scholarly journals Alagebrium inhibits neointimal hyperplasia and restores distributions of wall shear stress by reducing downstream vascular resistance in obese and diabetic rats

2015 ◽  
Vol 309 (7) ◽  
pp. H1130-H1140 ◽  
Author(s):  
Hongfeng Wang ◽  
Dorothee Weihrauch ◽  
Judy R. Kersten ◽  
Jeffrey M. Toth ◽  
Anthony G. Passerini ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Vascular Resistance ◽  
Transforming Growth Factor ◽  
Oxidized Ldl ◽  
Neointimal Hyperplasia ◽  
Ldl Receptor ◽  
Transforming Growth Factor Β ◽  
Age Related ◽  
Wall Shear

Mechanisms of restenosis in type 2 diabetes mellitus (T2DM) are incompletely elucidated, but advanced glycation end-product (AGE)-induced vascular remodeling likely contributes. We tested the hypothesis that AGE-related collagen cross-linking (ARCC) leads to increased downstream vascular resistance and altered in-stent hemodynamics, thereby promoting neointimal hyperplasia (NH) in T2DM. We proposed that decreasing ARCC with ALT-711 (Alagebrium) would mitigate this response. Abdominal aortic stents were implanted in Zucker lean (ZL), obese (ZO), and diabetic (ZD) rats. Blood flow, vessel diameter, and wall shear stress (WSS) were calculated after 21 days, and NH was quantified. Arterial segments (aorta, carotid, iliac, femoral, and arterioles) were harvested to detect ARCC and protein expression, including transforming growth factor-β (TGF-β) and receptor for AGEs (RAGE). Downstream resistance was elevated (60%), whereas flow and WSS were significantly decreased (44% and 56%) in ZD vs. ZL rats. NH was increased in ZO but not ZD rats. ALT-711 reduced ARCC and resistance (46%) in ZD rats while decreasing NH and producing similar in-stent WSS across groups. No consistent differences in RAGE or TGF-β expression were observed in arterial segments. ALT-711 modified lectin-type oxidized LDL receptor 1 but not RAGE expression by cells on decellularized matrices. In conclusion, ALT-711 decreased ARCC, increased in-stent flow rate, and reduced NH in ZO and ZD rats through RAGE-independent pathways. The study supports an important role for AGE-induced remodeling within and downstream of stent implantation to promote enhanced NH in T2DM.

Accurate Prediction of Wall Shear Stress in a Stented Artery: Newtonian Versus Non-Newtonian Models

2011 ◽  
Vol 133 (7) ◽  
Author(s):  
Juan Mejia ◽  
Rosaire Mongrain ◽  
Olivier F. Bertrand
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Linear Model ◽  
Newtonian Fluid ◽  
Nonlinear Model ◽  
Numerical Models ◽  
Neointimal Hyperplasia ◽  
Computational Cost ◽  
Arterial Segment ◽  
Wall Shear

A significant amount of evidence linking wall shear stress to neointimal hyperplasia has been reported in the literature. As a result, numerical and experimental models have been created to study the influence of stent design on wall shear stress. Traditionally, blood has been assumed to behave as a Newtonian fluid, but recently that assumption has been challenged. The use of a linear model; however, can reduce computational cost, and allow the use of Newtonian fluids (e.g., glycerine and water) instead of a blood analog fluid in an experimental setup. Therefore, it is of interest whether a linear model can be used to accurately predict the wall shear stress caused by a non-Newtonian fluid such as blood within a stented arterial segment. The present work compares the resulting wall shear stress obtained using two linear and one nonlinear model under the same flow waveform. All numerical models are fully three-dimensional, transient, and incorporate a realistic stent geometry. It is shown that traditional linear models (based on blood’s lowest viscosity limit, 3.5 Pa s) underestimate the wall shear stress within a stented arterial segment, which can lead to an overestimation of the risk of restenosis. The second linear model, which uses a characteristic viscosity (based on an average strain rate, 4.7 Pa s), results in higher wall shear stress levels, but which are still substantially below those of the nonlinear model. It is therefore shown that nonlinear models result in more accurate predictions of wall shear stress within a stented arterial segment.

