Low-density Lipoprotein Transport Research Articles

Sphingosine-1-phosphate receptor 3 regulates the transendothelial transport of high-density lipoproteins and low-density lipoproteins in opposite ways.

The entry of lipoproteins from blood into the arterial wall is a rate-limiting step in atherosclerosis. It is controversial whether this happens by filtration or regulated transendothelial transport.Because sphingosine-1-phosphate (S1P) preserves the endothelial barrier, we investigated in vivo and in vitro, whether S1P and its cognate S1P-receptor 3 (S1P3) regulate the transendothelial transport of lipoproteins. Compared to apoE-haploinsufficient mice (CTRL), apoE-haploinsufficient mice with additional endothelium-specific knock-in of S1P3 (S1P3-iECKI) showed decreased transport of LDL and Evan's Blue but increased transport of HDL from blood into the peritoneal cave. After 30 weeks of high-fat diet feeding, S1P3-iECKI mice had lower levels of non-HDL-cholesterol and less atherosclerosis than CTRL mice. In vitro stimulation with an S1P3 agonist increased the transport of 125I-HDL but decreased the transport of 125I-LDL through human aortic endothelial cells (HAECs). Conversely, inhibition or knock-down of S1P3 decreased the transport of 125I-HDL but increased the transport of 125I-LDL. Silencing of SCARB1 encoding scavenger receptor B1 (SR-BI) abrogated the stimulation of 125I-HDL transport by the S1P3 agonist. The transendothelial transport of 125I-LDL was decreased by silencing of SCARB1 or ACVLR1 encoding activin-like kinase 1 but not by interference with LDLR. None of the three knock-downs prevented the stimulatory effect of S1P3 inhibition on transendothelial 125I-LDL transport. S1P3 regulates the transendothelial transport of HDL and LDL oppositely by SR-BI-dependent and SR-BI-independent mechanisms, respectively. This divergence supports a contention that lipoproteins pass the endothelial barrier by specifically regulated mechanisms rather than passive filtration.

The Influence of Adiponectin on Transport of Low-Density Lipoproteins through Human Endothelial Cell Monolayer In Vitro.

The influence of adiponectin, a protein secreted by adipocytes, on the activation of transendothelial LDL transport, the initial event of atherogenesis, was studied. The addition of adiponectin to the cultured endothelial hybridoma EA.hy926 cells did not affect both basal and TNF-stimulated transendothelial transport of LDL. In addition, adiponectin affects neither expression levels of CAV1, SCARB1, and ACVRL1 genes encoding proteins involved in transendothelial LDL transport, nor the MMP secretion by the EA.hy926cells. At the same time, adiponectin suppressed the TNF-stimulated IL-8 production and expression of the adhesion molecule gene ICAM1 in these cells. Thus, adiponectin reduces proinflammatory activation of EA.hy926 cells, which is not accompanied by changes in the transendothelial LDL transport. We speculate that anti-inflammatory action of adiponectin is the base for the influence of this adipokine on atherogenesis.

Inflammatory Cell-Derived MYDGF Attenuates Endothelial LDL Transcytosis to Protect Against Atherogenesis.

Inflammation contributes to the pathogenesis of atherosclerosis. But little is known about the potential benefits of inflammatory cells to atherosclerosis. The aim of this study was to investigate the function of inflammatory cells/endothelium axis and determine whether and how inflammatory cell-derived MYDGF (myeloid-derived growth factor) inhibited endothelial LDL (low-density lipoprotein) transcytosis. In in vivo experiments, both loss- and gain-of-function strategies were used to evaluate the effect of inflammatory cell-derived MYDGF on LDL transcytosis. We generated monocyte/macrophage-targeted MYDGF-null mice on an Ldlr (LDL receptor)-/- background in the loss-of-function strategy and restored the inflammatory cell-derived MYDGF by bone marrow transplantation and inflammatory cell-specific overexpression of MYDGF mice model in the gain-of-function strategy. In in vitro experiments, coculture experiments between primary mouse aortic endothelial cells and macrophages and mouse aortic endothelial cells supplemented with or without recombinant MYDGF were conducted. Inflammatory cell-derived MYDGF deficiency aggravated endothelial LDL transcytosis, drove LDL uptake by artery wall, and thus exacerbated atherosclerosis in vivo. Inflammatory cell-derived MYDGF restoration by bone marrow transplantation and inflammatory cell MYDGF overexpression alleviated LDL transport across the endothelium, prevented LDL accumulation in the subendothelial space, and subsequently ameliorated atherosclerosis in vivo. Furthermore, in the in vitro study, macrophages isolated from MYDGF+/+ mice and recombinant MYDGF attenuated LDL transcytosis and uptake in mouse aortic endothelial cells. Mechanistically, MYDGF inhibited MAP4K4 (mitogen-activated protein kinase kinase kinase kinase isoform 4) phosphorylation, enhanced activation of Akt (protein kinase B)-1, and diminished the FoxO (forkhead box O) 3a signaling cascade to exert protective effects of MYDGF on LDL transcytosis and atherosclerosis. The findings support a role for inflammatory cell-derived MYDGF served as a cross talk factor between inflammatory cells and endothelial cells that inhibits LDL transcytosis across endothelium. MYDGF may become a novel therapeutic drug for atherosclerosis, and the beneficial effects of inflammatory cell in atherosclerosis deserve further attention.

