An experimental study on the ultimate strength of the adventitia and media of human atherosclerotic carotid arteries in circumferential and axial directions

Atherosclerotic plaque may rupture without warning causing heart attack or stroke. Knowledge of the ultimate strength of human atherosclerotic tissues is essential for understanding the rupture mechanism and predicting cardiovascular events. Despite its great importance, experimental data on ultimate strength of human atherosclerotic carotid artery remains very sparse. This study determined the uniaxial tensile strength of human carotid artery sections containing type II and III lesions (AHA classifications). Axial and circumferential oriented adventitia, media and intact specimens (total=73) were prepared from 6 arteries. The ultimate strength in uniaxial tension was taken as the peak stress recorded when the specimen showed the first evidence of failure and the extensibility was taken as the stretch ratio at failure. The mean adventitia strength values calculated using the first Piola–Kirchoff stress were 1996±867 and 1802±703 kPa in the axial and circumferential directions respectively, while the corresponding values for the media sections were 519±270 and 1230±533 kPa. The intact specimens showed ultimate strengths similar to media in circumferential direction but were twice as strong as the media in the axial direction. Results also indicated that adventitia, media and intact specimens exhibited similar extensibility at failure, in both the axial and circumferential directions (stretch ratio 1.50±0.22). These measurements of the material strength limits for human atherosclerotic carotid arteries could be useful in improving computational models that assess plaque vulnerability.     

Axial prestretch and circumferential distensibility in biomechanics of abdominal aorta

Elastic arteries are significantly prestretched in an axial direction. This property minimises axial deformations during pressure cycle. Ageing-induced changes in arterial biomechanics, among others, are manifested via a marked decrease in the prestretch. Although this fact is well known, little attention has been paid to the effect of decreased prestretch on mechanical response. Our study presents the results of an analytical simulation of the inflation–extension behaviour of the human abdominal aorta treated as nonlinear, anisotropic, prestrained thin-walled as well as thick-walled tube with closed ends. The constitutive parameters and geometries for 17 aortas adopted from the literature were supplemented with initial axial prestretches obtained from the statistics of 365 autopsy measurements. For each aorta, the inflation–extension response was calculated three times, with the expected value of the initial prestretch and with the upper and lower confidence limit of the initial prestretch derived from the statistics. This approach enabled age-related trends to be evaluated bearing in mind the uncertainty in the prestretch. Despite significantly decreased longitudinal prestretch with age, the biomechanical response of human abdominal aorta changes substantially depending on the initial axial stretch was used. In particular, substituting the upper limit of initial prestretch gave mechanical responses which can be characterised by (1) low variation in axial stretch and (2) high circumferential distensibility during pressurisation, in contrast to the responses obtained for their weakly prestretched counterparts. The simulation also suggested the significant effect of the axial prestretch on the variation of axial stress in the pressure cycle. Finally, the obtained results are in accordance with the hypothesis that circumferential-to-axial stiffness ratio is the quantity relatively constant within this cycle.     

Perivascular tethering modulates the geometry and biomechanics of cerebral arterioles

Recent studies have renewed interest in the effects of perivascular tethering on vascular mechanics, particularly growth and remodeling. We quantified effects of axial and circumferential tethering on rabbit pial arterioles from the ventral occipital lobe of the brain. The homeostatic axial pre-stretch, which is influenced by perivascular tethering, was measured in situ to be 1.24±0.04. Using a cannulated microvessel preparation, wall mechanics were then quantified in vitro for isolated arterioles at low (1.10) or normal (1.24) values of axial stretch and for tethered arterioles having perivascular support. Axial stretch did not significantly affect changes in circumferential stretch or stress upon pressurization, but circumferential tethering caused arteriolar geometry to change from a circular cross-section at normal pressure to an elliptical one at pressures above and below normal. Calculations suggested that the observed levels of ellipticity could cause a modest decrease in volumetric blood flow, but also a pronounced variation in shear stress around the circumference of the arteriole. An elliptical cross-section could thus increase vascular resistance or promote luminal remodeling at pressures different from normal. This characterization of effects of perivascular tethering on pial arterioles should prove useful in future studies of roles of perturbed cerebral blood flow on the propensity of the cerebral microcirculation to remodel.     

