Metabolic heterogeneity of proteoglycans from arterial wall

• 1.1. Four pools of proteoglycans were isolated by sequential extraction from pig arterial wall. They exhibited great metabolic and chemical heterogeneity.
• 2.2. Proteoglycans extracted by 4 M guanidinium chloride showed the highest labeling rate; and among the different glycosaminoglycans chains, the highest incorporation was measured in heparan sulfate chains.
• 3.3. Pulse chase experiments gave some evidence of precursor product relation between insoluble or less soluble, intracellular proteoglycans and the other soluble proteoglycans of the matrix.

     

Effects of arterial wall stress on vasomotion

Smooth muscle and endothelial cells in the arterial wall are exposed to mechanical stress. Indeed blood flow induces intraluminal pressure variations and shear stress. An increase in pressure may induce a vessel contraction, a phenomenon known as the myogenic response. Many muscular vessels present vasomotion, i.e., rhythmic diameter oscillations caused by synchronous cytosolic calcium oscillations of the smooth muscle cells. Vasomotion has been shown to be modulated by pressure changes. To get a better understanding of the effect of stress and in particular pressure on vasomotion, we propose a model of a blood vessel describing the calcium dynamics in a coupled population of smooth muscle cells and endothelial cells and the consequent vessel diameter variations. We show that a rise in pressure increases the calcium concentration. This may either induce or abolish vasomotion, or increase its frequency depending on the initial conditions. In our model the myogenic response is less pronounced for large arteries than for small arteries and occurs at higher values of pressure if the wall thickness is increased. Our results are in agreement with experimental observations concerning a broad range of vessels.     

Alternate method for the analysis of residual strain in the arterial wall

If an artery is cut transversely into rings, and the rings are then cut radially, they spring open into sectors. This phenomenon implies the existence of residual stresses and strains in the arterial wall in the non-loaded state. In the present paper, we propose a new method to calculate the residual strain from the measured wall dimensions and a polar angle of a specimen in the stress-free state, assuming that the wall is homogeneous and incompressible, and that a radially cut, stress-free specimen forms a circular sector. For this analysis, edge angles were measured at the edges of the opened-up specimen. Residual strains were obtained for the descending thoracic aorta, the common carotid artery, and the femoral artery in the rabbit. The results obtained indicated that the magnitude of residual strain was largest in the femoral artery and smallest in the aorta among the three arteries. The opening angle did not depend upon the length of a ring specimen if the ratio of the length to the diameter was ≤ 3.     

Stress-modulated growth, residual stress, and vascular heterogeneity.

A simple phenomenological model is used to study interrelations between material properties, growth-induced residual stresses, and opening angles in arteries. The artery is assumed to be a thick-walled tube composed of an orthotropic pseudoelastic material. In addition, the normal mature vessel is assumed to have uniform circumferential wall stress, which is achieved here via a mechanical growth law. Residual stresses are computed for three configurations: the unloaded intact artery, the artery after a single transmural cut, and the inner and outer rings of the artery created by combined radial and circumferential cuts. The results show that the magnitudes of the opening angles depend strongly on the heterogeneity of the material properties of the vessel wall and that multiple radial and circumferential cuts may be needed to relieve all residual stress. In addition, comparing computed opening angles with published experimental data for the bovine carotid artery suggests that the material properties change continuously across the vessel wall and that stress, not strain, correlates well with growth in arteries.     

Bioinjection treatment: Effects of post-injection residual stress on left ventricular wall stress

Injection of biomaterials into diseased myocardium has been associated with decreased myofiber stress, restored left ventricular (LV) geometry and improved LV function. However, its exact mechanism(s) of action remained unclear. In this work, we present the first patient-specific computational model of biomaterial injection that accounts for the possibility of residual strain and stress introduced by this treatment. We show that the presence of residual stress can create more heterogeneous regional myofiber stress and strain fields. Our simulation results show that the treatment generates low stress and stretch areas between injection sites, and high stress and stretch areas between the injections and both the endocardium and epicardium. Globally, these local changes are translated into an increase in average myofiber stress and its standard deviation (from 6.9±4.6 to 11.2±48.8 kPa and 30±15 to 35.1±50.9 kPa at end-diastole and end-systole, respectively). We also show that the myofiber stress field is sensitive to the void-to-size ratio. For a constant void size, the myofiber stress field became less heterogeneous with decreasing injection volume. These results suggest that the residual stress and strain possibly generated by biomaterial injection treatment can have large effects on the regional myocardial stress and strain fields, which may be important in the remodeling process.     