Computational modeling of low-density lipoprotein accumulation at the carotid artery bifurcation after stenting.

Restenosis typically occurs in regions of low and oscillating wall shear stress, which also favor the accumulation of atherogenic macromolecules such as low-density lipoprotein (LDL). This study aims to evaluate LDL transport and accumulation at the carotid artery bifurcation following carotid artery stenting (CAS) by means of computational simulation. The computational model consists of coupled blood flow and LDL transport, with the latter being modeled as a dilute substance dissolved in the blood and transported by the flow through a convection-diffusion transport equation. The endothelial layer was assumed to be permeable to LDL, and the hydraulic conductivity of LDL was shear-dependent. Anatomically realistic geometric models of the carotid bifurcation were built based on pre- and post-stent computed tomography (CT) scans. The influence of stent design was investigated by virtually deploying two different types of stents (open- and closed-cell stents) into the same carotid bifurcation model. Predicted LDL concentrations were compared between the post-stent carotid models and the relatively normal contralateral model reconstructed from patient-specific CT images. Our results show elevated LDL concentration in the distal section of the stent in all post-stent models, where LDL concentration is 20 times higher than that in the contralateral carotid. Compared with the open-cell stents, the closed-cell stents have larger areas exposed to high LDL concentration, suggesting an increased risk of stent restenosis. This computational approach is readily applicable to multiple patient studies and, once fully validated against follow-up data, it can help elucidate the role of stent strut design in the development of in-stent restenosis after CAS.

Divergence of the normalized wall shear stress as an effective computational template of low-density lipoprotein polarization at the arterial blood-vessel wall interface

Background and ObjectiveNear-wall transport of low-density lipoproteins (LDL) in arteries plays a relevant role in the initiation of atherosclerosis. Although it can be modelled in silico by coupling the Navier–Stokes equations with the 3D advection-diffusion (AD) equation, the associated computational cost is high. As wall shear stress (WSS) represents a first-order approximation of the near-wall velocity in arteries, we aimed at identifying computationally convenient WSS-based quantities to infer LDL near-wall transport based on the underlying near-wall hemodynamics in five models of three human arterial districts (aorta, carotid bifurcations, coronary arteries). The simulated LDL transport and its WSS-based surrogates were qualitatively compared with in vivo longitudinal measurements of wall thickness growth on the coronary artery models. MethodsNumerical simulations of blood flow coupled with AD equations for LDL transport and blood-wall transfer were performed. The co-localization of the simulated LDL concentration polarization patterns with luminal surface areas characterized by low cycle-average WSS, near-wall flow stagnation and WSS attracting patterns was quantitatively assessed by the similarity index (SI). In detail, the latter two represent features of the WSS topological skeleton, obtained respectively through the Lagrangian tracking of surface-born particles, and the Eulerian analysis of the divergence of the normalized cycle-average WSS vector field. ResultsConvergence of the solution of the AD problem required the simulation of 3 (coronary artery) to 10 (aorta) additional cardiac cycles with respect to the Navier-Stokes problem. Co-localization results underlined that WSS topological skeleton features indicating near-wall flow stagnation and WSS attracting patterns identified LDL concentration polarization profiles more effectively than low WSS, as indicated by higher SI values (SI range: 0.17–0.50 for low WSS; 0.24–0.57 for WSS topological skeleton features). Moreover, the correspondence between the simulated LDL uptake and WSS-based quantities profiles with the in vivo measured wall thickness growth in coronary arteries appears promising. ConclusionsThe recently introduced Eulerian approach for identifying WSS attracting patterns from the divergence of normalized WSS provides a computationally affordable template of the LDL polarization at the arterial blood-wall interface without simulating the AD problem. It thus candidates as an effective biomechanical tool for elucidating the mechanistic link amongst LDL transfer at the arterial blood-wall interface, WSS and atherogenesis.