Viscoelastic properties of the passive mechanical behavior of the porcine carotid artery: Influence of proximal and distal positions

The viscoelastic properties of porcine carotid tissue are investigated in this work. Experimental uniaxial stress relaxation tests along the longitudinal and circumferential directions of the vessel were performed for carotid strips extracted from 10 vessels. Directional and local differences - distal versus proximal position - in the tissue behavior were investigated. The experimental tests reveal a highly anisotropic, non-linear viscoelastic response and local dependence of the samples. The carotid artery shows anisotropic relaxation behavior for both proximal and distal samples. The highest stress relaxation was found in the circumferential tensile test for the highest applied strain at the distal position. For the circumferential direction, the relaxation stress was higher than in the longitudinal being at its highest in the distal position. These facts show that the stress relaxation is higher in the distal than in the proximal position. However, there are no differences between both positions in the longitudinal direction. In addition, a constitutive law that takes into account the fundamental features, including non-linear viscoelasticity, of the arterial tissue is proposed. The present results are correlated with the purely elastic response and the microstructural analysis of the tissue by means of histological quantification presented in a previous study.     

Mechanical properties in the human gastric antrum using B-mode ultrasonography and antral distension

The aims of this study were to investigate gastric antral geometry and stress-strain properties by using transabdominal ultrasound scanning during volume-controlled distensions in the human gastric antrum. Seven healthy volunteers underwent stepwise inflation of a bag located in the antrum with volumes up to 60 ml. The stretch ratio and Cauchy stress and strain were calculated from measurements of pressure, diameter, and wall thickness. A second distension series was conducted in three volunteers during administration of the anticholinergic drug butylscopolamine. Analysis of stretch ratios demonstrated positive strain in the circumferential direction, negative strain in the radial direction, and no strain in the longitudinal direction. The stress-strain relation was exponential and did not differ without or with the administration of butylscopolamine. The wall stress was decomposed into its active and passive components. The well-known length-tension diagram from in vitro studies of smooth muscle strips was reproduced. The maximum active tension appeared at a volume of 50 ml, corresponding to a stretch ratio of 1.5. We conclude that the method provides measures of antral biomechanical wall properties and can be used to reproduce the muscle length-tension diagram in humans.     

Patient-Specific Artery Shrinkage and 3D Zero-Stress State in Multi-Component 3D FSI Models for Carotid Atherosclerotic Plaques Based on <i>In Vivo</i> MRI Data

Image-based computational models for atherosclerotic plaques have been developed to perform mechanical analysis to quantify critical flow and stress/strain conditions related to plaque rupture which often leads directly to heart attack or stroke. An important modeling issue is how to determine zero stress state from in vivo plaque geometries. This paper presents a method to quantify human carotid artery axial and inner circumferential shrinkages by using patient-specific ex vivo and in vivo MRI images. A shrink-stretch process based on patient-specific in vivo plaque morphology and shrinkage data was introduced to shrink the in vivo geometry first to find the zero-stress state (opening angle was ignored to reduce the complexity), and then stretch and pressurize to recover the in vivo plaque geometry with computed initial stress, strain, flow pressure and velocity conditions. Effects of the shrink-stretch process on plaque stress/strain distributions were demonstrated based on patient-specific data using 3D models with fluid-structure interactions (FSI). The average artery axial and inner circumferential shrinkages were 25% and 7.9%, respectively, based on a data set obtained from 10 patients. Maximum values of maximum principal stress and strain increased 349.8% and 249% respectively with 33% axial stretch. Influence of inner circumferential shrinkage (7.9%) was not very noticeable under 33% axial stretch, but became more noticeable under smaller axial stretch. Our results indicated that accurate knowledge of artery shrinkages and the shrink-stretch process will considerably improve the accuracy of computational predictions made based on results from those in vivo MRI-based FSI models.     

Mechanical behavior of human aortas: Experiments,material constants and 3-D finite element modeling including residual stress

Segments of fresh human ascending, thoracic descending and abdominal aortas from eight male sexagenarians were pressurized under closed-end and free extension conditions. The median unpressurized inner radii for the ascending, thoracic and abdominal locations were 14.21, 9.67 and 7.16 mm, respectively. The median thickness was similar in the ascending and thoracic regions, at about 1.6 mm, while it was 1.2 mm in the abdominal region. The opening angle was not statistically different between regions, with a median of ?38°. Under 13.3 kPa pressure, the median circumferential stretch ratio was about 1.26 in all three aortic locations; the median longitudinal stretch ratio was similar in the ascending and thoracic regions, at about 1.13, while it was 1.05 in the abdominal region. Material constants for a three-dimensional hyperelastic anisotropic constitutive model were determined. Experimental, analytical and finite element results showed excellent agreement, validating the novel experimental approach and the numerical methods used. When residual stress was not taken into account, stresses were highest on the inside of the aorta, with a gradient across the wall of about 200 and 50 kPa in the circumferential and longitudinal directions, respectively. When residual stress was included as described by negative opening angles, stresses were highest on the outside of the aorta, with a gradient across the wall in excess of 400 kPa for the circumferential direction, and on the order of 150 kPa for the longitudinal direction. The mechanical consequences of negative opening angles had not been appreciated so far, and deserve further investigation.     

