Influence of Oscillatory and Unidirectional Flow Environments on the Expression of Endothelin and Nitric Oxide Synthase in Cultured Endothelial Cells

Ziegler, Thierry; Bouzourène, Karima; Harrison, Vanessa J.; Brunner, Hans R.; Hayoz, Daniel

doi:10.1161/01.atv.18.5.686

Cited by 296 publications

(234 citation statements)

References 29 publications

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“…A reduced accumulation of macrophages may be a result of reduced expression of vascular cell adhesion molecule-1 or monocyte chemotactic protein-1 or an increased NO production. 16,17 The present data imply that high shear stress is protective against NH, which is in accordance with a recent study in human coronary arteries by Wentzel et al 3 …”

supporting

confidence: 93%

Augmentation of Wall Shear Stress Inhibits Neointimal Hyperplasia After Stent Implantation

Carlier¹,

Damme²,

Blommerde³

et al. 2003

Circulation

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Background-Low wall shear stress (WSS) increases neointimal hyperplasia (NH) in vein grafts and stents. We studied the causal relationship between WSS and NH formation in stents by locally increasing WSS with a flow divider (Anti-Restenotic Diffuser, Endoart SA) placed in the center of the stent. Methods and Results-In 9 rabbits fed a high-cholesterol diet for 2 months to induce endothelial dysfunction, 18 stents were implanted in the right and left external iliac arteries (1 stent per vessel). Lumen diameters were measured by quantitative angiography before and after implantation and at 4-week follow-up, at which time, macrophage accumulation and interruption of the internal elastic lamina was determined. Cross sections of stent segments within the ARED (SϩARED), outside the ARED (S[minus]ARED), and in corresponding segments of the contralateral control stent (SCTRL) were analyzed. Changes in WSS induced by the ARED placement were derived by computational fluid dynamics. Computational fluid dynamics analysis demonstrated that WSS increased from 0.38 to 0.82 N/m 2 in the SϩARED immediately after ARED placement. This augmentation of shear stress was accompanied by (1) ARED, and SCTRL), and (3) a reduced inflammation score and a reduced injury score. Increments in shear stress did not change the relationship between injury score and NH or between inflammation score and NH. Conclusions-The newly developed ARED flow divider significantly increases WSS, and this local increment in WSS isaccompanied by a local reduction in NH and a local reduction in inflammation and injury. The present study is therefore the first to provide direct evidence for an important modulating role of shear stress in in-stent neointimal hyperplasia. Key Words: shear stress Ⅲ restenosis Ⅲ stents Ⅲ cells Ⅲ inflammation A lthough stents are responsible for a clear reduction in the restenosis rate, 1 stents exacerbate the normal proliferative reaction because of a variety of factors related to stent design. 2 In addition to conventional risk factors for stent restenosis, the restored level of blood flow seems to be a crucial factor in the development of neointimal hyperplasia (NH). 3 It has been postulated that wall shear stress (WSS) is an important causative factor. Indeed, other studies 4 have demonstrated that low WSS is associated with and even predicts NH in either bypass graft or stents. However, these earlier studies could not exclude the possibility that other factors in addition to WSS explained the observations. This hypothesis is not unrealistic, because it is known that the strain and lipid distribution are different in inner and outer curves of blood vessels. 5,6 In view of the above-mentioned arguments, we devised an experiment to evaluate the role of shear stress on NH with a more direct approach. To that end, we induced a local augmentation in WSS with a new device, the AntiRestenotic Diffuser (ARED) flow divider (Figure 1; European patent number EP0989830), which is positioned in 1 of the 2 stents placed at similar locations in...

