Mechanical testing and constitutive modelling of isolated arterial layers yields insight into the individual layers’ mechanical properties, but per se fails to recapitulate the in vivo loading state, neglecting layer-specific residual stresses. The aim of this study was to develop a testing/modelling framework that integrates layer-specific uniaxial testing data into a three-layered model of the arterial wall, thereby enabling study of layer-specific mechanics under realistic (patho)physiological conditions. Circumferentially and axially oriented strips of pig thoracic aortas (n = 10) were tested uniaxially. Individual arterial layers were then isolated from the wall, tested, and their mechanical behaviour modelled using a hyperelastic strain energy function. Subsequently, the three layers were computationally assembled into a single flat-walled sample, deformed into a cylindrical vessel, and subjected to physiological tension-inflation. At the in vivo axial stretch of 1.10 ± 0.03, average circumferential wall stress was 75 ± 9 kPa at 100 mmHg, which almost doubled to 138 ± 15 kPa at 160 mmHg. A ~ 200% stiffening of the adventitia over the 60 mmHg pressure increase shifted layer-specific load-bearing from the media (65 ± 10% → 61 ± 14%) to the adventitia (28 ± 9% → 32 ± 14%). Our approach provides valuable insight into the (patho)physiological mechanical roles of individual arterial layers at different loading states, and can be implemented conveniently using simple, inexpensive and widely available uniaxial testing equipment.

The arterial wall is characterised by a complex microstructure that impacts the mechanical properties of the vascular tissue. The main components consist of collagen and elastin fibres, proteoglycans, Vascular Smooth Muscle Cells (VSMCs) and ground matrix. While VSMCs play a key role in the active mechanical response of arteries, collagen and elastin determine the passive mechanics. Several experimental methods have been designed to investigate the role of these structural proteins in determining the passive mechanics of the arterial wall. Microscopy imaging of load-free or fixed samples provides useful information on the structure-function coupling of the vascular tissue, and mechanical testing provides information on the mechanical role of collagen and elastin networks. However, when these techniques are used separately, they fail to provide a full picture of the arterial micromechanics. More recently, advances in imaging techniques have allowed combining both methods, thus dynamically imaging the sample while loaded in a pseudo-physiological way, and overcoming the limitation of using either of the two methods separately. The present review aims at describing the techniques currently available to researchers for the investigation of the arterial wall micromechanics. This review also aims to elucidate the current understanding of arterial mechanics and identify some research gaps.

Pulse wave velocity, a common metric of arterial stiffness, is an established predictor for cardiovascular events and mortality. However, its intrinsic pressure-dependency complicates the discrimination of acute and chronic impacts of increased blood pressure on arterial stiffness. Cardio-ankle vascular index (CAVI) represented a significant step towards the development of a pressure-independent arterial stiffness metric. However, some potential limitations of CAVI might render this arterial stiffness metric less pressure-independent than originally thought. For this reason, we later introduced CAVI0. Nevertheless, advantages of one approach over the other are left debated. This review aims to shed light on the pressure (in)dependency of both CAVI and CAVI0. By critically reviewing results from studies reporting both CAVI and CAVI0 and using simple analytical methods, we show that CAVI0 may enhance the pressure-independent assessment of arterial stiffness, especially in the presence of large inter-individual differences in blood pressure.

The existence of residual stresses in unloaded arteries has long been known. However, their effect is often neglected in experimental studies. Using a recently developed modelling framework, we aimed to investigate the role of residual stresses in the mechanical behaviour of the tri-layered wall of the pig thoracic aorta. The mechanical behaviour of the intact wall and isolated layers of n = 3 pig thoracic aortas was investigated via uniaxial tensile testing. After modelling the layer-specific mechanical data using a hyperelastic strain energy function, the layer-specific deformations in the unloaded vessel were estimated so that the mechanical response of the computationally assembled tri-layered flat wall would match that measured experimentally. Physiological tension–inflation of the cylindrical tri-layered vessel was then simulated, analysing changes in the distribution of stresses in the three layers when neglecting residual stresses. In the tri-layered model with residual stresses, layers exhibited comparable stresses throughout the physiological range of pressure. At 100 mmHg, intimal, medial, and adventitial circumferential load bearings were 16 $$\pm$$ ±  3%, 59 $$\pm$$ ± 4%, and 25 $$\pm$$ ± 2%, respectively. Adventitial stiffening at high pressures produced a shift in load bearing from the media to the adventitia. When neglecting residual stresses, in vivo stresses were highest at the intima and lowest at the adventitia. Consequently, the intimal and adventitial load bearings, 23 $$\pm$$ ± 2% and 18 $$\pm$$ ± 3% at 100 mmHg, were comparable at all pressures. Residual stresses play a crucial role in arterial mechanics guaranteeing a uniform distribution of stresses through the wall thickness. Neglecting these leads to incorrect interpretation of the layers’ role in arterial mechanics.