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Sample records for endothelial shear stress

  1. Vascular mechanobiology: endothelial cell responses to fluid shear stress.

    PubMed

    Ando, Joji; Yamamoto, Kimiko

    2009-11-01

    Endothelial cells (ECs) lining blood vessel walls respond to shear stress, a fluid mechanical force generated by flowing blood, and the EC responses play an important role in the homeostasis of the circulatory system. Abnormal EC responses to shear stress impair various vascular functions and lead to vascular diseases, including hypertension, thrombosis, and atherosclerosis. Bioengineering approaches in which cultured ECs are subjected to shear stress in fluid-dynamically designed flow-loading devices have been widely used to analyze EC responses at the cellular and molecular levels. Remarkable progress has been made, and the results have shown that ECs alter their morphology, function, and gene expression in response to shear stress. Shear stress affects immature cells, as well as mature ECs, and promotes differentiation of bone-marrow-derived endothelial progenitor cells and embryonic stem cells into ECs. Much research has been done on shear stress sensing and signal transduction, and their molecular mechanisms are gradually coming to be understood. However, much remains uncertain, and many candidates have been proposed for shear stress sensors. More extensive studies of vascular mechanobiology should increase our understanding of the molecular basis of the blood-flow-mediated control of vascular functions.

  2. Regulation of endothelial connexin40 expression by shear stress.

    PubMed

    Vorderwülbecke, Bernd J; Maroski, Julian; Fiedorowicz, Katarzyna; Da Silva-Azevedo, Luis; Marki, Alex; Pries, Axel R; Zakrzewicz, Andreas

    2012-01-01

    Endothelial connexin (Cx)40 plays an important role in signal propagation along blood vessel walls, modulating vessel diameter and thereby blood flow. Blood flow, in turn, has been shown to alter endothelial Cx40 expression. However, the timing and shear stress dependence of this relationship have remained unclear, as have the signal transduction pathways involved and the functional implications. Therefore, the aim of this study was to quantify the effects of shear stress on endothelial Cx40 expression, to analyze the role of phosphoinositide 3-kinase (PI3K)/Akt signaling involved, and to assess the possible functional consequences for the adaptation of microvascular networks. First-passage human umbilical vein endothelial cells were exposed to defined shear stress conditions and analyzed for Cx40 using real-time RT-PCR and immunoblot analysis. Shear stress caused long-term induction of Cx40 protein expression, with two short-term mRNA peaks at 4 and 16 h, indicating the dynamic nature of the adaptation process. Maximum shear stress-dependent induction was observed at shear levels between 6 and 10 dyn/cm(2). Simulation of this pattern of shear-dependent Cx expression in a vascular adaptation model of a microvascular network led to an improved fit for the simulated results to experimental measurements. Cx40 expression was greatly reduced by inhibiting PI3K or Akt, with PI3K activity being required for basal Cx40 expression and Akt activity taking part in its shear stress-dependent induction.

  3. Human endothelial cell responses to cardiovascular inspired pulsatile shear stress

    NASA Astrophysics Data System (ADS)

    Watson, Matthew; Baugh, Lauren; Black, Lauren, III; Kemmerling, Erica

    2016-11-01

    It is well established that hemodynamic shear stress regulates blood vessel structure and the development of vascular pathology. This process can be studied via in vitro models of endothelial cell responses to pulsatile shear stress. In this study, a macro-scale cone and plate viscometer was designed to mimic various shear stress waveforms found in the body and apply these stresses to human endothelial cells. The device was actuated by a PID-controlled DC gear-motor. Cells were exposed to 24 hours of pulsatile shear and then imaged and stained to track their morphology and secretions. These measurements were compared with control groups of cells exposed to constant shear and no shear. The results showed that flow pulsatility influenced levels of secreted proteins such as VE-cadherin and neuroregulin IHC. Cell morphology was also influenced by flow pulsatility; in general cells exposed to pulsatile shear stress developed a higher aspect ratio than cells exposed to no flow but a lower aspect ratio than cells exposed to steady flow.

