Neutrophil Adhesion on Endothelial Cells in a Novel Asymmetric Stenosis Model: Effect of Wall Shear Stress Gradients

Rouleau, Léonie; Copland, Ian B.; Tardif, Jean‐Claude; Mongrain, Rosaire; Leask, Richard L.

doi:10.1007/s10439-010-0032-4

Cited by 34 publications

(31 citation statements)

References 56 publications

(60 reference statements)

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“…This prediction is consistent with the experimental findings by others [42,43]. Cicha et al [42] found that the disturbed flow at the outer wall of an arterial bifurcation could downregulate the expression of eNOS and hence reduce the release of NO, leading to enhanced monocyte recruitment.…”

Section: Discussionsupporting

confidence: 92%

Nitric oxide transport in an axisymmetric stenosis

Liu

Fan

et al. 2012

J. R. Soc. Interface.

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To test the hypothesis that disturbed flow can impede the transport of nitric oxide (NO) in the artery and hence induce atherogenesis, we used a lumen -wall model of an idealized arterial stenosis with NO produced at the blood vessel -wall interface to study the transport of NO in the stenosis. Blood flows in the lumen and through the arterial wall were simulated by Navier -Stokes equations and Darcy's Law, respectively. Meanwhile, the transport of NO in the lumen and the transport of NO within the arterial wall were modelled by advection -diffusion reaction equations. Coupling of fluid dynamics at the endothelium was achieved by the Kedem -Katchalsky equations. The results showed that both the hydraulic conductivity of the endothelium and the non-Newtonian viscous behaviour of blood had little effect on the distribution of NO. However, the blood flow rate, stenosis severity, red blood cells (RBCs), RBC-free layer and NO production rate at the blood vessel -wall interface could significantly affect the transport of NO. The theoretical study revealed that the transport of NO was significantly hindered in the disturbed flow region distal to the stenosis. The reduced NO concentration in the disturbed flow region might play an important role in the localized genesis and development of atherosclerosis.

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Section: Discussionsupporting

confidence: 92%

Nitric oxide transport in an axisymmetric stenosis

Liu

Fan

et al. 2012

J. R. Soc. Interface.

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“…These cells have been shown to have a number of markers of the granulocytic lineage and increased expression of α4 (VLA4) and β2 (LFA-1, Mac-1) [54,55]. We have previously shown the utility of these cells in identifying regional variations in leukocyte attachment [34]. The glycocalyx in vivo is considerably thicker than that measured in vitro [56].…”

Section: Discussionmentioning

confidence: 99%

Glycocalyx Degradation Induces a Proinflammatory Phenotype and Increased Leukocyte Adhesion in Cultured Endothelial Cells under Flow

et al. 2016

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Leukocyte adhesion to the endothelium is an early step in the pathogenesis of atherosclerosis. Effective adhesion requires the binding of leukocytes to their cognate receptors on the surface of endothelial cells. The glycocalyx covers the surface of endothelial cells and is important in the mechanotransduction of shear stress. This study aimed to identify the molecular mechanisms underlying the role of the glycocalyx in leukocyte adhesion under flow. We performed experiments using 3-D cell culture models, exposing human abdominal aortic endothelial cells to steady laminar shear stress (10 dynes/cm2 for 24 hours). We found that with the enzymatic degradation of the glycocalyx, endothelial cells developed a proinflammatory phenotype when exposed to uniform steady shear stress leading to an increase in leukocyte adhesion. Our results show an up-regulation of ICAM-1 with degradation compared to non-degraded controls (3-fold increase, p<0.05) and we attribute this effect to a de-regulation in NF-κB activity in response to flow. These results suggest that the glycocalyx is not solely a physical barrier to adhesion but rather plays an important role in governing the phenotype of endothelial cells, a key determinant in leukocyte adhesion. We provide evidence for how the destabilization of this structure may be an early and defining feature in the initiation of atherosclerosis.

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“…The Reynold's number was maintained well under 2000 and theoretical entrance length calculations were done to ensure that the flow was fully developed. Previous work by our group has validated the developed nature of the flow using photochromic molecular flow visualization in the tubular cell culture models (Rouleau et al 2010a). Confluent HAAEC were pre-conditioned with steady laminar flow (LSS = 1.25, 12.5 or 25 dynes/cm 2 ) for 6 h in growth medium.…”

Section: Flow Experimentsmentioning

confidence: 96%