Effect of carotid artery geometry on the magnitude and distribution of wall shear stress gradients

Wells, Don R.; Archie, Joseph P.; Kleinstreuer, Clement

doi:10.1016/s0741-5214(96)80048-6

Cited by 85 publications

(49 citation statements)

References 26 publications

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“…The potential roles of high-versus low-shear stress gradients in vascular biology are flow patterns in the lesion-prone areas that are disturbed by high spatial and temporal shear stress gradients and flow patterns in lesionresistant areas being steady laminar flows with low-shear stress gradients. 30,31 Thus, our study supports the hypothesis that the focal distribution of lipids in the arterial tree is due in part to local flow patterns.…”

Section: Discussionsupporting

confidence: 84%

Shear Stress Activation of SREBP1 in Endothelial Cells Is Mediated by Integrins

Liu

Chen

Lü

et al. 2002

ATVB

128

106

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Abstract-We investigated the effect of shear stress on the sterol regulatory element-binding protein 1 (SREBP1) in vascular endothelial cells (ECs) and the mechanotransduction mechanism involved. Application of a shear stress (12 dyn/cm 2 ) caused the proteolytic cleavage of SREBP1 and the ensuing translocation of its transcription factor domain into the nucleus. As a result, shear stress increased the mRNAs encoding the low density lipoprotein receptor (LDLR), as well as the binding of 125 I-LDL. Using a step flow channel, we showed that SREBP1 activation in ECs under laminar flow is transient, but disturbed flow causes sustained activation. In studying the shear stress-elicited molecular signaling that activates SREBP1, we found that blocking the ␤ 1 -integrin with the AIIB2 blocking-type monoclonal antibody inhibited SREBP1 activation induced by shear stress. EC attachment to fibronectin or the activation of ␤ 1 -integrin in the suspended ECs by the TS2/16 monoclonal antibody was sufficient for SREBP1 activation. Furthermore, transient transfection assays showed that dominant-negative mutants of focal adhesion kinase and c-Src attenuated the shear stress-increased LDLR promoter activity. These results demonstrate that integrin signaling plays a critical role in the modulation of SREBP in ECs in response to shear stress. Key Words: shear stress Ⅲ sterol regulatory element-binding protein 1 Ⅲ integrins Ⅲ endothelial cells Ⅲ cholesterol A key feature of atherosclerosis is lipid accumulation in the artery wall resulting from the transendothelial entry of LDL, followed by LDL oxidation and uptake by monocytes/macrophages. 1 Although every part of the arterial tree is exposed to the same concentration of plasma LDL, atherosclerotic lesions are prevalent in bifurcations and curved regions, 2 which suggests that local hemodynamic forces play a significant role in the focal nature of the lesions. 3 This thesis is supported by studies demonstrating that LDL infused into experimental animals is preferentially located in the areas with disturbed blood flow, such as branch points. 4 The increased LDL uptake in the lesion-prone areas can be due to an enhanced permeability through endothelial junctions 5 and/or an LDL receptor (LDLR)-mediated endocytosis. 6 Using an in vitro flow system with cultured vascular endothelial cells (ECs), Sprague et al 7 demonstrated that laminar shear stress increased the binding, internalization, and degradation of LDL in ECs, and these changes were mediated through upregulated LDLR. To date, the molecular mechanism by which shear stress modulates the expression of LDLR has not been elucidated.Sterol regulatory element-binding proteins (SREBPs) are key transcription factors that modulate the multiple genes involved in the biosynthesis of cholesterol and fatty acids and receptor-mediated LDL uptake. There are 3 members in the SREBP family: SREBP1a and SREBP1c are encoded by the same gene, whereas SREBP2 is from a separate gene (see Brown and Goldstein 8 for a review). When cells are depleted of...

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Section: Discussionsupporting

confidence: 84%

Shear Stress Activation of SREBP1 in Endothelial Cells Is Mediated by Integrins

Liu

Chen

Lü

et al. 2002

ATVB

128

106

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“…To simplify our model, rigid walls and Newtonian blood rheology were assumed, and these are generally considered reasonable approximations for the purposes of predicting WSS patterns to within 15% accuracy (33)(34)(35)(36)(37)(38)(39). However, it has been recently demonstrated that pulse propagation effects induced by vessel distensibility can lead to phase shifts between the proximal CCA and ICA/ECA flow waveforms (40), which might account for our need to apply an ad hoc correction to the measured waveforms to ensure mass conservation at all times.…”

Section: Discussionmentioning

confidence: 99%

Reconstruction of carotid bifurcation hemodynamics and wall thickness using computational fluid dynamics and MRI