Brain Endothelial Cells in Contrary to the Aortic Do Not Transport but Degrade Low-Density Lipoproteins via Both LDLR and ALK1.

The transport of low-density lipoprotein (LDL) through the endothelium is a key step in the development of atherosclerosis, but it is notorious that phenotypic differences exist between endothelial cells originating from different vascular beds. Endothelial cells forming the blood–brain barrier restrict paracellular and transcellular passage of plasma proteins. Here, we systematically compared brain versus aortic endothelial cells towards their interaction with LDL and the role of proteins known to regulate the uptake of LDL by endothelial cells. Both brain endothelial cells and aortic endothelial cells bind and internalize LDL. However, whereas aortic endothelial cells degrade very small amounts of LDL and transcytose the majority, brain endothelial cells degrade but do not transport LDL. Using RNA interference (siRNA), we found that the LDLR–clathrin pathway leads to LDL degradation in either endothelial cell type. Both loss- and gain-of-function experiments showed that ALK1, which promotes transcellular LDL transport in aortic endothelial cells, also limits LDL degradation in brain endothelial cells. SR-BI and caveolin-1, which promote LDL uptake and transport into aortic endothelial cells, limit neither binding nor association of LDL to brain endothelial cells. Together, these results indicate distinct LDL trafficking by brain microvascular endothelial cells and aortic endothelial cells.

Atherogenesis, Transcytosis, and the Transmural Cholesterol Flux: A Critical Review.

The recently described phenomenon of cholesterol-loaded low-density lipoproteins (LDL) entering the arterial wall from the lumen by transcytosis has been accepted as an alternative for the long-held concept that atherogenesis involves only passive LDL movement across an injured or dysfunctional endothelial barrier. This active transport of LDL can now adequately explain why plaques (atheromas) appear under an intact, uninjured endothelium. However, the LDL transcytosis hypothesis is still questionable, mainly because the process serves no clear physiological purpose. Moreover, central components of the putative LDL transcytosis apparatus are shared by the counter process of cholesterol efflux and reverse cholesterol transport (RCT) and therefore can essentially create an energy-wasting futile cycle and paradoxically be pro- and antiatherogenic simultaneously. Hence, by critically reviewing the literature, we wish to put forward an alternative interpretation that, in our opinion, better fits the experimental evidence. We assert that most of the accumulating cholesterol (mainly as LDL) reaches the intima not from the lumen by transcytosis, but from the artery's inner layers: the adventitia and media. We have named this directional cholesterol transport transmural cholesterol flux (TCF). We suggest that excess cholesterol, diffusing from the avascular (i.e., devoid of blood and lymph vessels) media's smooth muscle cells, is cleared by the endothelium through its apical membrane. A plaque is formed when this cholesterol clearance rate lags behind its rate of arrival by TCF.

Multifaceted Protective Effects of Hesperidin by Aromatic Hydrocarbon Receptor in Endothelial Cell Injury Induced by Benzo[a]Pyrene.

Benzo[a]pyrene (BaP) causes atherosclerosis by activating the aromatic hydrocarbon receptor (AHR) signaling pathway to trigger lipid peroxidation and inflammation, thereby promoting the development of atherosclerosis. Hesperidin (Hsd), one of the 60 flavonoids of citrus, exhibits therapeutic effects on atherosclerosis. However, its antagonistic function for BaP remains unclear. In this study, the EA.hy926 cell model was used to systematically examine the antagonistic effect of Hsd with BaP, especially in low-density lipoprotein (LDL) oxidation and transport. Results showed that Hsd could reduce BaP-induced AHR activation in mRNA and protein expression level, and reduce LDL accumulation by decreasing the BaP-induced expression of advanced glycation end products and enhancing the BaP-inhibited Adenosine Triphosphate-binding cassette transporter A1 (ABCA1) protein and mRNA expression in EA.hy926 cells. In addition, Hsd could antagonize BaP-induced interaction of reactive oxygen species and the subsequent generation of oxidized LDL and malondialdehyde. Finally, Hsd could alleviate BaP-induced inflammatory response by decreasing IL-1β and TNF-α expression. All these results suggest that Hsd suppresses LDL accumulation, oxidation, and inflammatory response, and thus strongly impedes the AHR pathway activated by BaP.