Shear modulus of porcine coronary artery: contributions of media and adventitia

The epicardial coronary arteries experience significant torsion in the axial direction due to changes in the shape of the heart during the cardiac cycle. The objective of this study was to determine the torsional mechanical properties of the coronary arteries under various circumferential and longitudinal loadings. The coronary artery was treated as a two-layer composite vessel consisting of intima-medial and adventitial layers, and the shear modulus of each layer was determined. Eight porcine hearts were obtained at a local abattoir, and their right coronary and left anterior descending arteries were isolated and tested in vitro with a triaxial torsion machine (inflation, longitudinal stretch, and circumferential twist). After the intact vessel was tested, the adventitia was dissected away, leaving an intact media that was then tested under identical triaxial loading conditions. We proposed a biomechanical analysis to compute the shear modulus of the adventitia from the measured shear moduli of the intact vessel and the media. To validate our predictions, we used four additional hearts in which the shear modulus of the adventitia was measured after dissection of media. Our results show that the shear modulus does not depend on the shear stress or strain but varies linearly with circumferential and longitudinal stresses and in a nonlinear way with the corresponding strains. Furthermore, we found that the shear modulus of the adventitia is larger than that of the intact vessel, which is larger than the vessel media. These results may have important implications for baroreceptor sensitivity, circulation of the vasa vasorum, and coronary dissection.     

A model for passive elastic properties of rat vena cava

A two-dimensional model for the elastic properties of vena cava abdominalis under orthotropic deformation is introduced and tested against the experimental data obtained from six specimen of rat venae cavae by pressurization experiments. The model is based on membrane approximation and suited for vessels where most of the elastic elements are oriented axially, while circumferential contraction is exerted by redirecting axial stress by some network of oblique fibers. For the experimental data considered in this paper, the ratio between axial and circumferential stress depends almost exclusively on the circumferential extension ratio. As a consequence, the mechanical system can be formally decomposed in a kinematic system reacting by axial contraction on circumferential extension without any loss or storage of energy, serially connected to a hyperelastic system acting only in axial direction. Both systems are modeled separately by equations obtained by a purely phenomenological approach with two parameters for each system. This leads to reasonable reproduction of the experimental data. Introducing a correction parameter, which takes into account that the model assumption on the decomposition does not hold exactly, we get better reproduction of data. However, this is paid for by loss of physical rigor and in particular by departing from the assumption of hyperelasticity.     

Diameter-dependent axial prestretch of porcine coronary arteries and veins

The pressure-diameter relation (PDR) and the wall strain of coronary blood vessels have important implications for coronary blood flow and arthrosclerosis, respectively. Previous studies have shown that these mechanical quantities are significantly affected by the axial stretch of the vessels. The objective of this study was to measure the physiological axial stretch in the coronary vasculature; i.e., from left anterior descending (LAD) artery tree to coronary sinus vein and to determine its effect on the PDR and hence wall stiffness. Silicone elastomer was perfused through the LAD artery and coronary sinus trees to cast the vessels at the physiologic pressure. The results show that the physiological axial stretch exists for orders 4 to 11 (> 24 μm in diameter) arteries and orders -4 to -12 (>38 μm in diameter) veins but vanishes for the smaller vessels. Statistically, the axial stretch is higher for larger vessels and is higher for arteries than veins. The axial stretch λ(z) shows a linear variation with the order number (n) as: λ(z) = 0.062n + 0.75 (R(2) = 0.99) for artery and λ(z) = -0.029n + 0.89 (R(2) = 0.99) for vein. The mechanical analysis shows that the axial stretch significantly affects the PDR of the larger vessels. The circumferential stretch/strain was found to be significantly higher for the epicardial arteries (orders 9-11), which are free of myocardium constraint, than the intramyocardial arteries (orders 4-8). These findings have fundamental implications for coronary blood vessel mechanics.     

