Payman Jalali

The transport of LDL across the deformable arterial wall: the effect of endothelial cell turnover and intimal deformation under hypertension

A multilayered model of the aortic wall is introduced to investigate the transport of low-density lipoprotein (LDL) under hypertension, taking into account the influences of increased endothelial cell turnover and deformation of the intima at higher pressure. Meanwhile, the thickness and properties of the endothelium, intima, internal elastic lamina (IEL), and media are affected by the transmural pressure. The LDL macromolecules enter the intima through leaky junctions over the endothelium, which are created by dying or dividing cells. Water molecules enter the intima via the paracellular pathway through breaks in tight junctions after passing the glycocalyx as well as through leaky junctions. The glycocalyx is modeled as a Brinkman porous medium to describe the fluid filtration associated with its structure. Combined Navier-Stokes and Brinkman equations are solved for the transmural flow, and the convective-diffusion equation is employed for LDL transport. The permeation of LDL over the surface of smooth muscle cells is modeled through a uniform reaction evenly distributed in the macroscopically homogeneous media layer. Simulations are performed in an axisymmetric plane centered at a leaky cell. The overriding issue addressed is that LDL fluxes across the leaky junction, the intima, fenestral pores in the IEL, and the media layer are highly affected by the transmural pressure, which affects the endothelial cell turnover rate and the compaction of intima. The present model, for the first time and with no adjustable parameters, is capable of making many realistic predictions including the proper magnitudes for the permeability of endothelium and intimal layers and the hydraulic conductivity of all layers as well as their trends with pressure. Results for the volume flux through the wall and the hydraulic conductivity of the entire arterial wall, the endothelium, and subendothelial layers at 70 and 180 mmHg are in good agreement with previous experimental studies.

Finite element modelling of pulsatile blood flow in idealized model of human aortic arch: study of hypotension and hypertension.

A three-dimensional computer model of human aortic arch with three branches is reproduced to study the pulsatile blood flow with Finite Element Method. In specific, the focus is on variation of wall shear stress, which plays an important role in the localization and development of atherosclerotic plaques. Pulsatile pressure pulse is used as boundary condition to avoid flow entry development, and the aorta walls are considered rigid. The aorta model along with boundary conditions is altered to study the effect of hypotension and hypertension. The results illustrated low and fluctuating shear stress at outer and inner wall of aortic arch, proximal wall of branches, and entry region. Despite the simplification of aorta model, rigid walls and other assumptions results displayed that hypertension causes lowered local wall shear stresses. It is the sign of an increased risk of atherosclerosis. The assessment of hemodynamics shows that under the flow regimes of hypotension and hypertension, the risk of atherosclerosis localization in human aorta may increase.

Particle interactions in a dense monosized granular flow

Abstract Simulations of bounded dense sheared granular flows were performed to investigate multi-phase flow phenomena, in particular the behavior of the ordered phase. In the absence of gravity, collapse of the granular structures was found to occur for a wide range of shear rate, as evidenced by the disappearance of the signature of the ordered structure in the wall normal stress signal. However, normal stress signals matching those detected in recent experiments were obtained for a system whose dynamics were collision-dominated rather than friction-dominated. Moreover, the system was found to exhibit a similar flow behavior in the presence of gravity. The stress signals were analyzed using wavelet transforms, which indicated the existence of stick–slip dynamics, characterized by harmonic frequencies. It is shown that these observations might elucidate the origin of stick–slip dynamics in the system, which experienced instability due to gravitational compactification at shear rates below a certain critical value.

Intermittency of energy in rapid granular shear flows

Hard-disk simulations are used for two-dimensional rapid granular shear flows of circular disks between two rotating cylinders. The intermittency effects associated with the rate of the energy dissipation of collisions are studied. The statistics of intermittent signals of energy dissipation reveals that a power law governs the dynamics of rapid shear granular flows. A dynamical system approach based on the Gledzer-Ohkitani-Yamada shell model of turbulence is employed to reproduce signals for energy dissipation that are statistically consistent with those from simulations. The results suggest that rapid granular flows can be analyzed by appropriate turbulent models.