Fluid\u2013structure interactions (FSI) based study of low-density lipoproteins (LDL) uptake in the left coronary artery

The purpose of this study is to compare the effect of the different physical factors on low-density lipoproteins (LDL) accumulation from flowing blood to the arterial wall of the left coronary arteries. The three-dimensional (3D) computational model of the left coronary arterial tree is reconstructed from a patient-specific computed tomography angiography (CTA) image. The endothelium of the coronary artery is represented by a shear stress dependent three-pore model. Fluid–structure interaction (FSI) based numerical method is used to study the LDL transport from vascular lumen into the arterial wall. The results show that the high elastic property of the arterial wall decreases the complexity of the local flow field in the coronary bifurcation system. The places of high levels of LDL uptake coincide with the regions of low wall shear stress. In addition, hypertension promotes LDL uptake from flowing blood in the arterial wall, while the thickened arterial wall decreases this process. The present computer strategy combining the methods of coronary CTA image 3D reconstruction, FSI simulation, and three-pore modeling was illustrated to be effective on the simulation of the distribution and the uptake of LDL. This may have great potential for the early prediction of the local atherosclerosis lesion in the human left coronary artery.

Non-Invasive Prediction of Site-Specific Coronary Atherosclerotic Plaque Progression using Lipidomics, Blood Flow, and LDL Transport Modeling

Background: coronary computed tomography angiography (CCTA) is a first line non-invasive imaging modality for detection of coronary atherosclerosis. Computational modeling with lipidomics analysis can be used for prediction of coronary atherosclerotic plaque progression. Methods: 187 patients (480 vessels) with stable coronary artery disease (CAD) undergoing CCTA scan at baseline and after 6.2 ± 1.4 years were selected from the SMARTool clinical study cohort (Clinicaltrial.gov Identifiers NCT04448691) according to a computed tomography (CT) scan image quality suitable for three-dimensional (3D) reconstruction of coronary arteries and the absence of implanted coronary stents. Clinical and biohumoral data were collected, and plasma lipidomics analysis was performed. Blood flow and low-density lipoprotein (LDL) transport were modeled using patient-specific data to estimate endothelial shear stress (ESS) and LDL accumulation based on a previously developed methodology. Additionally, non-invasive Fractional Flow Reserve (FFR) was calculated (SmartFFR). Plaque progression was defined as significant change of at least two of the morphological metrics: lumen area, plaque area, plaque burden. Results: a multi-parametric predictive model, including traditional risk factors, plasma lipids, 3D imaging parameters, and computational data demonstrated 88% accuracy to predict site-specific plaque progression, outperforming current computational models. Conclusions: Low ESS and LDL accumulation, estimated by computational modeling of CCTA imaging, can be used to predict site-specific progression of coronary atherosclerotic plaques.

Effect of Temperature-Dependent Blood Viscosity on Low-Density Lipoprotein Transport: Numerical Study

The blood viscosity is correlated with the risk of developing atherosclerotic lesions. The environmental factor can play an important role in altering hemodynamics and low-density lipoprotein (LDL) especially the ambient temperature. The greenhouse gas emission from energy or power production can increase the ambient temperature. This study investigated the effect of temperature-dependent blood viscosity on the LDL transport within the axisymmetric artery with a 40% stenosis blockage via computational fluid dynamics simulation. The results showed that the changing of blood viscosity inducing the change in pressure drop. The penetration locations of the LDL were also shifted which increased the risk of having LDL penetrating into the arterial wall. In addition, the outcome will contribute to the initial development of atherosclerosis modelling.

Micro-mechanism of low-density lipoproteins (LDL) transport in multi-layered arterial wall

This paper investigates micro-mechanism of LDL transport numerically in a multi-layer arterial wall. A novel comprehensive 3D model is developed by considering the coupling interactions between vascular layers, and numerical simulations are carried out for a two-layer structure arterial wall. Results displayed the effects of dynamic viscosity on LDL transport. Moreover, we present data demonstrating that endothelial cells have a great blocking effect on the permeation and transmission of macromolecules by the different vascular wall. Furthermore, to verify the reliability and efficiency, a comparison is presented which shows that our numerical results are in good consistency with the experimental data in the literature.