  4. Fluid shear, intercellular stress, and endothelial cell alignment.

    PubMed

    Steward, Robert; Tambe, Dhananjay; Hardin, C Corey; Krishnan, Ramaswamy; Fredberg, Jeffrey J

    2015-04-15

    Endothelial cell alignment along the direction of laminar fluid flow is widely understood to be a defining morphological feature of vascular homeostasis. While the role of associated signaling and structural events have been well studied, associated intercellular stresses under laminar fluid shear have remained ill-defined and the role of these stresses in the alignment process has remained obscure. To fill this gap, we report here the tractions as well as the complete in-plane intercellular stress fields measured within the human umbilical vein endothelial cell (HUVEC) monolayer subjected to a steady laminar fluid shear of 1 Pa. Tractions, intercellular stresses, as well as their time course, heterogeneity, and anisotropy, were measured using monolayer traction microscopy and monolayer stress microscopy. Prior to application of laminar fluid flow, intercellular stresses were largely tensile but fluctuated dramatically in space and in time (317 ± 122 Pa). Within 12 h of the onset of laminar fluid flow, the intercellular stresses decreased substantially but continued to fluctuate dramatically (142 ± 84 Pa). Moreover, tractions and intercellular stresses aligned strongly and promptly (within 1 h) along the direction of fluid flow, whereas the endothelial cell body aligned less strongly and substantially more slowly (12 h). Taken together, these results reveal that steady laminar fluid flow induces prompt reduction in magnitude and alignment of tractions and intercellular stress tensor components followed by the retarded elongation and alignment of the endothelial cell body. Appreciably smaller intercellular stresses supported by cell-cell junctions logically favor smaller incidence of gap formation and thus improved barrier integrity.

  5. Sitting and endothelial dysfunction: The role of shear stress

    PubMed Central

    Thosar, Saurabh S.; Johnson, Blair D.; Johnston, Jeanne D.; Wallace, Janet P.

    2012-01-01

    Summary Sedentary activity is a modifiable life-style behavior and a key component in the etiology of atherosclerotic cardiovascular disease (ACVD). US adults and children spend more than half their waking time in sedentary pursuits. Sedentary activity has been shown to result in impaired insulin sensitivity, impaired metabolic function and attenuated endothelial function, which are classic markers of ACVD. Sedentary activity is defined as ‘sitting without otherwise being active.’ This behavior promotes reduced muscular activity of the lower extremities which decreases leg blood flow, increases blood pooling in the calf, augments mean arterial pressure, and deforms arterial segments resulting in low mean shear stress (SS). SS activates distinct physiological mechanisms which have been proposed to be protective against ACVD; specifically through a SS-induced endothelium-derived nitric oxide mechanism. Reduced bioavailability of nitric oxide creates a pro-oxidant milieu resulting in increased oxidative stress. There is sufficient evidence which demonstrates that endothelial function is attenuated in the presence of oxidative stress. Sedentary activity results in low SS in the lower extremities which may result in increased oxidative stress and impaired endothelial function. This review furthers the use of sitting as model to study the effects of inactivity, discusses possible physiological mechanisms and suggests future directions. PMID:23197245

  6. Shear stress activation of nuclear receptor PXR in endothelial detoxification.

    PubMed

    Wang, Xiaohong; Fang, Xi; Zhou, Jing; Chen, Zhen; Zhao, Beilei; Xiao, Lei; Liu, Ao; Li, Yi-Shuan J; Shyy, John Y-J; Guan, Youfei; Chien, Shu; Wang, Nanping