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supporting

confidence: 93%

Augmentation of Wall Shear Stress Inhibits Neointimal Hyperplasia After Stent Implantation

Carlier¹,

Damme²,

Blommerde³

et al. 2003

Circulation

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“…5). Although higher levels of shear stress can stimulate gene expression (26) and affect cell differentiation pathways (27), the levels we predict in our system are very low compared with those reported to induce gene or protein expression in endothelial cells (28,29). Thus, it is unlikely that shear-induced mechanotransduction is the primary mechanism responsible for the significant change in the networking effects observed.…”

Section: Mechanisms Of Synergy: Shear Stress Versus Directionally Biamentioning

confidence: 53%

Synergy between interstitial flow and VEGF directs capillary morphogenesisin vitrothrough a gradient amplification mechanism

Helm

Fleury

Zisch

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

256

240

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Cell organization is largely orchestrated by extracellular gradients of morphogenetic proteins. VEGF, an essential factor for capillary formation, is stored in the extracellular matrix, but the mechanisms by which it and other matrix-bound morphogens are mobilized to form spatial gradients are poorly understood. Here, we suggest an efficient mechanism for morphogen gradient generation by subtle biophysical forces in an in vitro model of capillary morphogenesis. Using a fibrin-bound VEGF variant that is released proteolytically to mimic the in vivo situation, we report that low levels of interstitial flow act synergistically with VEGF to drive endothelial organization, whereas each stimulus alone has very little effect. To help account for this synergy, we show how these slow flows can bias the distribution of cell-secreted proteases, which leads, interestingly, to the creation of an increasing VEGF gradient relative to the cell and skewed in the direction of flow. In contrast, diffusion alone can only account for symmetric, decreasing autocrine gradients. Indeed, branching of capillary structures was biased in the direction of flow only with the combination of VEGF and flow. This work thus demonstrates a general mechanism of morphogen gradient generation and amplification by small ubiquitous mechanical forces that are known to exist in vivo.fibrin ͉ angiogenesis ͉ lymphatic ͉ biotransport ͉ mechanobiology T issue morphogenesis results from the organization of cells into functional structures by means of the actions of biomolecular morphogens. The efficacy of a morphogen depends largely on its local gradient relative to the cell rather than its absolute amount (1). Such morphogens, particularly growth factors and some cytokines, commonly bind to the extracellular matrix (ECM) to be later released by cells via proteolytic enzymes. Although Alan Turing (2) first showed how patterns in morphogenesis could arise from diffusion and interaction kinetics, his arguments were derived for directly cell-secreted morphogens. The question of how cells create morphogen gradients by proteolytically mobilizing matrix-bound factors has not yet been addressed, and we wondered whether small biophysical forces that are ubiquitously present in vivo may help facilitate cell utilization of such factors.

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“…Site oscillatory shear stress may contribute to endothelial dysfunction by inducing increased Endothelin-1 and decreased NO production, thus leading to cellular toxicity. 22 Oscillatory shear stress and cyclic strain increase vascular oxidative stress and enhance the vascular production of reactive oxygen species, which impairs endotheliumdependent vasodilation, NO bioavailability, and anti-inflammatory response. 23,24 During the augmented beats, the increased mean WSS reversal and oscillatory components would have shifted the relaxing/activating endothelial factor equilibrium, increasing the basal or resting VSM tone.…”

Section: Osimentioning

confidence: 99%

Influence of Hemodynamic Factors on Rupture of Intracranial Aneurysms: Patient-Specific 3D Mirror Aneurysms Model Computational Fluid Dynamics Simulation

Lü¹,

Huang²,

Zhang³

et al. 2011

AJNR Am J Neuroradiol

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Influence of Oscillatory and Unidirectional Flow Environments on the Expression of Endothelin and Nitric Oxide Synthase in Cultured Endothelial Cells

Cited by 296 publications

References 29 publications

Augmentation of Wall Shear Stress Inhibits Neointimal Hyperplasia After Stent Implantation

Augmentation of Wall Shear Stress Inhibits Neointimal Hyperplasia After Stent Implantation

Synergy between interstitial flow and VEGF directs capillary morphogenesisin vitrothrough a gradient amplification mechanism

Influence of Hemodynamic Factors on Rupture of Intracranial Aneurysms: Patient-Specific 3D Mirror Aneurysms Model Computational Fluid Dynamics Simulation

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