A fiber-based constitutive model predicts changes in amount and organization of matrix proteins with development and disease in the mouse aorta

Abstract

Decreased elastin in mice (Eln+/−) yields a functioning vascular system with elevated blood pressure and increased arterial stiffness that is morphologically distinct from wild-type mice (WT). Yet, function is retained enough that there is no appreciable effect on life span and some mechanical properties are maintained constant. It is not understood how the mouse modifies the normal developmental process to produce a functioning vascular system despite a deficiency in elastin. To quantify changes in mechanical properties, we have applied a fiber-based constitutive model to mechanical data from the ascending aorta during postnatal development of WT and Eln+/− mice. Results indicate that the fiber-based constitutive model is capable of distinguishing elastin amounts and identifying trends during development. We observe an increase in predicted circumferential stress contribution from elastin with age, which correlates with increased elastin amounts from protein quantification data. The model also predicts changes in the unloaded collagen fiber orientation with age, which must be verified in future work. In Eln+/− mice, elastin amounts are decreased at each age, along with the predicted circumferential stress contribution of elastin. Collagen amounts in Eln+/− aorta are comparable to WT, but the predicted circumferential stress contribution of collagen is increased. This may be due to altered organization or structure of the collagen fibers. Relating quantifiable changes in arterial mechanics with changes in extracellular matrix (ECM) protein amounts will help in understanding developmental remodeling and in producing treatments for human diseases affecting ECM proteins.

Towards the modelling of ageing and atherosclerosis effects in ApoE-/- mice aortic tissue

“…Similar results were obtained by [6], they applied a fiber-based constitutive model to mechanical data from aorta during postnatal development of WT and Eln+/-mice and obtained the model was capable of distinguishing elastin amounts and identifying trends during development. Regarding the temporal evolution of the material parameters, we observe significant deviations of the material parameters between the ApoE −/− and the control mice as well as for the different locations over the aorta (upper, lower, iliac) which clearly underlined our observations from the experiments.…”

Quantification of the passive and active biaxial mechanical behaviour and microstructural organization of rat thoracic ducts

“…First, although elastin is often modelled as an isotropic material [25,[30][31][32], qualitative observations of elastin orientation suggested nearly circumferentially and nearly axially oriented fibres. Second, although we did not quantify their organization, there are nearly circumferentially oriented smooth muscle cells.…”

Effects of aging on the architecture of the ileocecal junction in rats

“…This finding suggests that changes in the distribution of collagen fibers could damage the function of the submucosal ganglia. Also, authors reported an increase in the number of collagen fibers in the aorta of aged mice [41] . In addition, authors showed that aging favored an increase in the diameter of collagen fibrils [42] , in agreement with our findings.…”