    2013-08-06

    Endothelial cells (ECs) are constantly exposed to xenobiotics and endobiotics or their metabolites, which perturb EC function, as well as to shear stress, which plays a crucial role in vascular homeostasis. Pregnane X receptor (PXR) is a nuclear receptor and a key regulator of the detoxification of xeno- and endobiotics. Here we show that laminar shear stress (LSS), the atheroprotective flow, activates PXR in ECs, whereas oscillatory shear stress, the atheroprone flow, suppresses PXR. LSS activation of PXR in cultured ECs led to the increased expression of a PXR target gene, multidrug resistance 1 (MDR1). An in vivo study using rats showed that the expression of MDR1 was significantly higher in the endothelium from the descending thoracic aorta, where flow is mostly laminar, than from the inner curvature of aortic arch, where flow is disturbed. Functionally, LSS-activated PXR protects ECs from apoptosis triggered by doxorubicin via the induction of MDR1 and other detoxification genes. PXR also suppressed the expression of proinflammatory adhesion molecules and monocyte adhesion in response to TNF-α and lipopolysaccharide. Overexpression of a constitutively active PXR in rat carotid arteries potently attenuated proinflammatory responses. In addition, cDNA microarray revealed a large number of the PXR-activated endothelial genes whose products are responsible for major steps of detoxification, including phase I and II metabolizing enzymes and transporters. These detoxification genes in ECs are induced by LSS in ECs in a PXR-dependent manner. In conclusion, our results indicate that PXR represents a flow-activated detoxification system to protect ECs against damage by xeno- and endobiotics.

  7. Shear stress activation of nuclear receptor PXR in endothelial detoxification

    PubMed Central

    Wang, Xiaohong; Fang, Xi; Zhou, Jing; Chen, Zhen; Zhao, Beilei; Xiao, Lei; Liu, Ao; Li, Yi-Shuan J.; Shyy, John Y.-J.; Guan, Youfei; Chien, Shu; Wang, Nanping

    2013-01-01

    Endothelial cells (ECs) are constantly exposed to xenobiotics and endobiotics or their metabolites, which perturb EC function, as well as to shear stress, which plays a crucial role in vascular homeostasis. Pregnane X receptor (PXR) is a nuclear receptor and a key regulator of the detoxification of xeno- and endobiotics. Here we show that laminar shear stress (LSS), the atheroprotective flow, activates PXR in ECs, whereas oscillatory shear stress, the atheroprone flow, suppresses PXR. LSS activation of PXR in cultured ECs led to the increased expression of a PXR target gene, multidrug resistance 1 (MDR1). An in vivo study using rats showed that the expression of MDR1 was significantly higher in the endothelium from the descending thoracic aorta, where flow is mostly laminar, than from the inner curvature of aortic arch, where flow is disturbed. Functionally, LSS-activated PXR protects ECs from apoptosis triggered by doxorubicin via the induction of MDR1 and other detoxification genes. PXR also suppressed the expression of proinflammatory adhesion molecules and monocyte adhesion in response to TNF-α and lipopolysaccharide. Overexpression of a constitutively active PXR in rat carotid arteries potently attenuated proinflammatory responses. In addition, cDNA microarray revealed a large number of the PXR-activated endothelial genes whose products are responsible for major steps of detoxification, including phase I and II metabolizing enzymes and transporters. These detoxification genes in ECs are induced by LSS in ECs in a PXR-dependent manner. In conclusion, our results indicate that PXR represents a flow-activated detoxification system to protect ECs against damage by xeno- and endobiotics. PMID:23878263

  8. Endothelial fluid shear stress sensing in vascular health and disease

    PubMed Central

    Baeyens, Nicolas; Bandyopadhyay, Chirosree; Coon, Brian G.; Yun, Sanguk; Schwartz, Martin A.

    2016-01-01

    Endothelial cells transduce the frictional force from blood flow (fluid shear stress) into biochemical signals that regulate gene expression and cell behavior via specialized mechanisms and pathways. These pathways shape the vascular system during development and during postnatal and adult life to optimize flow to tissues. The same pathways also contribute to atherosclerosis and vascular malformations. This Review covers recent advances in basic mechanisms of flow signaling and the involvement of these mechanisms in vascular physiology, remodeling, and these diseases. We propose that flow sensing pathways that govern normal morphogenesis can contribute to disease under pathological conditions or can be altered to induce disease. Viewing atherosclerosis and vascular malformations as instances of pathological morphogenesis provides a unifying perspective that may aid in developing new therapies. PMID:26928035