Shear-induced force transmission in a multicomponent, multicell model of the endothelium

Haemodynamic forces applied at the apical surface of vascular endothelial cells (ECs) provide the mechanical signals at intracellular organelles and through the inter-connected cellular network. The objective of this study is to quantify the intracellular and intercellular stresses in a confluent vascular EC monolayer. A novel three-dimensional, multiscale and multicomponent model of focally adhered ECs is developed to account for the role of potential mechanosensors (glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs) and adherens junctions (ADJs)) in mechanotransmission and EC deformation. The overriding issue addressed is the stress amplification in these regions, which may play a role in subcellular localization of mechanotransmission. The model predicts that the stresses are amplified 250–600-fold over apical values at ADJs and 175–200-fold at FAs for ECs exposed to a mean shear stress of 10 dyne cm−2. Estimates of forces per molecule in the cell attachment points to the external cellular matrix and cell–cell adhesion points are of the order of 8 pN at FAs and as high as 3 pN at ADJs, suggesting that direct force-induced mechanotransmission by single molecules is possible in both. The maximum deformation of an EC in the monolayer is calculated as 400 nm in response to a mean shear stress of 1 Pa applied over the EC surface which is in accord with measurements. The model also predicts that the magnitude of the cell–cell junction inclination angle is independent of the cytoskeleton and glycocalyx. The inclination angle of the cell–cell junction is calculated to be 6.6° in an EC monolayer, which is somewhat below the measured value (9.9°) reported previously for ECs subjected to 1.6 Pa shear stress for 30 min. The present model is able, for the first time, to cross the boundaries between different length scales in order to provide a global view of potential locations of mechanotransmission.

The study of wall deformation and flow distribution with transmural pressure by three-dimensional model of thoracic aorta wall

The sensitivity of shear stress over smooth muscle cells (SMCs) to the deformability of media layer due to pressure is investigated in thoracic aorta wall using three-dimensional simulations. A biphasic, anisotropic model assuming the radius, thickness, and hydraulic conductivity of vessel wall as functions of transmural pressure is employed in numerical simulations. The leakage of interstitial fluid from intima to media layer is only possible through fenestral pores on the internal elastic lamina (IEL). The media layer is assumed a heterogeneous medium containing SMCs embedded in a porous extracellular matrix of elastin, proteoglycan, and collagen fibers. The applicable pressures for the deformation of media layer are varied from 0 to 180 mmHg. The SMCs are cylindrical objects of circular cross section at zero pressure. The cross sectional shape of SMCs changes from circle to ellipse as the media is compressed. The local shear stress over the nearest SMC to the IEL profoundly depends on pressure, SMCs configurations, and the corresponding distance to the IEL. The consideration of various SMC configurations, namely the staggered and square arrays, mimics various physiological conditions that can happen in positioning of an SMC. The results of our simulations show that even the second nearest SMCs to the IEL can significantly change their functions due to high shear stress levels. This is in contrast to earlier studies suggesting the highest vulnerability to shear stress for the innermost layer of SMCs at the intimal-medial interface.

Effect of the shape and configuration of smooth muscle cells on the diffusion of ATP through the arterial wall