A comparison of uniaxial and biaxial mechanical properties of the annulus fibrosus: a porcine model

The annulus fibrosus of the intervertebral disk experiences multidirectional tension in vivo, yet the majority of mechanical property testing has been uniaxial. Therefore, our understanding of how this complex multilayered tissue responds to loading may be deficient. This study aimed to determine the mechanical properties of porcine annular samples under uniaxial and biaxial tensile loading. Two-layer annulus samples were isolated from porcine disks from four locations: anterior superficial, anterior deep, posterior superficial, and posterior deep. These tissues were then subjected to three deformation conditions each to a maximal stretch ratio of 1.23: uniaxial, constrained uniaxial, and biaxial. Uniaxial deformation was applied in the circumferential direction, while biaxial deformation was applied simultaneously in the circumferential and compressive directions. Constrained uniaxial consisted of a stretch ratio of 1.23 in the circumferential direction while holding the tissue stationary in the axial direction. The maximal stress and stress-stretch ratio (S-S) moduli determined from the biaxial tests were significantly higher than those observed during both the uniaxial tests (maximal stress, 97.1% higher during biaxial; p=0.002; S-S moduli, 117.9% higher during biaxial; p=0.0004) and the constrained uniaxial tests (maximal stress, 46.8% higher during biaxial; S-S moduli, 82.9% higher during biaxial). These findings suggest that the annulus is subjected to higher stresses in vivo when under multidirectional tension.     

Morphologic adaptation of arterial endothelial cells to longitudinal stretch in organ culture

Arteries in vivo are subjected to large longitudinal stretch, which changes significantly due to vascular disease and surgery. However, little is known about the effect of longitudinal stretch on arterial endothelium. The aim of this study was to determine the morphologic adaptation of arterial endothelial cells (ECs) to elevated axial stretch. Porcine carotid arteries were stretched 20% more than their in vivo length while being maintained at physiological pressure and flow rate in an organ culture system. The ECs were elongated with the application of the axial stretch (aspect ratio 2.81+/-0.25 versus 3.65+/-0.38, n=8, p<0.001). The elongation was slightly decreased after three days and the ECs recovered their normal shape after seven days, as measured by the shape index and aspect ratio (0.55+/-0.03 versus 0.56+/-0.04, and 2.93+/-0.28 versus 2.88+/-0.20, respectively, n=5). Cell proliferation was increased in the intima of stretched arteries in three days as compared to control arteries but showed no difference after seven days in organ culture. These results demonstrate that the ECs adapt to axial stretch and maintain their normal shape.     

The effect of the elongation of the proximal aorta on the estimation of the aortic wall distensibility

The compliance of the proximal aortic wall is a major determinant of cardiac afterload. Aortic compliance is often estimated based on cross-sectional area changes over the pulse pressure, under the assumption of a negligible longitudinal stretch during the pulse. However, the proximal aorta is subjected to significant axial stretch during cardiac contraction. In the present study, we sought to evaluate the importance of axial stretch on compliance estimation by undertaking both an in silico and an in vivo approach. In the computational analysis, we developed a 3-D finite element model of the proximal aorta and investigated the discrepancy between the actual wall compliance to the value estimated after neglecting the longitudinal stretch of the aorta. A parameter sensitivity analysis was further conducted to show how increased material stiffness and increased aortic root motion might amplify the estimation errors (discrepancies between actual and estimated distensibility ranging from − 20 to − 62%). Axial and circumferential aortic deformation during ventricular contraction was also evaluated in vivo based on MR images of the aorta of 3 healthy young volunteers. The in vivo results were in good qualitative agreement with the computational analysis (underestimation errors ranging from − 26 to − 44%, with increased errors reflecting higher aortic root displacement). Both the in silico and in vivo findings suggest that neglecting the longitudinal strain during contraction might lead to severe underestimation of local aortic compliance, particularly in the case of women who tend to have higher aortic root motion or in subjects with stiff aortas.

