Characterization of a Sudden Expansion Flow Chamber to Study the Response of Endothelium to Flow Recirculation

Truskey, George A.; Barber, Kevin M.; Robey, Thomas; Olivier, Lauri A.; Combs, Marty P.

doi:10.1115/1.2796002

Cited by 49 publications

(34 citation statements)

References 33 publications

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“…17 The transient activation of SREBP1 by such a laminar shear stress can be viewed as a response to the step change of shear stress from 0 to 12 dyn/cm 2 , which represents a sharp, temporal gradient of shear stress. 29 With continuous exposure to a constant level of laminar shear stress at 12 dyn/cm 2 , ECs can adapt to the constant flow that no longer has a temporal or spatial gradient of shear stress.…”

Section: Discussionmentioning

confidence: 99%

“…17,18 Disturbed flow was created by a step expansion of the height of the flow channel in a parallel-plate channel. In the flow-reattachment area of the step flow channel, the shear stress was close to zero but the spatial gradient was high, whereas at the downstream laminar flow area the shear stress was high with no spatial gradient.…”

Section: Shear Stress Experimentsmentioning

confidence: 99%

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

Liu

Chen

Lü

et al. 2002

ATVB

129

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: Discussionmentioning

confidence: 99%

Section: Shear Stress Experimentsmentioning

confidence: 99%

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

Liu

Chen

Lü

et al. 2002

ATVB

129

106

View full text Add to dashboard Cite

show abstract

“…1(d)) could be achieved. 30 Assuming that the medium is a steady and incompressible fluid, the velocity distributions of the step flow at different chamber heights of 40 lm (the same height as the microchannels), 200 lm, 400 lm, and 600 lm were simulated at a flow rate of 20 ll/h. The surface and arrow plots of the middle plane in x axis were shown in Figs.…”

Section: Resultsmentioning

confidence: 99%

A microfluidic platform for real-time and in situ monitoring of virus infection process

Zhang

Wang

et al. 2012

Biomicrofluidics

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Microfluidic chip is a promising platform for studying virus behaviors at the cell level. However, only a few chip-based studies on virus infection have been reported. Here, a three-layer microfluidic chip with low shear stress was designed to monitor the infection process of a recombinant Pseudorabies virus (GFP-PrV) in real time and in situ, which could express green fluorescent protein during the genome replication. The infection and proliferation characteristics of GFP-PrV were measured by monitoring the fluorescence intensity of GFP and determining the one-step growth curve. It was found that the infection behaviors of GFP-PrV in the host cells could hardly be influenced by the microenvironment in the microfluidic chip. Furthermore, the results of drug inhibition assays on the microfluidic chip with a tree-like concentration gradient generator showed that one of the infection pathways of GFP-PrV in the host cells was microtubule-dependent. This work established a promising microfluidic platform for the research on virus infection.

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“…11 This assumption is valid when channel height is much less than the flow path width. 12 Chamber design was similar to those used by other investigators 13,14 and has the advantages of minimal volume and well defined flow patterns.…”

Section: Parallel Plate Flow Chambermentioning

confidence: 97%

Assessing acute platelet adhesion on opaque metallic and polymeric biomaterials with fiber optic microscopy

Schaub

Kameneva

Borovetz

et al. 2000

J. Biomed. Mater. Res.

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The degree of platelet adhesion and subsequent thrombus formation is an important measure of biocompatibility for cardiovascular biomaterials. Traditional methods of quantifying platelet adhesion often are limited by the need for direct optical access, limited spatial resolution, or the lack of temporal resolution. We have developed a new imaging system that utilizes fiber optics and fluorescence microscopy for the quantification of platelet adhesion. This fiber optic remote microscope is capable of imaging individual fluorescently labeled platelets in whole blood on opaque surfaces. Using this method, platelet adhesion was quantified on a series of metallic [low-temperature isotropic carbon (LTIC); titanium alloy (Ti); diamond-like carbon (DLC); oxidized titanium alloy (TiO); and polycrystalline diamond (PCD)] and polymeric [woven Dacron (WD)] collagen-impregnated Dacron (HEM), expanded polytetrafluoroethylene (ePTFE), and denucleated ePTFE (dePTFE)] biomaterials designed for use in cardiovascular applications. These materials were perfused with heparinized whole human blood in an in vitro parallel plate flow chamber. Platelet adhesion after 5 min of perfusion ranged from 3.7 +/- 1.0 (dePTFE) to 16.8 +/- 1.5 (WD) platelets/1000 micrometer. The temporal information revealed by these studies provides a comparative measure of the acute thrombogenicity of these materials as well as some insight into their long-term hemocompatibilities. Also studied here were the effects of wall shear rate and axial position on platelet adhesion. A predicted increase in platelet adhesion with increased wall shear rate and a trend toward a decrease in platelet adhesion with increased axial distance was observed with the fiber optic microscope. Future applications for this imaging technique may include the long-term evaluation of thrombosis in blood-contacting devices in vitro and, in animal models, in vivo.

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Characterization of a Sudden Expansion Flow Chamber to Study the Response of Endothelium to Flow Recirculation

Cited by 49 publications

References 33 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

A microfluidic platform for real-time and in situ monitoring of virus infection process

Assessing acute platelet adhesion on opaque metallic and polymeric biomaterials with fiber optic microscopy

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