In this study, the shape and the configuration of smooth muscle cells (SMCs) within the arterial wall are altered to investigate their influence on molecular transport across the media layer of the thoracic aorta wall. In a 2D geometry of the media layer containing SMCs, the finite-element method has been employed to simulate the diffusion of solutes through the media layer. The media is modeled as a heterogeneous system composed of SMCs having elliptic or circular cross sections embedded in a homogeneous porous medium made of proteoglycan and collagen fibers with an interstitial fluid filling the void. The arrangement of SMCs is in either ordered or disordered fashion for different volume fractions of SMCs. The interstitial fluid enters the media through fenestral pores, which are assumed to be distributed uniformly over the internal elastic lamina (IEL). Results revealed that in an ordered arrangement of SMCs, the concentration of adenosine 5′-triphosphate (ATP) over the surface of SMCs with an elliptic cross section is 5–8% more than those of circular SMCs in volume fractions of 0.4–0.7. The ATP concentration at the SMC surface decreases with volume fraction in the ordered configuration of SMCs. In a disordered configuration, the local ATP concentration at the SMC surface and in the bulk are strongly dependent on the distance between neighboring SMCs, as well as the minimum distance between SMCs and fenestral pores. Moreover, the SMCs in farther distances from the IEL are as important as those just beneath the IEL in disordered configurations. The results of this study lead us to better understanding of the role of SMCs in controlling the diffusion of important species such as ATP within the arterial wall.

Self-diffusion in unbounded rapid granular flows: a nonequilibrium approach

Using a nonequilibrium simulation scheme, the transverse diffusive motion has been investigated in unbounded shear flows of smooth, monodisperse, inelastic spherical particles. This scheme is used to obtain the concentration gradient due to the particle mass flux, which is extracted from the bulk flow using a certain labeling algorithm. The self-diffusion coefficient can then be obtained from Ficks law. Under steady conditions, the simulation results show that the particle diffusivity can be described by a linear law. This finding provides a justification for assuming a linear law relationship in the kinetic theory type derivation of an expression for self-diffusivity. Moreover, the values of self-diffusion coefficient from the computer simulations agree with those obtained using kinetic theory formulations for solid volume fractions less than 0.5.

Hemodynamic Features in Stenosed Coronary Arteries: CFD Analysis Based on Histological Images

Histological images from the longitudinal section of four diseased coronary arteries were used, for the first time, to study the pulsatile blood flow distribution within the lumen of the arteries by means of computational fluid dynamics (CFD). Results indicate a strong dependence of the hemodynamics on the morphology of atherosclerotic lesion. Distinctive flow patterns appear in different stenosed regions corresponding to the specific geometry of any artery. Results show that the stenosis affects the wall shear stress (WSS) locally along the diseased arterial wall as well as other adjacent walls. The maximum magnitude of WSS is observed in the throat of stenosis. Moreover, high oscillatory shear index (OSI) is observed along the stenosed wall and the high curvature regions. The present study is capable of providing information on the shear environment in the longitudinal section of the diseased coronary arteries, based on the models created from histological images. The computational method may be used as an effective way to predict plaque forming regions in healthy arterial walls.

Tissue prolapse and stresses in stented coronary arteries

Among the many factors influencing the effectiveness of cardiovascular stents, tissue prolapse indicates the potential of a stent to cause restenosis. The deflection of the arterial wall between the struts of the stent and the tissue is known as a prolapse or draping. The prolapse is associated with injury and damage to the vessel wall due to the high stresses generated around the stent when it expands. The current study investigates the impact of stenosis severity and plaque morphology on prolapse in stented coronary arteries. A finite element method is applied for the stent, plaque, and artery set to quantify the tissue prolapse and the corresponding stresses in stenosed coronary arteries. The variable size of atherosclerotic plaques is considered. A plaque is modelled as a multi-layered medium with different thicknesses attached to the single layer of an arterial wall. The results reveal that the tissue prolapse is influenced by the degree of stenosis severity and the thickness of the plaque layers. Stresses are observed to be significantly different between the plaque layers and the arterial wall tissue. Higher stresses are concentrated in fibrosis layer of the plaque (the harder core), while lower stresses are observed in necrotic core (the softer core) and the arterial wall layer. Moreover, the morphology of the plaque regulates the magnitude and distribution of the stress. The fibrous cap between the necrotic core and the endothelium constitutes the most influential layer to alter the stresses. In addition, the thickness of the necrotic core and the stenosis severity affect the stresses. This study reveals that the morphology of atherosclerotic plaques needs to be considered a key parameter in designing coronary stents.