Effect of transport parameters on atherosclerotic lesion growth: A parameter sensitivity analysis

BackgroundAtherosclerosis is a degenerative disease of the arterial wall. It results in the formation of progressively growing plaque lesions that can harden and narrow their host arteries. Current computational models of the inflammatory process that govern atherosclerosis growth are reliant on a number of parameters that can freely vary and whose precise values are not well known. MethodsTo identify the significance of variation in such parameters, a parametric sensitivity study had been conducted on the blood density, blood viscosity, plasma viscosity and bulk flow low density lipoprotein (LDL) concentration. Using computational modeling, the significance of variation in these parameters was assessed on the transport of LDL. The simulation was performed via the 2k factorial experimental design, which was conducted to identify the significance of the select parameters on the intima LDL concentration and endothelial LDL coverage area. ResultsResults identified the blood viscosity and bulk flow LDL concentration are the dominant parameters for the atherosclerotic lesion growth. The coverage of LDL on the arterial wall surface was strongly dependent on the blood viscosity. The significance of these findings was discussed. ConclusionThis statistical study identifies two dominating blood factors, LDL concentration and blood viscosity, and how they influence atherosclerosis which will serves as a guideline for further investigation on the atherosclerosis topic.

A Mixture Theory Model for Blood Combined With Low-Density Lipoprotein Transport to Predict Early Atherosclerosis Regions in Idealized and Patient-Derived Abdominal Aorta.

Genesis and onset of atherosclerosis are greatly influenced by hemodynamic forces. Two-phase transient computational fluid dynamic (CFD) simulations are performed using a mixture theory model for blood, and a transport equation for low-density lipoprotein (LDL), in idealized and patient-derived abdominal aorta to predict the sites at risk for atherosclerosis. Flow patterns at different time instants and relevant hemodynamic indicators-wall shear stress (WSS)-based (time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT)), and LDL concentration-are used concurrently to predict the susceptible sites of atherosclerosis. In the case of idealized geometry, flow recirculations are observed on the posterior wall opposite the superior mesenteric artery and below the renal bifurcations. Low TAWSS, high OSI, high RRT and high concentration of LDL are observed in these regions. This suggests that in idealized abdominal aorta, the posterior wall proximal to the renal artery junction is more prone to atherosclerosis. This matches qualitatively with the experimental and simulation data in the literature. In the case of patient-derived geometry, flow reversal, low TAWSS, high OSI and high RRT are observed infrarenal on the anterior wall. Further, high concentration of LDL is observed at the same location on the anterior wall suggesting anterior wall distal to the renal artery junction is more prone to atherosclerosis. These findings demonstrate the use of a novel method to predict the sites at risk for atherosclerosis in geometries where complexities like junctions and curvature play a major role.

Interaction of different lipoprotein types with cholesterol at the air/water interface

Cholesterol (Chol) interacts with lipoproteins, in order to be transported through the aqueous bloodstream. High density lipoproteins (HDL) and low density lipoproteins (LDL) transport cholesterol differently, a result that may be due to a difference in their interactions with cholesterol. Here, we investigated how the lipoprotein type affects the interaction with cholesterol by using a Langmuir trough and fluorescence microscope. We studied pure monolayers of 1) Chol, 2) LDL, and 3) HDL, and mixed monolayers of 1) Chol-LDL, and 2) Chol-HDL at air/water interfaces. Images of the Chol-LDL mixed monolayer showed many small sterol domains distributed in the non-sterol molecules (e.g. phospholids, proteins and lipids) of LDL. The sterol domains that were seen in the Chol-HDL mixed monolayer were larger in size but smaller in number than those seen in the Chol-LDL mixed monolayers. These images and the excess area, excess free energy, and free energy of mixing values obtained from the thermodynamic analysis of the surface pressure-area per molecule isotherms suggested that the cholesterol phase separated more from HDL than from LDL. Cholesterol was therefore concluded to interact with LDL better than with HDL. This more favorable interaction was explained by the presence of hydrophobic interactions between cholesterol and Apo-B, the major apoprotein of LDL.

Elevated Lipid Infiltration Is Associated With Cerebral Aneurysm Rupture.