Branching exponent heterogeneity and wall shear stress distribution in vascular trees

A bifurcating arterial system with Poiseuille flow can function at minimum cost and with uniform wall shear stress if the branching exponent (z) = 3 [where z is defined by (D(1))(z) = (D(2))(z) + (D(3))(z); D(1) is the parent vessel diameter and D(2) and D(3) are the two daughter vessel diameters at a bifurcation]. Because wall shear stress is a physiologically transducible force, shear stress-dependent control over vessel diameter would appear to provide a means for preserving this optimal structure through maintenance of uniform shear stress. A mean z of 3 has been considered confirmation of such a control mechanism. The objective of the present study was to evaluate the consequences of a heterogeneous distribution of z values about the mean with regard to this uniform shear stress hypothesis. Simulations were carried out on model structures otherwise conforming to the criteria consistent with uniform shear stress when z = 3 but with varying distributions of z. The result was that when there was significant heterogeneity in z approaching that found in a real arterial tree, the coefficient of variation in shear stress was comparable to the coefficient of variation in z and nearly independent of the mean value of z. A systematic increase in mean shear stress with decreasing vessel diameter was one component of the variation in shear stress even when the mean z = 3. The conclusion is that the influence of shear stress in determining vessel diameters is not, per se, manifested in a mean value of z. In a vascular tree having a heterogeneous distribution in z values, a particular mean value of z (e.g., z = 3) apparently has little bearing on the uniform shear stress hypothesis.     

Effect of furosemide on the ionic composition of the arterial wall

Furosemide decreased the intracellular H2O, Cl and K content and Cl concentration of dog carotid arteries incubated in normal or high K Krebs (123 mM). Cl loss exceeded K loss in normal Krebs but was of the same magnitude in high K Krebs. The findings are compatible with the inhibition of a neutral K-Cl coupled uptake.     

A boundary layer model for wall shear stress in arterial stenosis

This paper proposes a model for wall shear stress in arterial stenosis based on boundary layer theory. Wall shear stress estimates are obtained by solving the momentum integral equation using the method proposed by Walz and applying this method to various stenosis geometries for Reynolds numbers (Re) of Re = 59-1000. Elevated wall shear stress may be of importance when considering thrombosis and vascular erosion in stenosis, as well as the potential for debris from the stenotic area to 'break away' and cause further pathology. The values of shear stress obtained using the model in this study agree well with published values of wall shear stress. When compared to a previously published boundary layer model utilizing the Thwaites method (Reese and Thompson, 1998), the model proposed herein performs better at higher Re while the model utilizing the Thwaites method performs better at lower Re. Wall shear stresses are shown to increase with increasing stenosis (increased area reduction) for a given stenosis length, increase with increasing Re for a given stenosis geometry, and increase for steeper stenosis of the same constriction. The boundary layer model proposed can be easily implemented by clinical researchers to provide in vivo estimates of wall shear stress through arterial stenoses.     

Effects of transmural pressure and wall shear stress on LDL accumulation in the arterial wall: a numerical study using a multilayered model

The accumulation of low-density lipoprotein (LDL) is recognized as one of the main contributors in atherogenesis. Mathematical models have been constructed to simulate mass transport in large arteries and the consequent lipid accumulation in the arterial wall. The objective of this study was to investigate the influences of wall shear stress and transmural pressure on LDL accumulation in the arterial wall by a multilayered, coupled lumen-wall model. The model employs the Navier-Stokes equations and Darcy's Law for fluid dynamics, convection-diffusion-reaction equations for mass balance, and Kedem-Katchalsky equations for interfacial coupling. To determine physiologically realistic model parameters, an optimization approach that searches optimal parameters based on experimental data was developed. Two sets of model parameters corresponding to different transmural pressures were found by the optimization approach using experimental data in the literature. Furthermore, a shear-dependent hydraulic conductivity relation reported previously was adopted. The integrated multilayered model was applied to an axisymmetric stenosis simulating an idealized, mildly stenosed coronary artery. The results show that low wall shear stress leads to focal LDL accumulation by weakening the convective clearance effect of transmural flow, whereas high transmural pressure, associated with hypertension, leads to global elevation of LDL concentration in the arterial wall by facilitating the passage of LDL through wall layers.     

