Local Hemodynamic Environment Research Articles

Description of the local hemodynamic environment in intracranial aneurysm wall subdivisions.

Intracranial aneurysms (IAs) pose severe health risks influenced by hemodynamics. This study focuses on the intricate characterization of hemodynamic conditions within the IA walls and their influence on bleb development, aiming to enhance understanding of aneurysm stability and the risk of rupture. The methods emphasized utilizing a comprehensive dataset of 359 IAs and 213 IA blebs from 268 patients to reconstruct patient-specific vascular models, analyzing blood flow using finite element methods to solve the unsteady Navier-Stokes equations, the segmentation of aneurysm wall subregions and the hemodynamic metrics wall shear stress (WSS), its metrics, and the critical points in WSS fields were computed and analyzed across different aneurysm subregions defined by saccular, streamwise, and topographical divisions. The results revealed significant variations in these metrics, correlating distinct hemodynamic environments with wall features on the aneurysm walls, such as bleb formation. Critical findings indicated that regions with low WSS and high OSI, particularly in the body and central regions of aneurysms, are prone to conditions that promote bleb formation. Conversely, areas exposed to high WSS and positive divergence, like the aneurysm neck, inflow, and outflow regions, exhibited a different but substantial risk profile for bleb development, influenced by flow impingements and convergences. These insights highlight the complexity of aneurysm behavior, suggesting that both high and low-shear environments can contribute to aneurysm pathology through distinct mechanisms.

Experimental validation and clinical feasibility of 3D reconstruction of coronary artery bifurcation stents using intravascular ultrasound.

The structural morphology of coronary stents and the local hemodynamic environment following stent deployment in coronary arteries are crucial determinants of procedural success and subsequent clinical outcomes. High-resolution intracoronary imaging has the potential to facilitate geometrically accurate three-dimensional (3D) reconstruction of coronary stents. This work presents an innovative algorithm for the 3D reconstruction of coronary artery stents, leveraging intravascular ultrasound (IVUS) and angiography. The accuracy and reproducibility of our method were tested in stented patient-specific silicone models, with micro-computed tomography serving as a reference standard. We also evaluated the clinical feasibility and ability to perform computational fluid dynamics (CFD) studies in a clinically stented coronary bifurcation. Our experimental and clinical studies demonstrated that our proposed algorithm could reproduce the complex 3D stent configuration with a high degree of precision and reproducibility. Moreover, the algorithm was proved clinically feasible in cases with stents deployed in a diseased coronary artery bifurcation, enabling CFD studies to assess the hemodynamic environment. In combination with patient-specific CFD studies, our method can be applied to stenting optimization, training in stenting techniques, and advancements in stent research and development.

The influence of flow distribution strategy for the quantification of pressure- and wall shear stress-derived parameters in the coronary artery: A CTA-based computational fluid dynamics analysis

For image-based computational fluid dynamics (CFD) analysis to characterize the local coronary hemodynamic environment, the accuracy depends on the flow rate which is in turn associated with outlet branches’ morphology. A good flow distribution strategy is important to mitigate the effect when certain branches cannot be considered. In this study, stenotic coronary arteries from 13 patients were used to analyze the effect of missing branches and different flow distribution strategies. Pressure- and wall shear stress (WSS)-derived parameters around the stenotic region (ROI) were compared, including fractional flow reserve (CT-FFR), instantaneous wave-free ratio (CT-iFR), resting distal to aortic coronary pressure (CT-Pd/Pa), time-averaged WSS, oscillatory shear index (OSI) and relative residence time (RRT). Three flow distribution strategies were the Huo-Kassab model at distal outlets (Type I), flow distribution based on outlet resistances (Type II), and a developed algorithm distributing flow at each bifurcation until the final outlets (Type III). Results showed that Type III strategy for models with truncated branch(es) had a good agreement in both pressure- and WSS-related results (interquatile range less than 0.12% and 4.02%, respectively) with the baseline model around the ROI. The relative difference of pressure- and WSS-related results were correlated with the flow differences in the ROI to the baseline mode. Type III strategy had the best performance in maintaining the flow in intermediate branches. It is recommended for CFD analysis. Removal of branches distal to a stenosis can be undertaken with an improved performance and maintained accuracy, while those proximal to the ROI should be kept.

