Augmentation of Wall Shear Stress Inhibits Neointimal Hyperplasia After Stent Implantation

Carlier, Stéphane; Damme, Luc C.A. van; Blommerde, Casper P.; Wentzel, Jolanda J.; Langehove, Glenn van; Verheye, Stephan; Kockx, Mark; Knaapen, Michiel; Cheng, Caroline; Gijsen, Frank; Duncker, Dirk J.; Stergiopulos, Nikolaos; Slager, Cornelis J.; Serruys, Patrick W.; Krams, Rob

doi:10.1161/01.cir.0000066914.95878.6d

Cited by 98 publications

(65 citation statements)

References 20 publications

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“…Following coronary stent deployment, sites of aggressive neointimal hyperplasia also correspond to sites subjected to non-physiological flow conditions, and this has been attributed to increased endothelial dysfunction and permeability. 6,17,18,20,21,52,71,79,88 The hemodynamic impact of the investigated stents was evaluated in terms of the relative residence time distribution predicted upon the lumen surface during the third cardiac cycle. The RRT accounts for temporal variations in both the magnitude and the orientation of the instantaneous wall shear stress vector and is calculated as follows:…”

Section: Analysis Of Balloon-expandable Coronary Stentsmentioning

confidence: 99%

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Sequential Structural and Fluid Dynamics Analysis of Balloon-Expandable Coronary Stents: A Multivariable Statistical Analysis

Martín¹,

Boyle²

2015

Cardiovasc Eng Tech

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Abstract-Several clinical studies have identified a strong correlation between neointimal hyperplasia following coronary stent deployment and both stent-induced arterial injury and altered vessel hemodynamics. As such, the sequential structural and fluid dynamics analysis of balloon-expandable stent deployment should provide a comprehensive indication of stent performance. Despite this observation, very few numerical studies of balloon-expandable coronary stents have considered both the mechanical and hemodynamic impact of stent deployment. Furthermore, in the few studies that have considered both phenomena, only a small number of stents have been considered. In this study, a sequential structural and fluid dynamics analysis methodology was employed to compare both the mechanical and hemodynamic impact of six balloon-expandable coronary stents. To investigate the relationship between stent design and performance, several common stent design properties were then identified and the dependence between these properties and both the mechanical and hemodynamic variables of interest was evaluated using statistical measures of correlation. Following the completion of the numerical analyses, stent strut thickness was identified as the only common design property that demonstrated a strong dependence with either the mean equivalent stress predicted in the artery wall or the mean relative residence time predicted on the luminal surface of the artery. These results corroborate the findings of the large-scale ISAR-STEREO clinical studies and highlight the crucial role of strut thickness in coronary stent design. The sequential structural and fluid dynamics analysis methodology and the multivariable statistical treatment of the results described in this study should prove useful in the design of future balloon-expandable coronary stents.

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Section: Analysis Of Balloon-expandable Coronary Stentsmentioning

confidence: 99%

“…6,17,18,20,21,52,71,79,88 In light of these observations, a significant body of research has been carried out in this area. Due to the difficulty involved in the evaluation of these phenomena in an in vivo setting however, a large portion of this research has been carried out using computational methods of analysis.…”

Section: Introductionmentioning

confidence: 99%

Sequential Structural and Fluid Dynamics Analysis of Balloon-Expandable Coronary Stents: A Multivariable Statistical Analysis

Martín¹,

Boyle²

2015

Cardiovasc Eng Tech

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“…[1][2][3][4][5][6][7] Increases in arterial wall shear stress prevent vascular remodeling leading to thickening of the vascular wall and inflammation, 2 whereas decreases in arterial wall shear stress promote arterial remodeling and inflammation. 2,3 Additionally, low wall shear stress leads to degradation of the internal elastic lamina (IEL). 5 Despite these findings, the underlying mechanisms by which shear regulates proteases degrading vessel wall matrix and IEL are not well described.…”