Background: Intracranial aneurysm wall degradation can be associated with lipid infiltration. However, the relationship between lipid infiltration and aneurysm rupture has not been explored quantitatively. To investigate the correlation between lipid infiltration and aneurysm rupture, we utilized patient-specific simulation of low-density lipoprotein (LDL) transport to analyze lipid infiltration in the cerebral aneurysm wall.Methods: Sixty-two aneurysms were analyzed. Patient blood pressure, plasma LDL concentration, and three-dimensional angiographic images were obtained to simulate LDL transport in aneurysms. Morphological, hemodynamic, and lipid accumulation parameters were compared between ruptures and unruptured groups. Multivariate logistic regression was also performed to determine parameters that are independently associated with rupture.Results: Size ratio, wall shear stress, low shear area, relative residence time, area-averaged LDL infiltration rate, and maximum LDL infiltration rate were significant parameters in univariate analysis (P < 0.05). Multivariate analysis revealed that only average LDL infiltration remained as a significant variable (P < 0.05). The prediction model derived showed good performance for rupture prediction (AUC, 0.885; 95% CI, 0.794–0.976).Conclusions: Ruptured aneurysms showed significantly higher LDL infiltration compared to unruptured ones. Our results suggested that lipid infiltration may promote aneurysm rupture. Lipid infiltration characteristics should be considered when assessing aneurysm rupture risk.

Pre-atherosclerotic flow and oncotically active solute transport across the arterial endothelium

Atherosclerosis starts with transmural (transwall) pressure-driven advective transport of blood-borne low-density lipoprotein (LDL) cholesterol across rare endothelial cell (EC) monolayer leaks into the arterial subendothelial intima (SI) wall layer where they can spread, bind to extracellular matrix and seed lesions. The local SI LDL concentration, which governs LDL’s binding kinetics, depends on the overall diluting transmural liquid flow. Transmural pressures typically compress the SI at physiological pressures, which keeps this flow low. Nguyen et al. (2015) showed that aortic ECs express the water channel protein aquaporin-1 (AQP1) and the transEC (δP) portion of the transmural (ΔP) pressure difference drives, in parallel, water across AQP1s and plasma across interEC junctions. Since the lumen is isotonic, selective AQP1-mediated water flow should quickly render the ECs’ lumen side hypertonic and the SI hypotonic; resulting transEC oncotic pressure differences, δπ, should oppose δP and quickly halt transEC flow. Yet Nguyen et al.’s (2015) transAQP1 flows persist for hours. To resolve this paradox, we extend our fluid filtration theory Joshi et al. (2015) to include mass transfer for oncotically active solutes like albumin. This addition nonlinearly couples mass transfer, fluid flow and wall mechanics. We simultaneously solve these problems at steady state. Surprisingly it finds that media layer filtration causes steady SI to exceed EC glycocalyx albumin concentration. Thus δπ reinforces rather than opposes δP, i.e., it sucks water from, rather than pushing water into the lumen from the SI. Endothelial AQP1s raise the overall driving force for flow across the EC above δP, most significantly at pressures too low to compress the SI, and they increase the ΔP needed for SI compression. This suggests the intriguing possibility that increasing EC AQP1 expression can raise this requisite compression pressure to physiological values. That is, increasing EC AQP1 may decompress the SI at physiological pressures, which would significantly increase SI thickness, flow and subsequently SI LDL dilution. This could retard LDL binding and delay preatherosclerotic lesion onset. The model also predicts that glycocalyx-degrading enzymes decrease overall transEC driving forces and thus lower, not raise, transmural water flux.

On the effects of straight extremities on low-density lipoprotein transport in the concentration boundary layer of curved arteries

Purpose The purpose of this paper is to analyze the influence of curvature on the transport of low-density lipoprotein (LDL) through a curved artery and concentration boundary layer characteristics numerically. Design/methodology/approach By using a projection method based on the second-order central difference discretization, the authors solve the set of governing equations, which consists of Navier–Stokes, continuity and species transport. The effects of initial straight length, as well as the curvature and wall shear stress (WSS) on LDL transport in a curved artery are established in this paper. Findings The obtained numerical results imply that the LDL concentration boundary layer thickness decreases in the outer part of the curved artery and increases in the inner part for both with or without initial straight length. The effect of Reynolds number on the concentration distribution in a curved artery with initial straight length is more pronounced than that on a fully curved artery, although an opposite trend was seen for the curvature ratio. The maximum surface LDL concentration is related to the regions with minimum WSS in the inner part of the curved artery, which has more potential the formation of atherosclerosis. Originality/value The authors present a comprehensive concentration distribution of LDL in the concentration boundary layer of the curved artery. The authors also characterize and predict the influence of curvature on the formation and development of atherosclerosis within the arterial wall.