Hostile Hemodynamics in Distal Stent Graft-Induced New Entry Prior to Aortic Rupture: A Comparison of Transient versus Steady-State CFD Simulations.

Computational fluid dynamics (CFD) simulations model blood flow in aortic pathologies. The aim of our study was to understand the local hemodynamic environment at the site of rupture in distal stent graft-induced new entry (dSINE) after frozen elephant trunk with a clinically time efficient steady-flow simulation versus transient simulations. Steady-state simulations were performed for dSINE, prior and after its development and prior to aortic rupture. To account for potential turbulences due geometric changes at the dSINE location, Reynolds-averaged Navier-Stokes equations with the realizable k-ε model for turbulences were applied. Transient simulations were performed for comparison. Hemodynamic parameters were assessed at various locations of the aorta. Post-dSINE, jet-like flow due to luminal narrowing was observed which increased prior to rupture and resulted in focal neighbored regions of high and low wall shear stress (WSS). Prior to rupture, aortic diameter at the rupture site increased lowering WSS at the entire aortic circumference. Concurrently, WSS and turbulence increased locally above the entry tear at the inner aortic curvature. Turbulent kinetic energy and WSS elevation in the downstream aorta demonstrated enhanced stress on the native aorta. Results of steady-state simulations were in good qualitative agreement with transient simulations. Steady-flow CFD simulations feasible at clinical time scales prior to aortic rupture reveal a hostile hemodynamic environment at the dSINE rupture site in agreement with lengthy transient simulations. Consequently, our developed approach may be of value in treatment planning where a fast assessment of the local hemodynamic environment is essential.

Computational Fluid Dynamics in Intracranial Atherosclerotic Disease

Recurrent stroke risk in intracranial atherosclerotic disease remains high despite aggressive medical therapy. While hemodynamic insufficiency appears to be a strong marker of stroke recurrence, natural history studies using various unimodal imaging modalities have shown mixed results, as they likely do not adequately capture the complex local hemodynamic environment generated by a focal stenosis. Computational fluid dynamics, a multimodal tool used to simulate fluid flow and the interactions between fluids and surfaces, has recently been used to illustrate the complex hemodynamic environment surrounding intracranial atherosclerotic lesions and to risk‐stratify patients on the basis of simulated outputs. We aimed to summarize the literature pertaining to computational fluid dynamics use in intracranial atherosclerotic disease and to describe its future potential use in generating more targeted therapies.

Photomodulated Extrusion as a Localized Endovascular Hydrogel Deposition Method.

Minimally invasive endovascular embolization is used to treat a wide range of diseases in neurology, oncology, and trauma where the vascular morphologies and corresponding hemodynamics vary greatly. Current techniques based on metallic coils, flow diverters, liquid embolics, and suspended microspheres are limited in their ability to address a wide variety of vasculature and can be plagued by complications including distal migration, compaction, and inappropriate vascular remodeling. Further, these endovascular devices currently offer limited therapeutic functions beyond flow control such as drug delivery. Herein, a novel in situ microcatheter-based photomodulated extrusion approach capable of dynamically tuning the physical and morphological properties of injectable hydrogels, optimizing for local hemodynamic environment and vascular morphology, is proposed and demonstrated. A shear thinning and photoactivated poly(ethylene glycol diacrylate)-nanosilicate (PEGDA-nSi) hydrogel is used to demonstrate multiple extrusion modes which are controlled by photokinetics and device configurations. Real-time photomodulation of injected hydrogel viscosity and modulus is successfully used for embolization in various vasculatures, including high-flow large vessels and arterial-to-arterial capillary shunts. Furthermore, a generalizable therapeutic delivery platform is proposed by demonstrating a core-shell structured extrusion encapsulating doxorubicin to achieve a more sustained release compared to unencapsulated payload.