Abstract 14689: Regional Aortic Wall Shear Stress Mapping Implicates Hemodynamics in Human Bicuspid Aortopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
David G Guzzardi ◽  
Pim van Ooij ◽  
Alex J Barker ◽  
Giampaolo Martufi ◽  
Katherine E Olsen ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Aortic Wall ◽  
Transforming Growth Factor ◽  
Patient Specific ◽  
4D Flow Mri ◽  
4D Flow ◽  
Hemodynamic Assessment ◽  
Flow Mri ◽  
Wall Shear

Introduction: A suspected genetic cause for bicuspid aortic valve (BAV) aortopathy has led to aggressive resection strategies. Using 4D flow MRI, we documented increased regional wall shear stress (WSS) in BAV patients. Local hemodynamics may exacerbate extracellular matrix (ECM) degradation leading to disease progression. If validated, preoperative regional hemodynamic assessment could be used to guide more targeted patient-specific aortic resection. For the first time, we correlated regional WSS with aortic tissue remodeling in BAV patients. Methods & Results: BAV patients (N=11) undergoing ascending aortic resection received preoperative 4D flow MRI with regional WSS differences mapped. Paired aortic wall samples (from same-patient with elevated WSS paired to normal WSS regions) were collected during surgery and compared using histology (pentachrome), biomechanics (biaxial mechanical testing), and ECM regulation (protein expression). Patient mean age: 49±18 years; mean aortic diameter: 4.6±0.7cm (range: 3.6 - 6.3cm); 55% had R+L fusion pattern; 36% had severe aortic stenosis. All patients had heterogeneous WSS patterns with regions of elevated WSS adjacent to those of normal WSS. By histology, regions of increased WSS showed greater medial elastin fragmentation, fibrosis, and cystic medial necrosis compared to adjacent areas of normal WSS. Regions of increased WSS showed increased elastic modulus (fold change±SD: 1.53±0.68; P=0.06, N=5) and collagen stiffness (1.37±0.49; P=0.07, N=5) compared to normal WSS regions suggesting altered distensibility. Multiplex protein analyses of ECM regulatory molecules revealed an increase in transforming growth factor β-1 (1.49±0.71, P=0.02), MMP-1 (1.62±0.84; P=0.01), MMP-2 (1.49±1.00; P=0.06), MMP-3 (1.23±0.36; P=0.02), MMP-7 (1.57±0.75; P=0.02), and TIMP-2 (1.26±0.33; P=0.01) in elevated WSS regions suggesting ECM dysregulation consistent with aortic remodeling. Conclusions: In BAV aorta, regional WSS corresponds with local histologic abnormalities, altered biomechanics, and ECM dysregulation. These novel data strongly implicate local hemodynamics as a mediator of BAV aortopathy. With further validation, 4D flow MRI could be used to guide personalized resection strategies.

scholarly journals Augmentation of Wall Shear Stress Inhibits Neointimal Hyperplasia After Stent Implantation

Circulation ◽  
2003 ◽  
Vol 107 (21) ◽  
pp. 2741-2746 ◽  
Author(s):  
Stéphane G. Carlier ◽  
Luc C.A. van Damme ◽  
Casper P. Blommerde ◽  
Jolanda J. Wentzel ◽  
Glenn van Langehove ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Stent Implantation ◽  
Neointimal Hyperplasia ◽  
Wall Shear

A cohort study showing correspondence of low wall shear stress and cephalic arch stenosis in brachiocephalic arteriovenous fistula access

2020 ◽  
pp. 112972982094204
Author(s):  
Mary Hammes ◽  
Kevin Cassel ◽  
Michael Boghosian ◽  
Sydeaka Watson ◽  
Brian Funaki ◽  
...  
Keyword(s):  
Shear Stress ◽  
Cohort Study ◽  
Wall Shear Stress ◽  
Arteriovenous Fistula ◽  
Neointimal Hyperplasia ◽  
Age Group ◽  
Wall Shear ◽  
The Relationship ◽  
Fistula Maturation ◽  
Brachiocephalic Fistula

