Heterogeneous transmural proteoglycan distribution provides a mechanism for regulating residual stresses in the aorta

Abstract

The arterial wall contains a significant amount of charged proteoglycans, which are inhomogeneously distributed, with the greatest concentrations in the intimal and medial layers. The hypothesis of this study is that the transmural distribution of proteoglycans plays a significant role in regulating residual stresses in the arterial wall. This hypothesis was first tested theoretically, using the framework of mixture theory for charged hydrated tissues, and then verified experimentally by measuring the opening angle of rat aorta in NaCl solutions of various ionic strengths. A three-dimensional finite element model of aortic ring, using realistic values of the solid matrix shear modulus and proteoglycan fixed-charge density, yielded opening angles and changes with osmolarity comparable to values reported in the literature. Experimentally, the mean opening angle in isotonic saline (300 mosM) was 15 +/- 17 degrees and changed to 4 +/- 19 degrees and 73 +/- 18 degrees under hypertonic (2,000 mosM) and hypotonic (0 mosM) conditions, respectively (n = 16). In addition, the opening angle in isotonic (300 mosM) sucrose, an uncharged molecule, was 60 +/- 16 degrees (n = 11), suggesting that the charge effect, not cellular swelling, was the major underlying mechanism for these observations. The extent of changes in opening angle under osmotic challenges suggests that transmural heterogeneity of fixed-charge density plays a crucial role in governing the zero-stress configuration of the aorta. A significant implication of this finding is that arterial wall remodeling in response to altered wall stresses may occur via altered deposition of proteoglycans across the wall thickness, providing a novel mechanism for regulating mechanical homeostasis in vascular tissue.

Constitutive modelling of arteries

“…One suggestion of a possible factor is contained in the recent study by Azeloglu et al (2008), in which it is hypothesized that the transmural distribution of the fixed charged density of the proteoglycans has a significant role in regulating residual stresses.…”

Fixed negative charge and the Donnan effect: a description of the driving forces associated with brain tissue swelling and oedema

“…To further determine whether the swelling behaviour of dead rat brain tissue could be modelled as a mixture material, equation (2.7) was used to predict free-swelling volume change (J − 1) as a function of ionic osmolarity (figure 5b; Lai et al 1991;Azeloglu et al 2008;Ateshian & Costa 2009). The reference state was considered to be the 4000 mOsm hypertonic group.…”

“…The total mixture stress, σ, was calculated assuming that the solid matrix can be described with isotropic Fung elasticity (Azeloglu et al 2008;Ateshian & Costa 2009) (2007)), J = √ detB is the relative volume and…”

Modeling the Matrix of Articular Cartilage Using a Continuous Fiber Angular Distribution Predicts Many Observed Phenomena

“…However, when entropic effects are present, there is no simple method to achieve the true reference configuration experimentally (p≠ 0, ∀ c̄*). 1 Since the osmotic pressure difference π = p− p * depends on the solid matrix deformation via the functional dependence p(J), there is an associated osmotic modulus that describes the resulting tissue stiffness, as presented in our recent study [34], 2 (5) Π is a fourth-order spatial elasticity tensor describing an isotropic material, as can be deduced from the general form of Eq. (5).…”