The effect of subbranch for the quantification of local hemodynamic environment in the coronary artery: a computed tomography angiography–based computational fluid dynamic analysis

Abstract Background Hemodynamic parameters derived from computed tomography angiography–based computational fluid dynamics (CFD) analysis have been widely used for clinical decision-making and researches to assess the vulnerability of atherosclerotic plaques and explain the initialization and development of atherosclerosis. Subbranches in the CFD model might affect the accuracy of hemodynamic parameters, but the effectiveness has been least quantified. Methods A coronary artery baseline model was generated with focal stenosis at the proximal left anterior descending artery. Nineteen comparing models were created by systematically removing various subbranches to examine the changes in hemodynamic parameters, including time-averaged pressure (TAP), time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and particle relative residence time (RRT). Changes in these parameters were assessed quantitatively around the stenosis and near the region where subbranches were removed. Results The removal of subbranches caused a significant change in outflow rate, and there was generally a decrease in all CFD parameters in the regions of interest with a decrease in outflow rate. The subbranch removal had a significant impact on the calculation of TAWSS, OSI, and RRT, whereas TAP was insensitive to the removal with approximately 0.25% variation in all 19 models. The local effect from removing branch segments generally became negligible after 5 diameters away from the cutting-off position, but the decrease could be affected by other factors, such as a large curvature. Conclusion The outflow rate is a dominant factor for the calculation of TAP, TAWSS, OSI, and RRT. Removal of subbranches has a minor effect on the TAP calculation, but its effect is considerable on the TAWSS, OSI, and RRT. The effect of subbranch removal is limited in a region with 5 local diameters.

Hemodynamic impact of proximal anterior cerebral artery aneurysm: Mind the posteriorly projecting ones!

Intracranial aneurysm projected posteriorly is associated with high risk of aneurysm rupture. In order to investigate the biomechanical mechanisms for the adverse event, three-dimension intracranial cerebral aneurysms were constructed based on clinical data, and we numerically compared effect of location, position, size, and shape of aneurysm on hemodynamic conditions including velocity, pressure, and wall shear stress (WSS). The numerical results showed that the aneurysm projected posteriorly even at small sizes led to abnormal hemodynamic environment, which was featured by a local high pressure and stress concentration near aneurysm neck area. Moreover, the one located at the proximal A1 segment and ellipsoidal aneurysm would further worse local hemodynamic environment, causing high local stresses. These findings indicated the potential mechanical mechanism for high rupture rate of the aneurysms projected posteriorly, underscoring importance of early and accurate diagnosis and promptly treatment for improved the clinical outcome, even if these aneurysms are of small sizes.

Effect of Anastomosis Angles on Retrograde Perfusion and Hemodynamics of Hybrid Treatment for Thoracoabdominal Aortic Aneurysm

Hemodynamic effects on the retrograde visceral reconstruction (RVR) for thoracoabdominal aortic aneurysms treatment by anastomotic angle remains unclear. This study aims to qualitatively and quantitatively investigate the effects of different anastomotic angles on hemodynamics and patency. Three RVR models with 45°, 60° and 90° anastomotic angles were reconstructed respectively by manipulating apostoperative patient-specific model. The manipulated models of the RVRs were numerically simulated and analyzed in terms of hemodynamics including theinstant and cumulative patency, flow pattern and indicators based on wall shear stress (WSS). Although a smaller anastomotic angle may decrease the patency rate of common iliac arteries, it can improve the visceral perfusion during a cardiac cycle. More importantly, RVR with the smallest anastomotic angle experienced a minimal low time-averaged wall shear stress, high oscillatory shear index and relative residence time in the anastomosis region, whereas the largest anastomotic angle can introduce more unfavorable WSS in the graft trunk. Furthermore, a spiral flow pattern was observed in the proximal graft trunk of all three models, where no high-risk shear distribution was detected in this region. A smaller anastomotic angle may have more benefits of hemodynamic environment in RVR, especially the WSS distribution and flow pattern in the graft trunk. We may also suggest that additional stents or an extended cuff for the graft can be used to induce spiral flow intentionally, which can further improve local hemodynamic environment and long-term prognosis.

Image-based patient-specific flow simulations are consistent with stroke in pediatric cerebrovascular disease.