  9. Impact of bifurcation dual stenting on endothelial shear stress

    PubMed Central

    Chen, Henry Y.; Koo, Bon-Kwon

    2015-01-01

    Despite advances in percutaneous coronary interventions and the introduction of drug eluding stents, in-stent restenosis and stent thrombosis remain a clinically significant problem for bifurcations. The aim of this study is to determine the effect of dual bifurcation stenting on hemodynamic parameters known to influence restenosis and thrombosis. We hypothesized that double stenting, especially with a longer side branch (SB) stent, likely has a negative effect on wall shear stress (WSS), WSS gradient (WSSG), and oscillatory shear index (OSI). To test this hypothesis, we developed computational models of dual stents at bifurcations and non-Newtonian blood simulations. The models were then interfaced, meshed, and solved in a validated finite-element package. Longer and shorter stents at the SB and provisional stenting were compared. It was found that stents placed in the SB at a bifurcation lowered WSS, but elevated WSSG and OSI. Dual stenting with longer SB stent had the most adverse impact on SB endothelial WSS, WSSG, and OSI, with low WSS region up to 50% more than the case with shorter SB stent. The simulations also demonstrated flow disturbances resulting from SB stent struts protruding into the main flow field near the carina, which may have implications on stent thrombosis. The simulations predict a negative hemodynamic role for SB stenting, which is exaggerated with a longer stent, consistent with clinical trial findings that dual-stenting is comparable or inferior to provisional stenting. PMID:26183473

  10. Localized α4 Integrin Phosphorylation Directs Shear Stress-Induced Endothelial Cell Alignment

    PubMed Central

    Goldfinger, Lawrence E.; Tzima, Eleni; Stockton, Rebecca; Kiosses, William B.; Kinbara, Kayoko; Tkachenko, Eugene; Gutierrez, Edgar; Groisman, Alex; Nguyen, Phu; Chien, Shu; Ginsberg1, Mark H.

    2009-01-01

    Vascular endothelial cells respond to laminar shear stress by aligning in the direction of flow, a process which may contribute to athero-protection. Here we report that localized α4 integrin phosphorylation is a mechanism for establishing the directionality of shear stress-induced alignment in microvascular endothelial cells. Within 5 minutes of exposure to a physiological level of shear stress, endothelial α4 integrins became phosphorylated on Ser988. In wounded monolayers, phosphorylation was enhanced at the downstream edges of cells relative to the source of flow. The shear-induced α4 integrin phosphorylation was blocked by inhibitors of cAMP-dependent protein kinase A (PKA), an enzyme involved in the alignment of endothelial cells under prolonged shear. Moreover, shear-induced localized activation of the small GTPase Rac1, which specifies the directionality of endothelial alignment, was similarly blocked by PKA inhibitors. Furthermore, endothelial cells bearing a non-phosphorylatable α4(S988A) mutation failed to align in response to shear stress, thus establishing α4 as a relevant PKA substrate. We thereby show that shear-induced PKA-dependent α4 integrin phosphorylation at the downstream edge of endothelial cells promotes localized Rac1 activation, which in turn directs cytoskeletal alignment in response to shear stress. PMID:18583710

  11. Shear stress reduces protease activated receptor-1 expression in human endothelial cells

    NASA Technical Reports Server (NTRS)

    Nguyen, K. T.; Eskin, S. G.; Patterson, C.; Runge, M. S.; McIntire, L. V.

    2001-01-01

    Shear stress has been shown to regulate several genes involved in the thrombotic and proliferative functions of endothelial cells. Thrombin receptor (protease-activated receptor-1: PAR-1) increases at sites of vascular injury, which suggests an important role for PAR-1 in vascular diseases. However, the effect of shear stress on PAR-1 expression has not been previously studied. This work investigates effects of shear stress on PAR-1 gene expression in both human umbilical vein endothelial cells (HUVECs) and microvascular endothelial cells (HMECs). Cells were exposed to different shear stresses using a parallel plate flow system. Northern blot and flow cytometry analysis showed that shear stress down-regulated PAR-1 messenger RNA (mRNA) and protein levels in both HUVECs and HMECs but with different thresholds. Furthermore, shear-reduced PAR-1 mRNA was due to a decrease of transcription rate, not increased mRNA degradation. Postshear stress release of endothelin-1 in response to thrombin was reduced in HUVECs and HMECs. Moreover, inhibitors of potential signaling pathways applied during shear stress indicated mediation of the shear-decreased PAR-1 expression by protein kinases. In conclusion, shear stress exposure reduces PAR-1 gene expression in HMECs and HUVECs through a mechanism dependent in part on protein kinases, leading to altered endothelial cell functional responses to thrombin.