Background: A brachiocephalic fistula is frequently placed for hemodialysis; unfortunately, cephalic arch stenosis commonly develops, leading to failure. We hypothesized that a contribution to brachiocephalic fistula failure is low wall shear stress resulting in neointimal hyperplasia leading to venous stenosis. The objective of this investigation is to determine correspondence of low wall shear stress and the development of cephalic arch stenosis. Methods: Forty subjects receiving hemodialysis with a primary brachiocephalic fistula access were followed from time of placement for 3 years or until cephalic arch stenosis. Venogram, Doppler, and viscosity were performed at time of fistula maturation, annually for 3 years or to time of cephalic arch stenosis. Computational hemodynamics modeling was performed to determine location and percent low wall shear stress in the arch. The relationship between wall shear stress at time of maturation and location of cephalic arch stenosis were estimated by correlating computational modeling and quadrant location of cephalic arch stenosis. Results: In total, 32 subjects developed cephalic arch stenosis with 26 displaying correspondence between location of low wall shear stress at time of maturation and subsequent cephalic arch stenosis, whereas 6 subjects did not (p = 0.0015). Most subjects with correspondence had low wall shear stress areas evident in greater than 20% of the arch (p = 0.0006). Low wall shear stress was associated with a higher risk of cephalic arch stenosis in the 23-to-45 age group (p = 0.0029). Conclusions: The presence and magnitude of low wall shear stress in the cephalic arch is a factor associated with development of cephalic arch stenosis in patients with brachiocephalic fistula. Attenuation of low wall shear stress at time of maturation may help prevent the development of cephalic arch stenosis which is difficult to treat once it develops.

scholarly journals Adventitial delivery of nanoparticles encapsulated with 1α, 25-dihydroxyvitamin D3 attenuates restenosis in a murine angioplasty model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chuanqi Cai ◽  
Sreenivasulu Kilari ◽  
Chenglei Zhao ◽  
Avishek K. Singh ◽  
Michael L. Simeon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Neointimal Hyperplasia ◽  
Immunohistochemical Analysis ◽  
Early Response ◽  
Pluronic F127 ◽  
Dihydroxyvitamin D ◽  
Venous Stenosis ◽  
Wall Shear

AbstractPercutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVFs) is performed to maintain optimal function and patency. The one-year patency rate is 60% because of venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation. Immediate early response gene X-1 (Iex-1) also known as Ier3 increases in response to wall shear stress (WSS), and can cause VNH/VS formation in murine AVF. In human stenotic samples from AVFs, we demonstrated increased gene expression of Ier3. We hypothesized that 1α, 25-dihydroxyvitamin D3, an inhibitor of IER3 delivered as 1α, 25-dihydroxyvitamin D3 encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles loaded in Pluronic F127 hydrogel (1,25 NP) to the adventitia of the stenotic outflow vein after PTA would decrease VNH/VS formation by reducing Ier3 and chemokine (C–C motif) ligand 2 (Ccl2) expression. In our murine model of AVF stenosis treated with PTA, increased expression of Ier3 and Ccl2 was observed. Using this model, PTA was performed and 10-μL of 1,25 NP or control vehicle (PLGA in hydrogel) was administered by adventitial delivery. Animals were sacrificed at day 3 for unbiased whole genome transcriptomic analysis and at day 21 for immunohistochemical analysis. Doppler US was performed weekly after AVF creation. At day 3, significantly lower gene expression of Ier3 and Ccl2 was noted in 1,25 NP treated vessels. Twenty-one days after PTA, 1,25 NP treated vessels had increased lumen vessel area, with decreased neointima area/media area ratio and cell density compared to vehicle controls. There was a significant increase in apoptosis, with a reduction in CD68, F4/80, CD45, pro-inflammatory macrophages, fibroblasts, Picrosirius red, Masson’s trichrome, collagen IV, and proliferation accompanied with higher wall shear stress (WSS) and average peak velocity. IER3 staining was localized to CD68 and FSP-1 (+) cells. After 1,25 NP delivery, there was a decrease in the proliferation of α-SMA (+) and CD68 (+) cells with increase in the apoptosis of FSP-1 (+) and CD68 (+) cells compared to vehicle controls. RNA sequencing revealed a decrease in inflammatory and apoptosis pathways following 1,25 NP delivery. These data suggest that adventitial delivery of 1,25 NP reduces VNH and venous stenosis formation after PTA.

Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries

2005 ◽  
Vol 288 (5) ◽  
pp. H2465-H2475 ◽  
Author(s):  
John F. LaDisa ◽  
Lars. E. Olson ◽  
Robert C. Molthen ◽  
Douglas A. Hettrick ◽  
Phillip F. Pratt ◽  
...  
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Iliac Artery ◽  
Stent Implantation ◽  
Neointimal Hyperplasia ◽  
Three Dimensional ◽  
Iliac Arteries ◽  
Wall Shear

Restenosis resulting from neointimal hyperplasia (NH) limits the effectiveness of intravascular stents. Rates of restenosis vary with stent geometry, but whether stents affect spatial and temporal distributions of wall shear stress (WSS) in vivo is unknown. We tested the hypothesis that alterations in spatial WSS after stent implantation predict sites of NH in rabbit iliac arteries. Antegrade iliac artery stent implantation was performed under angiography, and blood flow was measured before casting 14 or 21 days after implantation. Iliac artery blood flow domains were obtained from three-dimensional microfocal X-ray computed tomography imaging and reconstruction of the arterial casts. Indexes of WSS were determined using three-dimensional computational fluid dynamics. Vascular histology was unchanged proximal and distal to the stent. Time-dependent NH was localized within the stented region and was greatest in regions exposed to low WSS and acute elevations in spatial WSS gradients. The lowest values of WSS spatially localized to the stented area of a theoretical artery progressively increased after 14 and 21 days as NH occurred within these regions. This NH abolished spatial disparity in distributions of WSS. The results suggest that stents may introduce spatial alterations in WSS that modulate NH in vivo.

Increase of wall shear stress caused by arteriovenous fistula reduces neointimal hyperplasia after stent implantation in healthy arteries

Vascular ◽  
2020 ◽  
Vol 28 (4) ◽  
pp. 396-404
Author(s):  
Chong Dong Liu ◽  
Feng Chen
Keyword(s):  
Shear Stress ◽  
Carotid Artery ◽  
Wall Shear Stress ◽  
Arteriovenous Fistula ◽  
Common Carotid Artery ◽  
Stent Implantation ◽  
Neointimal Hyperplasia ◽  
Stent Group ◽  
Wall Shear ◽  
Endothelial Nitric Oxide

Background and objectives Wall shear stress plays a critical role in neointimal hyperplasia after stent implantation. It has been found that there is an inverse relation between wall shear stress and neointimal hyperplasia. This study hypothesized that the increase of arterial wall shear stress caused by arteriovenous fistula could reduce neointimal hyperplasia after stents implantation. Methods and results Thirty-six male rabbits were randomly divided into three groups: STENT, rabbits received stent implantation into right common carotid artery; STENT/arteriovenous fistula, rabbits received stent implantation into right common carotid artery and carotid-jugular arteriovenous fistula; Control, rabbits received no treatment. After 21 days, stented common carotid artery specimens were harvested for histological staining and protein expression analysis. In STENT group, wall shear stress maintained at a low level from 43.2 to 48.9% of baseline. In STENT/arteriovenous fistula group, wall shear stress gradually increased to 86% over baseline. There was a more significant neointimal hyperplasia in group STENT compared with the STENT/arteriovenous fistula group (neointima area: 0.87 mm2 versus 0.19 mm2; neointima-to-media area ratio: 1.13 versus 0.18). Western blot analysis demonstrated that the protein level of endothelial nitric oxide synthase in STENT group was significantly lower than that in STENT/arteriovenous fistula group, but the protein levels of proliferating cell nuclear antigen, vascular cell adhesion molecule 1, phospho-p38 mitogen-activated protein kinase (Pp38), and phospho-c-Jun N-terminal kinase in STENT group were significantly higher than that in the STENT group. Conclusion High wall shear stress caused by arteriovenous fistula as associated with the induction in neointimal hyperplasia after stent implantation. The underlying mechanisms may be related to modulating the expression and activation of endothelial nitric oxide synthase, vascular cell adhesion molecule 1, p38, and c-Jun N-terminal kinase.

scholarly journals Stent design properties and deployment ratio influence indexes of wall shear stress: a three-dimensional computational fluid dynamics investigation within a normal artery

2004 ◽  
Vol 97 (1) ◽  
pp. 424-430 ◽  
Author(s):  
John F. LaDisa ◽  
Lars E. Olson ◽  
Ismail Guler ◽  
Douglas A. Hettrick ◽  
Said H. Audi ◽  
...  
Keyword(s):  
Fluid Dynamics ◽  
Computational Fluid Dynamics ◽  
Shear Stress ◽  
Wall Shear Stress ◽  
Neointimal Hyperplasia ◽  
Three Dimensional ◽  
Vascular Anatomy ◽  
Fold Increase ◽  
Stent Strut ◽  
Wall Shear