Moyamoya disease (MMD) is characterized by narrowing of the distal internal carotid artery and the circle of Willis (CoW) and leads to recurring ischemic and hemorrhagic stroke. A retrospective review of data from 50 pediatric MMD patients revealed that among the 24 who had a unilateral stroke and were surgically treated, 11 (45.8%) had a subsequent, contralateral stroke. There is no reliable way to predict these events. After a pilot study in Acta-/- mice that have features of MMD, we hypothesized that local hemodynamics are predictive of contralateral strokes and sought to develop a patient-specific analysis framework to noninvasively assess this stroke risk. A pediatric MMD patient with an occlusion in the right middle cerebral artery and a right-sided stroke, who was surgically treated and then had a contralateral stroke, was selected for analysis. By using an unsteady Navier-Stokes solver within an isogeometric analysis framework, blood flow was simulated in the CoW model reconstructed from the patient's postoperative imaging data, and the results were compared with those from an age- and sex-matched control subject. A wall shear rate (WSR) > 60,000s-1 (about 12 × higher than the coagulation threshold of 5000s-1 and 9 × higher than control) was measured in the terminal left supraclinoid artery; its location coincided with that of the subsequent postsurgical left-sided stroke. A parametric study of disease progression revealed a strong correlation between the degree of vascular morphology altered by MMD and local hemodynamic environment. The results suggest that an occlusion in the CoW could lead to excessive contralateral WSRs, resulting in thromboembolic ischemic events, and that WSR could be a predictor of future stroke.

Three dimensional reconstruction of coronary artery stents from optical coherence tomography: experimental validation and clinical feasibility

The structural morphology of coronary stents (e.g. stent expansion, lumen scaffolding, strut apposition, tissue protrusion, side branch jailing, strut fracture), and the local hemodynamic environment after stent deployment are key determinants of procedural success and subsequent clinical outcomes. High-resolution intracoronary imaging has the potential to enable the geometrically accurate three-dimensional (3D) reconstruction of coronary stents. The aim of this work was to present a novel algorithm for 3D stent reconstruction of coronary artery stents based on optical coherence tomography (OCT) and angiography, and test experimentally its accuracy, reproducibility, clinical feasibility, and ability to perform computational fluid dynamics (CFD) studies. Our method has the following steps: 3D lumen reconstruction based on OCT and angiography, stent strut segmentation in OCT images, packaging, rotation and straightening of the segmented struts, planar unrolling of the segmented struts, planar stent wireframe reconstruction, rolling back of the planar stent wireframe to the 3D reconstructed lumen, and final stent volume reconstruction. We tested the accuracy and reproducibility of our method in stented patient-specific silicone models using micro-computed tomography (μCT) and stereoscopy as references. The clinical feasibility and CFD studies were performed in clinically stented coronary bifurcations. The experimental and clinical studies showed that our algorithm (1) can reproduce the complex spatial stent configuration with high precision and reproducibility, (2) is feasible in 3D reconstructing stents deployed in bifurcations, and (3) enables CFD studies to assess the local hemodynamic environment within the stent. Notably, the high accuracy of our algorithm was consistent across different stent designs and diameters. Our method coupled with patient-specific CFD studies can lay the ground for optimization of stenting procedures, patient-specific computational stenting simulations, and research and development of new stent scaffolds and stenting techniques.

Local hemodynamic analysis after coronary stent implantation based on Euler-Lagrange method.

Coronary stents are deployed to treat the coronary artery disease (CAD) by reopening stenotic regions in arteries to restore blood flow, but the risk of the in-stent restenosis (ISR) is high after stent implantation. One of the reasons is that stent implantation induces changes in local hemodynamic environment, so it is of vital importance to study the blood flow in stented arteries. Based on regarding the red blood cell (RBC) as a rigid solid particle and regarding the blood (including RBCs and plasma) as particle suspensions, a non-Newtonian particle suspensions model is proposed to simulate the realistic blood flow in this work. It considers the blood's flow pattern and non-Newtonian characteristic, the blood cell-cell interactions, and the additional effects owing to the bi-concave shape and rotation of the RBC. Then, it is compared with other four common hemodynamic models (Newtonian single-phase flow model, Newtonian Eulerian two-phase flow model, non-Newtonian single-phase flow model, non-Newtonian Eulerian two-phase flow model), and the comparison results indicate that the models with the non-Newtonian characteristic are more suitable to describe the realistic blood flow. Afterwards, based on the non-Newtonian particle suspensions model, the local hemodynamic environment in stented arteries is investigated. The result shows that the stent strut protrusion into the flow stream would be likely to produce the flow stagnation zone. And the stent implantation can make the pressure gradient distribution uneven. Besides, the wall shear stress (WSS) of the region adjacent to every stent strut is lower than 0.5Pa, and along the flow direction, the low-WSS zone near the strut behind is larger than that near the front strut. What's more, in the regions near the struts in the proximal of the stent, the RBC particle stagnation zone is easy to be formed, and the erosion and deposition of RBCs are prone to occur. These hemodynamic analyses illustrate that the risk of ISR is high in the regions adjacent to the struts in the proximal and the distal ends of the stent when compared with struts in other positions of the stent. So the research can provide a suggestion on the stent design, which indicates that the strut structure in these positions of a stent should be optimized further.