Effect of food intake on left ventricular wall stress

Objective

Left ventricular wall stress has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether left ventricular wall stress is affected by food intake in healthy subjects.

Methods

Twenty-three healthy subjects aged 25.6?±?4.5 years were investigated. Meridional end-systolic wall stress (ESS) and circumferential end-systolic wall stress (cESS) were measured before, 30 minutes after, and 110 minutes after a standardised meal.

Results

Both ESS and cESS decreased significantly (P?<?0.001) from fasting values 30 minutes after the meal, and had not returned to baseline after 110 minutes. ESS decreased from 65?±?16 kdynes/cm² (fasting) to 44?±?12 kdynes/cm² 30 minutes after, and to 58?±?13 kdynes/cm² 110 minutes after eating. cESS decreased from 98?±?24 kdynes/cm² to 67?±?18 kdynes/cm² 30 minutes after, and to 87?±?19 kdynes/cm² 110 minutes after the meal.

Conclusion

This study shows that left ventricular wall stress is affected by food intake in healthy subjects.     

Spatial comparison between wall shear stress measures and porcine arterial endothelial permeability

A better understanding of how hemodynamic factors affect the integrity and function of the vascular endothelium is necessary to appreciate more fully how atherosclerosis is initiated and promoted. A novel technique is presented to assess the relation between fluid dynamic variables and the permeability of the endothelium to macromolecules. Fully anesthetized, domestic swine were intravenously injected with the albumin marker Evans blue dye, which was allowed to circulate for 90 min. After the animals were euthanized, silicone casts were made of the abdominal aorta and its iliac branches. Pulsatile flow calculations were subsequently made in computational regions derived from the casts. The distribution of the calculated time-dependent wall shear stress in the external iliac branches was directly compared on a point-by-point basis with the spatially varying in vivo uptake of Evans blue dye in the same arteries. The results indicate that in vivo endothelial permeability to albumin decreases with increasing time-average shear stress over the normal range. Additionally, endothelial permeability increases slightly with oscillatory shear index.     

Effect of circumferential heterogeneity of wood maturation strain, modulus of elasticity and radial growth on the regulation of stem orientation in trees

Active mechanisms of re-orientation are necessary to maintain the verticality of tree stems. They are achieved through the production of reaction wood, associated with circumferential variations of three factors related to cambial activity: maturation strain, longitudinal modulus of elasticity (MOE) and eccentric growth. These factors were measured on 17 mature trees from different botanical families and geographical locations. Various patterns of circumferential variation of these factors were identified. A biomechanical analysis based on beam theory was performed to quantify the individual impact of each factor. The main factor of re-orientation is the circumferential variation of maturation strains. However, this factor alone explains only 57% of the re-orientations. Other factors also have an effect through their interaction with maturation strains. Eccentric growth is generally associated with heterogeneity of maturation strains, and has an important complementary role, by increasing the width of wood with high maturation strain. Without this factor, the efficiency of re-orientations would be reduced by 31% for angiosperms and 26% for gymnosperms. In the case of angiosperms, MOE is often larger in tension wood than in normal wood. Without these variations, the efficiency of re-orientations would be reduced by 13%. In the case of gymnosperm trees, MOE of compression wood is lower than that of normal wood, so that re-orientation efficiency would be increased by 24% without this factor of variations.     

Maximal wall shear stress in arterial stenoses: application to the internal carotid arteries

Maximal wall shear stress (MWSS) in the convergent part of a stenosis is calculated by the interactive boundary-layer theory. A dimensional analysis of the problem shows that MWSS depends only on a few measurable parameters. A simple relationship between MWSS and these parameters is obtained, validated, and used to calculate the magnitude of MWSS in a carotid stenosis, as a function of the patency of the circle of Willis and the stenotic pattern. This demonstrates the huge effect of collateral pathways. Elevated MWSS are observed even in moderate stenoses, provided they are associated with a contralateral occlusion, a large anterior, and narrow posterior communicating arteries, suggesting a potential risk of embolus release in this configuration.     