  12. Role of glypican-1 in endothelial NOS activation under various steady shear stress magnitudes.

    PubMed

    Zeng, Ye; Liu, Jingxia

    2016-11-01

    Blood flow patterns in proatherogenic and antiatherogenic regions are rather different. We hypothesize that the laminar flow with steady shear stress increased nitric oxide (NO) bioavailability while disturbed flow with low shear stress reduced it, which is mediating by glypican-1. Thus, we detected the expression of glypican-1 under different shear stress magnitudes, and tested whether the magnitude of shear stress determines the level of endothelial NO synthase (eNOS) via glypican-1 by using phosphatidylinositol phospholipase C (PI-PLC). Results revealed that the expression of glypican-1 depends on the magnitude and duration of shear stress loading. Activation of eNOS in HUVECs is downregulated by 4dyn/cm(2) of shear stress, but is upregulated by 15dyn/cm(2). Removal of glypican-1 significantly suppressed the 15dyn/cm(2) shear stress-induced eNOS activity, and further reduced the 4dyn/cm(2)-inhibited eNOS activity. Therefore, eNOS activation depends on shear stress magnitudes and is mediated by glypican-1. The role of glypican-1 in mediating the eNOS activation under shear stress might involve in protecting the endothelial function against disturbed flow and enhancing the sensitive of the endothelial cell to laminar flow, supporting a potential role of glypican-1 against atherosclerosis.

  13. Shear stress-induced mitochondrial biogenesis decreases the release of microparticles from endothelial cells

    PubMed Central

    Kim, Ji-Seok; Kim, Boa; Lee, Hojun; Thakkar, Sunny; Babbitt, Dianne M.; Eguchi, Satoru; Brown, Michael D.

    2015-01-01

    The concept of enhancing structural integrity of mitochondria has emerged as a novel therapeutic option for cardiovascular disease. Flow-induced increase in laminar shear stress is a potent physiological stimulant associated with exercise, which exerts atheroprotective effects in the vasculature. However, the effect of laminar shear stress on mitochondrial remodeling within the vascular endothelium and its related functional consequences remain largely unknown. Using in vitro and in vivo complementary studies, here, we report that aerobic exercise alleviates the release of endothelial microparticles in prehypertensive individuals and that these salutary effects are, in part, mediated by shear stress-induced mitochondrial biogenesis. Circulating levels of total (CD31+/CD42a−) and activated (CD62E+) microparticles released by endothelial cells were significantly decreased (∼40% for both) after a 6-mo supervised aerobic exercise training program in individuals with prehypertension. In cultured human endothelial cells, laminar shear stress reduced the release of endothelial microparticles, which was accompanied by an increase in mitochondrial biogenesis through a sirtuin 1 (SIRT1)-dependent mechanism. Resveratrol, a SIRT1 activator, treatment showed similar effects. SIRT1 knockdown using small-interfering RNA completely abolished the protective effect of shear stress. Disruption of mitochondrial integrity by either antimycin A or peroxisome proliferator-activated receptor-γ coactivator-1α small-interfering RNA significantly increased the number of total, and activated, released endothelial microparticles, and shear stress restored these back to basal levels. Collectively, these data demonstrate a critical role of endothelial mitochondrial integrity in preserving endothelial homeostasis. Moreover, prolonged laminar shear stress, which is systemically elevated during aerobic exercise in the vessel wall, mitigates endothelial dysfunction by promoting mitochondrial