The effect of stenosis rate and Reynolds number on local flow characteristics and plaque formation around the atherosclerotic stenosis

Atherosclerosis causes plaque to build-up in arteries. Effect of the specific local hemodynamic environment around an atherosclerotic plaque on the thrombosis formation does not remain quite clear but is believed to be crucial. The aim of this study is to uncover the flow effects on plaques formation. To study the mechanically regulated plaque formation, the flow fields in artery blood vessels with different stenosis rates at various Reynolds numbers were simulated numerically with the two-dimensional axisymmetric models, and the hemodynamic characteristics around the plaque were scaled with stenosis rate and Reynolds number. The results showed that increases of both Reynolds number and stenosis rate facilitated the occurrence of flow separation phenomenon, extended recirculation zone, and upregulated the maximum normalized wall shear stress near the plaque throat section while downregulated the minimal normalized wall shear stress at the front shoulder of plaque, as it should be; in the atherosclerotic plaque leeside of the recirculation zone, an obvious catch bond region of wall shear stress might exist especially under low Reynolds number with stenosis rate smaller than 30%. This catch bond region in the plaque leeside might be responsible for the LBF (low blood flow)-enhanced formation of the atherosclerotic plaque. This work may provide a novel insight into understanding the biomechanical effects behind the formation and damage of atherosclerotic plaques and propose a new strategy for preventing atherosclerotic diseases.

T and Small Protrusion (TAP) vs Double-Kissing Crush Technique: Insights From In Vitro Models

BackgroundPercutaneous coronary interventions on complex bifurcation lesions may require implantation of two stents to appropriately treat diffuse side-branch (SB) disease. Comparisons among different bifurcation stenting techniques are continuously attempted by various study designs (bench tests, computer simulations, clinical studies). Among different techniques, double kissing crush (DKC) represents the last evolution for “crushing” while T and small Protrusion (TAP) represents the evolution of “T stenting”. Both techniques are actually gaining popularity, but head-to-head comparisons are lacking. Methods and resultsTwo last generation drug-eluting stents (Synergy™, Boston Scientific, MA, USA and Ultimaster™,Terumo Corp., Japan) were implanted in left main bifurcation bench models using TAP (n = 6 sets) and DKC (n = 6 sets) techniques. A peristaltic pump with fresh porcine blood was used to perfuse the blood through the silicone model at a flow rate of 200 ml/min for 4 min. Optical coherence tomography (OCT) was used to assess stent struts geometry and thrombus formation. SB cross sectional area as well as SB obstruction did not significantly differ between the two techniques. Numerical (but not statistically significant) differences were found in terms of malapposed struts (fewer with TAP) and floating struts (fewer with DKC). Thrombus formation after blood perfusion was similar between TAP and DKC technique (1.53 ± 1.12 vs. 1.20 ± 1.01 mm2, p = 0.6). ConclusionThe result of the present in-vitro study shows the absence of significant difference between TAP and DKC in terms of stent struts apposition and acute thrombus formation potential. Despite the completely different technical steps required, both techniques have similar performance according to such articulated pre-clinical evaluation. What is already known about this subject?Due to its limited complexity, T and Protrusion (TAP) technique is considered the to-go technique for bifurcation lesions with good long-term results. Recently, double kissing crush (DKC) technique has been gaining popularity and demonstrated promising results in randomized clinical trials. What does this study add?This in-vitro bench test study provides a unique detailed OCT comparison and local hemodynamic environment analysis of the two techniques. How might this impact on clinical practice?New insights of acute thrombogenicity and computational flow model simulation may guide percutaneous therapeutic strategies of bifurcation lesions.

Influence of Artery Straightening on Local Hemodynamics in Left Anterior Descending (LAD) Artery after Stent Implantation.