Restenosis limits the effectiveness of stents, but the mechanisms responsible for this phenomenon remain incompletely described. Stent geometry and expansion during deployment produce alterations in vascular anatomy that may adversely affect wall shear stress (WSS) and correlate with neointimal hyperplasia. These considerations have been neglected in previous computational fluid dynamics models of stent hemodynamics. Thus we tested the hypothesis that deployment diameter and stent strut properties (e.g., number, width, and thickness) influence indexes of WSS predicted with three-dimensional computational fluid dynamics. Simulations were based on canine coronary artery diameter measurements. Stent-to-artery ratios of 1.1 or 1.2:1 were modeled, and computational vessels containing four or eight struts of two widths (0.197 or 0.329 mm) and two thicknesses (0.096 or 0.056 mm) subjected to an inlet velocity of 0.105 m/s were examined. WSS and spatial WSS gradients were calculated and expressed as a percentage of the stent and vessel area. Reducing strut thickness caused regions subjected to low WSS (<5 dyn/cm2) to decrease by ∼87%. Increasing the number of struts produced a 2.75-fold increase in exposure to low WSS. Reducing strut width also caused a modest increase in the area of the vessel experiencing low WSS. Use of a 1.2:1 deployment ratio increased exposure to low WSS by 12-fold compared with stents implanted in a 1.1:1 stent-to-vessel ratio. Thinner struts caused a modest reduction in the area of the vessel subjected to elevated WSS gradients, but values were similar for the other simulations. The results suggest that stent designs that reduce strut number and thickness are less likely to subject the vessel to distributions of WSS associated with neointimal hyperplasia.

scholarly journals Stent implantation alters coronary artery hemodynamics and wall shear stress during maximal vasodilation

2002 ◽  
Vol 93 (6) ◽  
pp. 1939-1946 ◽  
Author(s):  
John F. LaDisa ◽  
Douglas A. Hettrick ◽  
Lars E. Olson ◽  
Ismail Guler ◽  
Eric R. Gross ◽  
...  
Keyword(s):  
Fluid Dynamics ◽  
Blood Flow ◽  
Shear Stress ◽  
Coronary Artery ◽  
Wall Shear Stress ◽  
Vascular Resistance ◽  
Stent Implantation ◽  
Oscillatory Shear ◽  
Wall Shear ◽  
Oscillatory Shear Stress

Coronary stents improve resting blood flow and flow reserve in the presence of stenoses, but the impact of these devices on fluid dynamics during profound vasodilation is largely unknown. We tested the hypothesis that stent implantation affects adenosine-induced alterations in coronary hemodynamics and wall shear stress in anesthetized dogs ( n = 6) instrumented for measurement of left anterior descending coronary artery (LAD) blood flow, velocity, diameter, and radius of curvature. Indexes of fluid dynamics and shear stress were determined before and after placement of a slotted-tube stent in the absence and presence of an adenosine infusion (1.0 mg/min). Adenosine increased blood flow, Reynolds (Re) and Dean numbers (De), and regional and oscillatory shear stress concomitant with reductions in LAD vascular resistance and segmental compliance before stent implantation. Increases in LAD blood flow, Re, De, and indexes of shear stress were observed after stent deployment ( P < 0.05). Stent implantation reduced LAD segmental compliance to zero and potentiated increases in segmental and coronary vascular resistance during adenosine. Adenosine-induced increases in coronary blood flow and reserve, Re, De, and regional and oscillatory shear stress were attenuated after the stent was implanted. The results indicate that stent implantation blunts alterations in fluid dynamics during coronary vasodilation in vivo.

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

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Pengfei Liu ◽  
Xiaoyan Deng ◽  
Xiao Liu ◽  
Anqiang Sun ◽  
Hongyan Kang
Keyword(s):  
Shear Stress ◽  
Wall Shear Stress ◽  
Stent Implantation ◽  
Neointimal Hyperplasia ◽  
Flow Analysis ◽  
Stent Restenosis ◽  
Relative Residence Time ◽  
Hemodynamic State ◽  
Wall Shear ◽  
In Stent Restenosis

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.

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