  14. Human brain microvascular endothelial cells resist elongation due to shear stress.

    PubMed

    Reinitz, Adam; DeStefano, Jackson; Ye, Mao; Wong, Andrew D; Searson, Peter C

    2015-05-01

    Endothelial cells in straight sections of vessels are known to elongate and align in the direction of flow. This phenotype has been replicated in confluent monolayers of bovine aortic endothelial cells and human umbilical vein endothelial cells (HUVECs) in cell culture under physiological shear stress. Here we report on the morphological response of human brain microvascular endothelial cells (HBMECs) in confluent monolayers in response to shear stress. Using a microfluidic platform we image confluent monolayers of HBMECs and HUVECs under shear stresses up to 16 dyne cm(-2). From live-cell imaging we quantitatively analyze the cell morphology and cell speed as a function of time. We show that HBMECs do not undergo a classical transition from cobblestone to spindle-like morphology in response to shear stress. We further show that under shear stress, actin fibers are randomly oriented in the cells indicating that there is no cytoskeletal remodeling. These results suggest that HBMECs are programmed to resist elongation and alignment under shear stress, a phenotype that may be associated with the unique properties of the blood-brain barrier.

  15. Online quantitative phase imaging of vascular endothelial cells under fluid shear stress utilizing digital holographic microscopy

    NASA Astrophysics Data System (ADS)

    Odenthal-Schnittler, Maria; Schnittler, Hans Joachim; Kemper, Björn

    2016-03-01

    We have explored the utilization of quantitative phase imaging with digital holographic microscopy (DHM) as a novel tool for quantifying the dynamics of morphologic parameters (morphodynamics) of confluent endothelial cell layers under fluid shear stress conditions. Human umbilical vein endothelial cells (HUVECs) were exposed to fluid shear stress in a transparent cone/plate flow device (BioTech-Flow-System) and imaged with a modular setup for quantitative DHM phase imaging for up to 48 h. The resulting series of quantitative phase image sequences were analyzed for the average surface roughness of the cell layers and cell alignment. Our results demonstrate that quantitative phase imaging is a powerful and reliable tool to quantify the dynamics of morphological adaptation of endothelial cells to fluid shear stress.

  16. Endothelial dysfunction and monocyte recruitment in cells exposed to non-uniform shear stress.

    PubMed

    Cicha, Iwona; Goppelt-Struebe, Margarete; Yilmaz, Atilla; Daniel, Werner G; Garlichs, Christoph D

    2008-01-01

    Atherosclerosis results from a combination of local blood flow patterns and systemic risk factors. We investigated whether non-uniform shear stress at bifurcations induces pro-atherogenic endothelial dysfunction and monocyte recruitment. Bifurcating flow-through cell culture slides were used to expose HUVECs to laminar or non-uniform shear stress for 18 h at 10 dyne/cm(2). For the adhesion assay, HUVECs were subsequently perfused with medium containing THP-1 monocytes for 1 h. Protein expression was determined by immunofluorescence. In areas exposed to laminar shear stress, alignment of endothelial cells with the flow was observed, accompanied by upregulation of eNOS and downregulation of connective tissue growth factor (CTGF). In contrast, cells exposed to non-uniform shear stress near the outer walls of bifurcations were characterized by irregular, unaligned shape, induction of endothelin-1 and CTGF, as well as reduced eNOS expression. These atherogenic effects of non-uniform shear stress were prevented when cells were treated with statins (1 mumol/l) during flow. Under non-uniform shear stress, a slight induction of VCAM-1, ICAM-1, and E-/P-selectin was observed. In agreement with this, monocyte recruitment, which was nearly undetectable under laminar shear stress, was moderately induced by non-uniform shear stress (P<0.02). In conclusion, inhibition of antioxidative eNOS and upregulation of atherogenic proteins is the first step in non-uniform shear stress-mediated endothelial dysfunction, which in vivo in the presence of atherogenic risk factors may further enhance monocyte recruitment into the artery wall.