Steinman

Thomas

Ladak

et al. 2001

Magnetic Resonance in Med

226

146

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A thorough understanding of the relationship between local hemodynamics and plaque progression has been hindered by an inability to prospectively monitor these factors in vivo in humans. In this study a novel approach for noninvasively reconstructing artery wall thickness and local hemodynamics at the human carotid bifurcation is presented. Three-dimensional (3D) models of the lumen and wall boundaries, from which wall thickness can be measured, were reconstructed from blackblood magnetic resonance imaging (MRI). Along with time-varying inlet/outlet flow rates measured via phase contrast (PC) MRI, the lumen boundary was used as input for computational fluid dynamic (CFD) simulation of the subject-specific flow patterns and wall shear stresses (WSSs). Results from a 59-yearold subject with early, asymptomatic carotid artery disease show good agreement between simulated and measured velocities, and demonstrate a correspondence between wall thickening and low and oscillating shear at the carotid bulb. High shear at the distal internal carotid artery (ICA) was also colocalized with higher WSS; however, a quantitative general relationship between WSS and wall thickness was not found. Similar results were obtained from a 23-year-old normal subject. Wall shear stress (WSS) is widely believed to play a key role in the development and progression of atherosclerotic plaques. Studies comparing human post-mortem distributions of plaque to in vitro fluid dynamic models have perhaps provided the most direct observational evidence for the relationship between WSS and the focal development of atherosclerotic lesions (1-4). The mechanisms by which shear stresses alter endothelial function at the cellular, molecular, and genetic level are also now being elucidated (5). Despite these advances, however, many questions still remain regarding the role of fluid dynamics in the development and progression of atherosclerosis. One reason for this has been the difficulty of identifying and monitoring the relationships between local fluid dynamic factors and plaque development on a subject-specific basis.In principle, both MR and ultrasound imaging can be used to measure wall thickness (a marker for atherosclerotic burden) and blood velocities (from which WSSs are derived) directly. However, difficulties associated with the quantification of blood velocities in regions of complex flow have in the past limited the application of such an "imaging-only" approach to relatively straight sections of the abdominal aorta (6), femoral artery (7), and common carotid artery (8 -10). While these studies were able to confirm an inverse relationship between mean or peak shear and intimal or intima-media thickness, it is not yet possible to use imaging techniques alone to map WSS in the regions of complex flow where plaques are known to localize, such as at the carotid bifurcation. Recent work by Stokholm et al. (11) suggests that WSS from individual slices at the carotid bifurcation itself can be quantified in vivo by sophisticated postprocessing of ph...

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“…4 -7,37 Moreover, the disturbed flow patterns associated with shear stress gradients appear to contribute to the growth of the atherosclerotic plaque. 38 We designed our study with these issues in mind: comparable operative procedures in all arteries, stainless steel Goldblatt clamps to standardize and minimize any potential reaction to the collar material, and application of the equivalent amount of stenosis to produce a uniform alteration of shear stress in all arteries. It is clear from our studies that under these conditions, vWF is not essential for neointimal formation.…”

Section: Discussionmentioning

confidence: 99%

von Willebrand Factor Does Not Influence Atherogenesis in Arteries Subjected to Altered Shear Stress

Nichols

Bellinger²,

Reddick³

et al. 1998

ATVB

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Abstract-The role of von Willebrand factor (vWF) in arterial neointimal formation that develops in arteries with altered shear stress was investigated using normal, heterozygous, and homozygous von Willebrand disease pigs (ie, vWD, or lacking vWF) that were fed normal pig chow. Shear stress was applied to carotid and femoral arteries with a Goldblatt clamp for 14 days, producing a Ն80% stenosis. Neointimal lesion size was measured by computer-assisted morphometry. Expression of proliferative cell nuclear antigen (PCNA) by neointimal and medial cells was used as a relative index of proliferative activity. For shear-stressed arteries, there was no significant difference in the number of smooth muscle cell layers in the lesion, lesion size, and percent of PCNA-positive neointimal or medial cells among normal, heterozygous, and homozygous vWD pigs (PՆ.1, ANOVA

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Effect of carotid artery geometry on the magnitude and distribution of wall shear stress gradients

Cited by 85 publications

References 26 publications

Shear Stress Activation of SREBP1 in Endothelial Cells Is Mediated by Integrins

Shear Stress Activation of SREBP1 in Endothelial Cells Is Mediated by Integrins

Reconstruction of carotid bifurcation hemodynamics and wall thickness using computational fluid dynamics and MRI

von Willebrand Factor Does Not Influence Atherogenesis in Arteries Subjected to Altered Shear Stress

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