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confidence: 99%

Laminar shear stress inhibits cathepsin L activity in endothelial cells

Platt

Ankeny

2006

Vascular Pharmacology

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Objective-The cysteine proteases, cathepsins, have been implicated in vascular remodeling and atherosclerosis, processes known to be regulated by shear stress. It is not known, however, whether shear regulates cathepsins. We examined the hypothesis that shear stress regulates cathepsin activity in endothelial cells. Methods and Results-Mouse aortic endothelial cells (MAECs) exposed to atheroprotective, unidirectional laminar shear (LS) degraded significantly less BODIPY-labeled elastin and gelatin in comparison to static and proatherogenic oscillatory shear (OS). The cathepsin inhibitor E64 also reduced this activity. Gelatin zymography showed that cathepsin activity of MAECs was blunted by LS exposure and by a cathepsin L inhibitor but not by cathepsin B and S inhibitors, whereas a cathepsin K inhibitor had a minor effect. Cathepsin L siRNA knocked down cathepsin L expression, gelatinase, and elastase activity in OS and static MAECs. A partial reduction of cathepsin B protein raised the possibility that the siRNA effect on the matrix protease activity could have been attributable to cathepsin L or B. Cathepsin B activity study using the synthetic peptide showed it was not regulated by shear. Key Words: shear stress Ⅲ cathepsin Ⅲ elastase Ⅲ gelatinase Ⅲ atherosclerosis V ascular endothelial cells are constantly exposed to fluid shear stress, the frictional force generated by blood flow over the vascular endothelium. The importance of shear stress in vascular biology and pathophysiology has been highlighted by the focal development patterns of atherosclerosis in hemodynamically defined regions. For example, the regions of branched and curved arteries exposed to disturbed flow conditions including oscillatory and low mean shear stresses (OS) correspond to atheroprone areas. In contrast, straight arteries exposed to pulsatile high levels of laminar shear stress (LS) are relatively well protected from atherosclerotic plaque development. 1 Changes in blood flow have been shown to be a critical factor inducing arterial remodeling. 1-7 Increases in arterial wall shear stress prevent vascular remodeling leading to thickening of the vascular wall and inflammation, 2 whereas decreases in arterial wall shear stress promote arterial remodeling and inflammation. 2,3 Additionally, low wall shear stress leads to degradation of the internal elastic lamina (IEL). 5 Despite these findings, the underlying mechanisms by which shear regulates proteases degrading vessel wall matrix and IEL are not well described. Although there is a report demonstrating that shear regulates matrix metalloproteases (MMPs) in endothelial cells, 8 it is not clear whether other proteases are also regulated by shear. Conclusions-TheseCathepsins are the papain family of cysteine proteases which degrade elastin in addition to collagen. 9 Unlike MMPs, the role for cathepsins in blood vessel remodeling and cardiovascular disease has been understudied until recently. Cathepsins K, L, and S, potent elastinolytic proteases, have been identified in atheroscleroti...

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“…Thus, a low shear stress could lead to reduction of the cross-sectional area of renal ostium owing to presence of stent wires (because of formation of neointimal hyperplasia on the stent surface). It has been reported that augmentation of wall shear stress is accompanied by a local reduction in neointimal hyperplasia [21]. Another potential risk of a low shear stress is the formation of artery plaque or atherosclerosis in the aortic branches [22].…”

Section: Discussionmentioning

confidence: 99%

Investigation of the Hemodynamic Effect of Stent Wires on Renal Arteries in Patients with Abdominal Aortic Aneurysms Treated with Suprarenal Stent-Grafts

Sun

Chaichana

2009

Cardiovasc Intervent Radiol

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Investigation of hemodynamic effect of stent wires on renal arteries in patients with abdominal aortic aneurysms treated with suprarenal stent grafts 2 Abstract Purpose: The purpose of the study was to investigate the hemodynamic effect of stent struts (wires) on renal arteries in patients with abdominal aortic aneurysms (AAA) treated with suprarenal stent grafts. Materials and Methods:Two sample patients with AAA undergoing multislice CT angiography pre-and post-suprarenal fixation of stent grafts were selected for inclusion in the study. Eight juxtarenal models focusing on the renal arteries were generated from the multislice CT datasets. Four types of configurations of stent wires crossing the renal artery ostium, namely single wire centrally crossing, single wire peripherally crossing, Vshaped wire centrally crossing and multiple wires peripherally crossing were simulated in the segmented aorta models. The blood flow pattern, flow velocity, wall pressure and wall shear stress at the renal arteries pre-and post-stent grafting were analyzed and compared using a two-way fluid structure interaction analysis. The stent wire thickness was simulated with a diameter of 0.4 mm, 1.0 mm and 2.0 mm, and hemodynamic analysis was performed at different cardiac cycles. Results:The interference of stent wires with renal blood flow was mainly determined by the thickness of stent wires, and the type of configuration of stent wires crossing the renal ostium. The flow velocity was reduced by 20-30% in most of the situations when the stent wire thickness increased to 1.0 mm and 2.0 mm. Of 4 types of configuration, the single wire crossing centrally resulted in the highest reduction of flow velocity, ranging from 21% to 28.9% among three different wire thicknesses. Wall shear stress was also dependent on the wire thickness, which decreased significantly when the wire thickness reached 1.0 and 2.0 mm.3 Conclusion: Our preliminary study showed that the hemodynamic effect of suprarenal stent wires in patients with AAA treated with suprarenal stent grafts was determined by the thickness of suprarenal stent wires. Research findings in our study are useful for follow-up of patients treated with suprarenal stent grafts to ensure long-term safety of the suprarenal fixation.

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Augmentation of Wall Shear Stress Inhibits Neointimal Hyperplasia After Stent Implantation

Cited by 98 publications

References 20 publications

Sequential Structural and Fluid Dynamics Analysis of Balloon-Expandable Coronary Stents: A Multivariable Statistical Analysis

Sequential Structural and Fluid Dynamics Analysis of Balloon-Expandable Coronary Stents: A Multivariable Statistical Analysis

Laminar shear stress inhibits cathepsin L activity in endothelial cells

Investigation of the Hemodynamic Effect of Stent Wires on Renal Arteries in Patients with Abdominal Aortic Aneurysms Treated with Suprarenal Stent-Grafts

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