Regional distribution of layer-specific circumferential residual deformations and opening angles in the porcine aorta

Information on the layer-specific residual deformations of aortic tissue and how these vary throughout the vessel is important for understanding the regionally-varying aortic functions and pathophysiology, but not so much can be found in the literature. Toward this end, porcine aortas were sectioned into eighteen rings, with one ring from each anatomical position radially cut to obtain the zero-stress state for the intact wall and the other ring dissected into intimal-medial and adventitial layers; these rings were then radially cut to reach the zero-stress state for the intima-media and adventitia. Peripheral variations in internal/external circumferences, thickness, and opening angle of the intact wall and its layers were measured through image analysis at the no-load and zero-stress states. Intact wall and layer circumferences at both states significantly declined along the aorta, as did intact wall and intimal-medial but not adventitial thickness. Adventitia exhibited the greatest opening angles, approaching 180 deg all over the aorta. The opening angles of the intima-media and intact wall were quite similar, with the highest values in the ascending aorta, the lowest at the diaphragm, and increasing subsequently. Bending-related residual stretches were released by radial cutting that were compressive internally and tensile externally, displaying distinct axial variation for the intima-media and intact wall, and non-significant variation for the adventitia. Evidence is provided for the release upon layer separation of compressive stretches in the intima-media and of tensile stretches in the adventitia, whose values were smallest in the descending thoracic aorta and highest near the iliac artery bifurcation.     

Regional distribution of axial strain and circumferential residual strain in the layered rabbit oesophagus

The oesophagus is subjected to large axial strains in vivo and the zero-stress state is not a closed cylinder but an open circular cylindrical sector. The closed cylinder with no external loads applied is called the no-load state and residual strain is the difference in strain between the no-load state and zero-stress state. To understand oesophageal physiology and pathophysiology, it is necessary to know the distribution of axial strain, the zero-stress state, the stress-strain relations of oesophageal tissue, and the changes of these states and relationships due to biological remodeling of the tissue under stress. This study is addressed to such biomechanical properties in normal rabbits. The oesophagi were marked on the surface in vivo, photographed, excised (in vitro state), photographed again, and sectioned into rings (no-load state) in an organ bath containing calcium-free Kreb's solution with dextran and EGTA added. The rings were cut radially to obtain the zero-stress state for the non-separated wall and further dissected to separate the muscle and submucosa layers. Equilibrium was awaited for 30min in each state and the specimens were photographed in no-load and the zero-stress states. The oesophageal length, circumferences, layer thicknesses and areas, and openings angle were measured from the digitised images. The oesophagus shortened axially by 35% after excision. The in vivo axial strain showed a significant variation with the highest values in the mid-oesophagus (p<0.001). Luminal area, circumferences, and wall and layer thicknesses and areas varied in axial direction (in all tests p<0.05). The residual strain was compressive at the mucosal surface and tensile at the serosal surface. The dissection studies demonstrated shear forces between the two layers in the non-separated wall in the no-load and zero-stress states. In conclusion, our data show significant axial variation in passive morphometric and biomechanical properties of the oesophagus. The oesophagus is a layered composite structure with nonlinear and anisotropic mechanical behaviour.     

Markers of inflammation collocate with increased wall stress in human coronary arterial plaque

In this study, we hypothesized that spatial relationships exist between the local mechanical environment and inflammatory marker expression in atherosclerotic plaques, and that these relationships are plaque-progression dependent. Histologic cross-sections were collected at regular intervals along the length of diseased human coronary arteries and classified as early, intermediate, advanced, or mature based on their morphological features. For each cross-section, the spatial distribution of stress was determined using a 2D heterogeneous finite element model, and the corresponding distribution of selected inflammatory markers (macrophages, matrix metalloproteinase-1 [MMP-1], and nuclear factor-kappa B [NF-κB]) were determined immunohistochemically. We found a monotonic spatial relationship between mechanical stress and activated NF-κB that was consistent in all stages of plaque progression. We also identified progression-dependent relationships between stress and both macrophage presence and MMP-1 expression. These findings add to our understanding of the role of mechanical stress in stimulating the inflammatory response, and help explain how mechanical factors may regulate complex biological changes in remodeling.