Transfer of Low-Density Lipoproteins in Coronary Artery Bifurcation Lesions with Stenosed Side Branch: Numerical Study.

Evidence from clinical data suggests that the stenotic side branch (SB) is one of the key predictors for SB occlusion-based adverse events. In this study, we hypothesized that coronary bifurcations with stenotic SB might lead to severe concentration polarization of atherogenic lipids, such as the low-density lipoproteins (LDL), motivating the adverse events in the clinic. To confirm this hypothesis, this work numerically investigated the transport of LDL in different bifurcation lesions based on the Medina classification with various location and stenosis severities. The results showed that the coronary bifurcations with stenotic SB might be suffering more serious concentration polarization of LDL on the luminal surface of the SB due to higher level of LDL concentrations. Moreover, compared to the other bifurcation lesion types, the type (1,0,1) had the highest luminal surface LDL concentration along the SB and the highest degree of risk to enhance the process of atherosclerosis. In addition, this study also showed that the luminal surface LDL concentration increased with elevated stenosis severity. The type (1,0,1) with the severe stenosis (75% diameter reduction) had the highest concentration at the SB. In conclusion, these results suggested that both location of lesions and stenosis severities had great influence on the distribution of LDL on the luminal surface of the SB. Therefore, the estimation of disease severity and the interventional therapy should be carried out not only according to the stenosis severities in clinic. Moreover, compared to the other bifurcation lesion types, the type (1,0,1), rather than the type (1,1,1) as usually considered, had the highest luminal surface LDL concentration along the SB and the highest degree of risk to enhance the process of atherosclerosis.

A critical review on the applications of fluid-structure interaction in porous media

PurposeThis study aims to investigate a critical review on the applications of fluid-structure interaction (FSI) in porous media.Design/methodology/approachTransport phenomena in porous media are of continuing interest by many researchers in the literature because of its significant applications in engineering and biomedical sectors. Such applications include thermal management of high heat flux electronic devices, heat exchangers, thermal insulation in buildings, oil recovery, transport in biological tissues and tissue engineering. FSI is becoming an important tool in the design process to fully understand the interaction between fluids and structures.FindingsThis study is structured in three sections: the first part summarizes some important studies on the applications of porous medium and FSI in various engineering and biomedical applications. The second part focuses on the applications of FSI in porous media as related to hyperthermia. The third part of this review is allocated to the applications of FSI of convection flow and heat transfer in engineering systems filled with porous medium.Research limitations/implicationsTo the best knowledge of the present authors, FSI analysis of turbulent flow in porous medium never been studied, and therefore, more attention should be given to this area in any future studies. Moreover, more studies should also be conducted on mixed convective flow and heat transfer in systems using porous medium and FSI.Practical implicationsThe wall of the blood vessel is considered as a flexible multilayer porous medium, and therefore, rigid wall analysis is not accurate, and therefore, FSI should be implemented for accurate predictions of flow and hemodynamic stresses.Social implicationsThe use of porous media theory in biomedical applications received a great attention by many investigators in the literature (Khanafer and Vafai, 2006a; Al-Amiri et al., 2014; Lasiello et al., 2016a, Lasiello et al., 2016b; Lasiello et al., 2015; Chung and Vafai, 2013; Mahjoob and Vafai, 2009; Yang and Vafai, 2008; Yang and Vafai, 2006; Ai and Vafai, 2006). A comprehensive review was conducted by Khanafer and Vafai (2006b) summarizing various studies associated with magnetic field imaging and drug delivery. The authors illustrated that the tortuosity and porosity had a profound effect on the diffusion process within the brain. AlAmiri et al. (2014) conducted a numerical study to investigate the effect of turbulent pulsatile flow and heating technique on the thermal distribution within the arterial wall. The results of that investigation illustrated that local heat flux variation along the bottom layer of the tumor was greater for the low-velocity condition. Yang and Vafai (2006) presented a comprehensive four-layer model to study low-density lipoprotein transport in the arterial wall coupled with a lumen (Figure 1). All the four layers (endothelium, intima, internal elastic lamina and media) were modeled as a homogenous porous medium.Originality/valueFuture studies on the applications of FSI in porous media are recommended in this review.