Objectives The study investigates local hemodynamic environment changes caused by straightening phenomenon and the relationship between straightening phenomenon and in-stent restenosis. Background Intravascular intervention is an effective treatment in restoring the normal flow conditions and vascular lumen. Unfortunately, in-stent restenosis often occurs in a subset of patients after stent implantation and limits the success of stent implantation outcomes. The implanted stent usually causes artery straightening locally, rather than coinciding and adjusting to the physiological curve exactly. Artery straightening would apparently modify the artery geometry and therefore alter the local hemodynamic environment, which may result in intimal hyperplasia and restenosis after stenting implantation. Methods In the current investigation, we verify the hypothesis that the artery straightening influences the local hemodynamic state using the different 3D CT models. Flow analysis for blood in the left anterior descending coronary artery and the straightening model is simulated numerically. Result The current results reveal that the straightening phenomenon alters the distribution of wall shear stress and flow patterns, decreases the wall shear stress (WSS), and increases the oscillatory shear index (OSI) and the relative residence time (RRT), especially at the proximal and distal areas of stenting. Conclusions The local straightened geometry established after stent implantation was likely to generate portions of the stenting area to a high risk of neointimal hyperplasia and subsequent restenosis.

Structural and Hemodynamic Analyses of Different Stent Structures in Curved and Stenotic Coronary Artery.

Coronary artery stenting is commonly used for the treatment of coronary stenosis, and different stent structures indeed have various impacts on the stress distribution within the plaque and artery as well as the local hemodynamic environment. This study aims to evaluate the performance of different stent structures by characterizing the mechanical parameters after coronary stenting. Six stent structures including three commercially-shaped stents (Palmaz-Schatz-shaped, Xience Prime-shaped, and Cypher-shaped) and three author-developed stents (C-Rlink, C-Rcrown, and C-Astrut) implanted into a curved stenotic coronary artery were investigated. Structural analyses of the balloon-stent-plaque-artery system were first performed, and then followed by hemodynamic analyses. The results showed that among the three commercially-shaped stents, the Palmaz-Schatz-shaped had the least stent dogboning and recoiling, corresponding to the greatest maximum plastic strain and the largest diameter change, nevertheless, it induced the highest maximum von Mises stress on plaque, arterial intima and media. From the viewpoint of hemodynamics, the Palmaz-Schatz-shaped displayed smaller areas of adverse low wall shear stress (<0.5 Pa), low time-averaged wall shear stress (<0.5 Pa), and high oscillating shear index (>0.1). Compared to the Cypher-shaped, the C-Rcrown and C-Astrut had smaller recoiling, greater maximum plastic stain and larger diameter change, which indicated the improved mechanical performance of the Cypher-shaped stent. Moreover, both C-Rcrown and C-Astrut exhibited smaller areas of adverse low wall shear stress, and low time-averaged wall shear stress, but only the C-Rcrown displayed a smaller area of adverse high oscillating shear index. The present study evaluated and compared the performance of six different stents deployed inside a curved artery, and could be potentially utilized as a guide for the selection of suitable commercially-shaped stent for clinical application, and to provide an approach to improve the performance of the commercial stents.

Carotid Bifurcation With Tandem Stenosis-A Patient-Specific Case Study Combined in vivo Imaging, in vitro Histology and in silico Simulation.

A patient-specific carotid bifurcation with tandem stenosis found at both internal carotid artery (ICA) and common carotid artery (CCA) was studied. The in vivo pre-carotid endarterectomy (pre-CEA) multi-spectral magnetic resonance imaging (MRI) were performed and in vitro post-CEA carotid plaque tissue sample was collected. MR imaging data and tissue sample staining histology were used to recognize the plaque components. Further, the computational fluid dynamics (CFD) were performed on four MR-based reconstructed 3D carotid bifurcation models (the patient-specific geometry with tandem stenosis and three presumptive geometries by removing the stenosis part). The flow and shear stress behavior affected by the tandem stenosis was analyzed. From the results of MR segmentation and histology analysis, plaque lipid pool and calcification were found at both ICA and CCA. From the result of CFD simulation, the flow shear stress behavior suggested the tandem stenosis as a more “dangerous” situation than a single-stenosis artery. Besides, the CFD results deduced that the stenosis at the CCA location formed initially and led to the subsequent formation of stenosis at ICA. This study suggests that when planning CEA, CFD simulation on the presumptive models could help clinicians to estimate the blood flow behavior after surgery. Particular attention should be paid to the case of tandem stenosis, as the local hemodynamic environment is more complex and treatment of one stenosis may lead to a variation in the hemodynamic loading on the second plaque, which may result in either a higher risk of plaque rupture or restenosis.