     

Mechanical anisotropy of inflated elastic tissue from the pig aorta

Uniaxial and biaxial mechanical properties of purified elastic tissue from the proximal thoracic aorta were studied to understand physiological load distributions within the arterial wall. Stress–strain behaviour was non-linear in uniaxial and inflation tests. Elastic tissue was 40% stiffer in the circumferential direction compared to axial in uniaxial tests and～100% stiffer in vessels at an axial stretch ratio of 1.2 or 1.3 and inflated to physiological pressure. Poisson’s ratio v_θz averaged 0.2 and v_zθ increased with circumferential stretch from ～0.2 to ～0.4. Axial stretch had little impact on circumferential behaviour. In intact (unpurified) vessels at constant length, axial forces decreased with pressure at low axial stretches but remained constant at higher stretches. Such a constant axial force is characteristic of incrementally isotropic arteries at their in vivo dimensions. In purified elastic tissue, force decreased with pressure at all axial strains, showing no trend towards isotropy. Analysis of the force–length–pressure data indicated a vessel with v_θz≈0.2 would stretch axially 2–4% with the cardiac pulse yet maintain constant axial force. We compared the ability of 4 mathematical models to predict the pressure-circumferential stretch behaviour of tethered, purified elastic tissue. Models that assumed isotropy could not predict the stretch at zero pressure. The neo-Hookean model overestimated the non-linearity of the response and two non-linear models underestimated it. A model incorporating contributions from orthogonal fibres captured the non-linearity but not the zero-pressure response. Models incorporating anisotropy and non-linearity should better predict the mechanical behaviour of elastic tissue of the proximal thoracic aorta.     

Three-dimensional stress and strain distribution in a two-layer model of a coronary artery

For a right coronary artery, three-dimensional stress and strain distributions at a physiological intraluminal pressure and an axial extension ratio were computed on the basis of a two-layer elastic model. To validate the model, curves of external radius versus pressure and of axial force versus pressure were computed for three axial extension ratios. To analyze mechanical properties, stress-free configurations of media and adventitia, and the constitutive law of each layer in literature, were used. The present study showed that the peak circumferential stress and the peak axial stress appear in the media at the boundary between the media and adventitia. This result is due to the opening angle of the media being larger than π (rad) and the larger value of a material constant of the strain energy function for the media than for the adventitia. The circumferential stress and strain were discontinuous at the boundary. On the other hand, the radial stress was continuous at the boundary because of the boundary condition for stress. The circumferential stress and axial stress in the adventitia were almost uniformly distributed, and smaller than in the media. The residual stress and strain were also computed. The circumferential residual stress and strain were almost linearly distributed in each layer, although discontinuity appeared at the boundary between the two layers.     

Pipette aspiration technique for the measurement of nonlinear and anisotropic mechanical properties of blood vessel walls under biaxial stretch

A pipette aspiration technique was proposed for the measurement of nonlinear mechanical properties of arteries under biaxial stretching. A cross-shaped specimen of porcine thoracic aorta whose principal axes corresponded with the axial and circumferential directions of the aortic walls was excised. The intraluminal surface of the specimen was aspirated with a circular cross-sectioned glass pipette while the specimen was stretching in the axial and circumferential directions in 10% increments. The elastic modulus agreed with the incremental elastic modulus obtained through a conventional pressure-diameter test of the same specimen to within an error of 30% at a circumferential stretch ratio below 1.3 and an axial stretch ratio of 1.0, 1.1 or 1.2, which represent lower range of physiological stretch ratios for the porcine aorta. A rectangular cross-sectioned pipette was utilized to measure anisotropic properties of the specimen under biaxial stretching. When aspirated with such a pipette, the specimens' elastic properties along the length of the rectangular pipette cross section can be neglected. The elastic modulus was found to increase rapidly when the specimen was stretched in the direction of the pipette's width. Thus, pipette aspiration should have many advantages such as well measurement of the local nonlinear and anisotropic mechanical properties of blood vessel walls.     

Flow-induced shear strain in intima of porcine coronary arteries.

The in vivo circumferential strain has a small variation throughout the vascular system (aorta to arterioles). The axial strain has also been shown to be nearly the same as the circumferential strain under physiological loading. Since the endothelium is mechanically much softer than the media-adventitia in healthy arteries, the porcine intima was considered as a mechanically distinct layer from the media-adventitia in a two-layer computational model. Based on the simulation result, we hypothesize that the flow-induced shear strain in intima can be of similar value as the pressure-induced circumferential strain in healthy coronary arteries, even though the shear stress is orders of magnitude smaller than the circumferential stress. The nearly isotropic deformation (circumferential, axial, and shear strains) may have important implications for mechanical homeostasis of endothelial cells, mechanotransduction, growth, and remodeling of blood vessels.     

