passive circumferential wall stress and energy storage close to normal. We conclude that effective vasoactivity helps to control the biomechanical state in which the cells and matrix turnover, thus helping to delineate mechano-adaptive from maladaptive remodeling. Future analyses of experimental data and computational models of growth and remodeling should account for this strong coupling between smooth muscle contractile capacity and central arterialmore »remodeling.« less
3. Biaxial Murine Vaginal Remodeling With Reproductive Aging

   https://doi.org/10.1115/1.4054362  

   White, Shelby E. ; Kiley, Jasmine X. ; Visniauskas, Bruna ; Lindsey, Sarah H. ; Miller, Kristin S. ( June 2022 , Journal of Biomechanical Engineering)

   Abstract Higher reproductive age is associated with an increased risk of gestational diabetes, pre-eclampsia, and severe vaginal tearing during delivery. Further, menopause is associated with vaginal stiffening. However, the mechanical properties of the vagina during reproductive aging before the onset of menopause are unknown. Therefore, the first objective of this study was to quantify the biaxial mechanical properties of the nulliparous murine vagina with reproductive aging. Menopause is further associated with a decrease in elastic fiber content, which may contribute to vaginal stiffening. Hence, our second objective was to determine the effect of elastic fiber disruption on the biaxial vaginal mechanical properties. To accomplish this, vaginal samples from CD-1 mice aged 2–14 months underwent extension-inflation testing protocols (n = 64 total; n = 16/age group). Then, half of the samples were randomly allocated to undergo elastic fiber fragmentation via elastase digestion (n = 32 total; 8/age group) to evaluate the role of elastic fibers. The material stiffness increased with reproductive age in both the circumferential and axial directions within the control and elastase-treated vaginas. The vagina demonstrated anisotropic mechanical behavior, and anisotropy increased with age. In summary, vaginal remodeling with reproductive age included increased direction-dependent material stiffness, which further increased following elastic fiber disruption. Further work ismore »needed to quantify vaginal remodeling during pregnancy and postpartum with reproductive aging to better understand how age-related vaginal remodeling may contribute to an increased risk of vaginal tearing.« less
4. Distinct time courses and mechanics of right ventricular hypertrophy and diastolic stiffening in a male rat model of pulmonary arterial hypertension

   https://doi.org/10.1152/ajpheart.00046.2021  

   Kwan, Ethan D. ; Vélez-Rendón, Daniela ; Zhang, Xiaoyan ; Mu, Hao ; Patel, Megh ; Pursell, Erica ; Stowe, Jennifer ; Valdez-Jasso, Daniela ( October 2021 , American Journal of Physiology-Heart and Circulatory Physiology)

   Although pulmonary arterial hypertension (PAH) leads to right ventricle (RV) hypertrophy and structural remodeling, the relative contributions of changes in myocardial geometric and mechanical properties to systolic and diastolic chamber dysfunction and their time courses remain unknown. Using measurements of RV hemodynamic and morphological changes over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we discriminated the contributions of RV geometric remodeling and alterations of myocardial material properties to changes in systolic and diastolic chamber function. Significant and rapid RV hypertrophic wall thickening was sufficient to stabilize ejection fraction in response to increased pulmonary arterial pressure by week 4 without significant changes in systolic myofilament activation. After week 4, RV end-diastolic pressure increased significantly with no corresponding changes in end-diastolic volume. Significant RV diastolic chamber stiffening by week 5 was not explained by RV hypertrophy. Instead, model analysis showed that the increases in RV end-diastolic chamber stiffness were entirely attributable to increased resting myocardial material stiffness that was not associated with significant myocardial fibrosis or changes in myocardial collagen content or type. These findings suggest that whereas systolic volume in this model of RV pressure overload is stabilized by early RV hypertrophy,more »diastolic dilation is prevented by subsequent resting myocardial stiffening. NEW & NOTEWORTHY Using a novel combination of hemodynamic and morphological measurements over 10 wk in a male rat model of PAH and a mathematical model of RV mechanics, we found that compensated systolic function was almost entirely explained by RV hypertrophy, but subsequently altered RV end-diastolic mechanics were primarily explained by passive myocardial stiffening that was not associated with significant collagen extracellular matrix accumulation.« less
5. Tunable elastomer materials with vascular tissue-like rupture mechanics behavior

   https://doi.org/10.1088/2057-1976/ac82f6  

   Corti, Andrea ; Shameen, Tariq ; Sharma, Shivang ; De Paolis, Annalisa ; Cardoso, Luis ( August 2022 , Biomedical Physics & Engineering Express)

   Abstract Purpose . Laboratory models of human arterial tissues are advantageous to examine the mechanical response of blood vessels in a simplified and controllable manner. In the present study, we investigated three silicone-based materials for replicating the mechanical properties of human arteries documented in the literature. Methods . We performed uniaxial tensile tests up to rupture on Sylgard184, Sylgard170 and DowsilEE-3200 under different curing conditions and obtained their True (Cauchy) stress-strain behavior and Poisson’s ratios by means of digital image correlation (DIC). For each formulation, we derived the constitutive parameters of the 3-term Ogden model and designed numerical simulations of tubular models under a radial pressure of 250 mmHg. Results . Each material exhibits evident non-linear hyperelasticity and dependence on the curing condition. Sylgard184 is the stiffest formulation, with the highest shear moduli and ultimate stresses at relative low strains ( μ 184  = 0.52–0.88 MPa, σ 184  = 15.90–16.54 MPa, ε 184  = 0.72–0.96). Conversely, Sylgard170 and DowsilEE-3200 present significantly lower shear moduli and ultimate stresses that are closer to data reported for arterial tissues ( μ 170  = 0.33–0.7 MPa σ 170  = 2.61–3.67 MPa, ε 170  = 0.69–0.81; μ dow = 0.02–0.09 MPa σ dow = 0.83–2.05 MPa, ε dow = 0.91–1.05). Undermore »radial pressure, all formulations except DowsilEE-3200 at 1:1 curing ratio undergo circumferential stresses that remain in the elastic region with values ranging from 0.1 to 0.18 MPa. Conclusion . Sylgard170 and DowsilEE-3200 appear to better reproduce the rupture behavior of vascular tissues within their typical ultimate stress and strain range. Numerical models demonstrate that all three materials achieve circumferential stresses similar to human common carotid arteries (Sommer et al 2010), making these formulations suited for cylindrical laboratory models under physiological and supraphysiological loading.« less