Inositol trisphosphate dynamics underlie physiological calcium signals within the coronary artery endothelium

The arterial endothelium modulates smooth muscle tone in response to its local hemodynamic environment. This process is critical to normal vascular function, and is impaired by endothelial cell injury in coronary artery disease. Last year, we discovered a unique mode of calcium signaling of the porcine coronary artery endothelium, characterized by a pattern of continuous, cell‐wide calcium waves in the absence of agonist stimulation. Stimulation with substance P (10−13 to 10−6 ml/L) amplified this pattern to match dose‐dependent vessel relaxation responses. Here, we investigated the mechanism underlying the formation of this characteristic pattern of endothelial calcium waves with confocal microscopy, utilizing both pharmacological and computational approaches. We found that coronary endothelial cell calcium waves were mediated by inositol trisphosphate receptors (IP3R), which exhibited distinct intracellular isoform distributions. The distribution of the type 1 IP3R isoform corresponded to the area (33.9 ± 2.6 μm2) of propagating calcium waves, including perinuclear IP3R clustering at subcellular sites of constitutively elevated calcium. We utilized a computational model of calcium signaling that included this distinct IP3R distribution, and discovered that cell‐wide waves formed only if intracellular concentration gradients of inositol trisphosphate (IP3) were present along the longitudinal cell axis. Importantly, we found that production and diffusion of IP3 from a focal intracellular source was sufficient to initiate a calcium wave event with the same propagation velocity curve (mean: 6.08 ± 0.61 μm/s) of the experimentally‐observed wave. Furthermore, amplification of IP3 production in our model resulted in an increase of the frequency of elementary wave events which reflected the dose‐dependent expansion of calcium activity induced by substance P. These results indicate a fundamental role for IP3 dynamics as a physiological mediator of vascular responses, underlying both the initiation and expansion of unique endothelial calcium signal modalities.Support or Funding InformationThis work was supported by NIH grants: HL136869, HL085887, and S10RR027535.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

TCT-567 In Vivo Reconstruction of Bioresorbable Stents and Its Impact on Computation of Shear Stress

The implantation of bioresorbable stents (BVS) alters the local hemodynamic environment. Computational fluid dynamics (CFD) allows evaluation of local flow pattern and shear stress (SS). The aim of this study was to develop a new approach for in vivo reconstruction of BVS after implantation and to

Flow-dependent YAP/TAZ activities regulate endothelial phenotypes and atherosclerosis

The focal nature of atherosclerotic lesions suggests an important role of local hemodynamic environment. Recent studies have demonstrated significant roles of Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) in mediating mechanotransduction and vascular homeostasis. The objective of this study is to investigate the functional role of YAP/TAZ in the flow regulation of atheroprone endothelial phenotypes and the consequential development of atherosclerotic lesions. We found that exposure of cultured endothelial cells (ECs) to the atheroprone disturbed flow resulted in YAP/TAZ activation and translocation into EC nucleus to up-regulate the target genes, including cysteine-rich angiogenic inducer 61 (CYR61), connective tissue growth factor (CTGF), and ankyrin repeat domain 1 (ANKRD1). In contrast, the athero-protective laminar flow suppressed YAP/TAZ activities. En face analysis of mouse arteries demonstrated an increased nuclear localization of YAP/TAZ and elevated levels of the target genes in the endothelium in atheroprone areas compared with athero-protective areas. YAP/TAZ knockdown significantly attenuated the disturbed flow induction of EC proliferative and proinflammatory phenotypes, whereas overexpression of constitutively active YAP was sufficient to promote EC proliferation and inflammation. In addition, treatment with statin, an antiatherosclerotic drug, inhibited YAP/TAZ activities to diminish the disturbed flow-induced proliferation and inflammation. In vivo blockade of YAP/TAZ translation by morpholino oligos significantly reduced endothelial inflammation and the size of atherosclerotic lesions. Our results demonstrate a critical role of the activation of YAP/TAZ by disturbed flow in promoting atheroprone phenotypes and atherosclerotic lesion development. Therefore, inhibition of YAP/TAZ activation is a promising athero-protective therapeutic strategy.