Effect of cyclic axial stretch of rat arteries on endothelial cytoskeletal morphology and vascular reactivity

Pulsatile fluid shear stress and circumferential stretch are responsible for the axial alignment of vascular endothelial cells and their actin stress fibers in vivo. We studied the effect of cyclic alterations in axial stretch independent of flow on endothelial cytoskeletal organization in intact arteries and determined if functional alterations accompanied morphologic alterations. Rat renal arteries were axially stretched (20%, 0.5 Hz) around their in vivo lengths, for up to 4h. Actin stress fibers were examined by immunofluorescent staining. We found that cyclic axial stretching of intact vessels under normal transmural pressure in the absence of shear stress induces within a few hours realignment of endothelial actin stress fibers toward the circumferential direction. Concomitant with this morphologic alteration, the sensitivity (log(EC(50))) to the endothelium-dependent vasodilator (acetylcholine) was significantly decreased in the stretched vessels (after stretching -5.15+/-0.79 and before stretching -6.71+/-0.78, resp.), while there was no difference in sodium nitroprusside (SNP) sensitivity. There was no difference in sensitivity to both acetylcholine and SNP in time control vessels. Similar to cultured cells, endothelial cells in intact vessels subjected to cyclic stretching reorganize their actin filaments almost perpendicular to the stretching direction. Accompanying this morphological alteration is a loss of endothelium-dependent vasodilation but not of smooth muscle responsiveness.     

Linked mechanical and biological aspects of remodeling in mouse pulmonary arteries with hypoxia-induced hypertension

Supravalvular aortic stenosis (SVAS) is associated with decreased elastin and altered arterial mechanics. Mice with a single deletion in the elastin gene (ELN(+/-)) are models for SVAS. Previous studies have shown that elastin haploinsufficiency in these mice causes hypertension, decreased arterial compliance, and changes in arterial wall structure. Despite these differences, ELN(+/-) mice have a normal life span, suggesting that the arteries remodel and adapt to the decreased amount of elastin. To test this hypothesis, we performed in vitro mechanical tests on abdominal aorta, ascending aorta, and left common carotid artery from ELN(+/-) and wild-type (C57BL/6J) mice. We compared the circumferential and longitudinal stress-stretch relationships and residual strains. The circumferential stress-stretch relationship is similar between genotypes and changes <3% with longitudinal stretch at lengths within 10% of the in vivo value. At mean arterial pressure, the circumferential stress in the ascending aorta is higher in ELN(+/-) than in wild type. Although arterial pressures are higher, the increased number of elastic lamellae in ELN(+/-) arteries results in similar tension/lamellae compared with wild type. The longitudinal stress-stretch relationship is similar between genotypes for most arteries. Compared with wild type, the in vivo longitudinal stretch is lower in ELN(+/-) abdominal and carotid arteries and the circumferential residual strain is higher in ELN(+/-) ascending aorta. The increased circumferential residual strain brings the transmural strain distribution in ELN(+/-) ascending aorta close to wild-type values. The mechanical behavior of ELN(+/-) arteries is likely due to the reduced elastin content combined with adaptive remodeling during vascular development.     

Contribution of elastin and collagen to the inflation response of the pig thoracic aorta: assessing elastin's role in mechanical homeostasis

This study was undertaken to understand elastin's role in the mechanical homeostasis of the arterial wall. The mechanical properties of elastin vary along the aorta, and we hypothesized this maintained a uniform mechanical environment for the elastin, despite regional variation in loading. Elastin's physiological loading was determined by comparing the inflation response of intact and autoclave purified elastin aortas from the proximal and distal thoracic aorta. Elastin's stretch and stress depend on collagen recruitment. Collagen recruitment started in the proximal aorta at systolic pressures (13.3 to 14.6 kPa) and in the distal at sub-diastolic pressures (9.3 to 10.6 kPa). In the proximal aorta collagen did not contribute significantly to the stress or stiffness, indicating that elastin determined the vessel properties. In the distal aorta, the circumferential incremental modulus was 70% higher than in the proximal aorta, half of which (37%) was due to a stiffening of the elastin. Compared to the elastin tissue in the proximal aorta, the distal elastin suffered higher physiological circumferential stretch (29%, P=0.03), circumferential stress (39%, P=0.02), and circumferential stiffness (37%, P=0.006). Elastin's physiological axial stresses were also higher (67%, P=0.003). These findings do not support the hypothesis that the loading on elastin is constant along the aorta as we expected from homeostasis.