  17. Effect of shear stress on water and LDL transport through cultured endothelial cell monolayers.

    PubMed

    Kang, Hongyan; Cancel, Limary M; Tarbell, John M

    2014-04-01

    Previous animal experiments have shown that the transport of LDL into arterial walls is shear stress dependent. However, little work has probed shear effects on LDL transport in vitro where conditions are well defined and mechanisms are more easily explored. Therefore, we measured shear induced water and LDL fluxes across cultured bovine aortic endothelial (BAEC) monolayers in vitro and developed a three-pore model to describe the transport dynamics. Cell apoptosis was quantified by TdT-mediated dUTP nick end labeling (TUNEL) assay. We also examined the role of nitric oxide (NO) in shear induced water and LDL fluxes by incubating BAEC monolayers with an NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA). Our results show that direct exposure of endothelial monolayers to 12 dyn/cm2 shear stress for 3 h elicited a 2.37-fold increase in water flux (Jv), a 3.00-fold increase in LDL permeability (Pe), a 1.32-fold increase in LDL uptake, and a 1.68-fold increase in apoptotic rate. L-NMMA treatment of BAEC monolayers blocked shear induced Jv response, but had no significant effect on shear responses of Pe and cell apoptosis. A long time shear exposure (12 h) of endothelial monolayers reduced Pe and apoptotic rate close to the baseline. These results suggest that an acute change in shear stress from a static baseline state induces increases in water flux that are mediated by an NO dependent mechanism. On the other hand, the permeability of endothelial monolayers to LDL is enhanced by a short term-shear application and reduced nearly to the baseline level by a longer time shear exposure, positively correlated to the leaky junctions forming around apoptotic cells.

  18. Impact of peptide micropatterning on endothelial cell actin remodeling for cell alignment under shear stress.

    PubMed

    Chollet, Céline; Bareille, Reine; Rémy, Murielle; Guignandon, Alain; Bordenave, Laurence; Laroche, Gaetan; Durrieu, Marie-Christine

    2012-12-01

    HSVEC behavior under physiological shear stress in vitro is investigated on PET surfaces micropatterned with both RGDS and WQPPRARI peptides. This technique allows (i) creating geometries on surface to guide cell orientation under shear stress and (ii) controlling surface chemical composition in order to modulate cell behavior. Under shear stress, endothelial cells adhere on patterned PET surfaces and present a more rapid orientation in flow direction in comparison to cells cultured on homogeneous surfaces. Micropatterned surfaces presenting a large surface area ratio of RGDS/WQPPRARI peptides induce fibrillar adhesion, while surfaces presenting an equal RGDS/WQPPRARI peptides surface area ratio preferentially induce focal adhesion.

  19. Cooperative effects of matrix stiffness and fluid shear stress on endothelial cell behavior.

    PubMed

    Kohn, Julie C; Zhou, Dennis W; Bordeleau, François; Zhou, Allen L; Mason, Brooke N; Mitchell, Michael J; King, Michael R; Reinhart-King, Cynthia A

    2015-02-03

    Arterial hemodynamic shear stress and blood vessel stiffening both significantly influence the arterial endothelial cell (EC) phenotype and atherosclerosis progression, and both have been shown to signal through cell-matrix adhesions. However, the cooperative effects of fluid shear stress and matrix stiffness on ECs remain unknown. To investigate these cooperative effects, we cultured bovine aortic ECs on hydrogels matching the elasticity of the intima of compliant, young, or stiff, aging arteries. The cells were then exposed to laminar fluid shear stress of 12 dyn/cm(2). Cells grown on more compliant matrices displayed increased elongation and tighter EC-cell junctions. Notably, cells cultured on more compliant substrates also showed decreased RhoA activation under laminar shear stress. Additionally, endothelial nitric oxide synthase and extracellular signal-regulated kinase phosphorylation in response to fluid shear stress occurred more rapidly in ECs cultured on more compliant substrates, and nitric oxide production was enhanced. Together, our results demonstrate that a signaling cross talk between stiffness and fluid shear stress exists within the vascular microenvironment, and, importantly, matrices mimicking young and healthy blood vessels can promote and augment the atheroprotective signals induced by fluid shear stress. These data suggest that targeting intimal stiffening and/or the EC response to intima stiffening clinically may improve vascular health.

  20. Adaptive response of vascular endothelial cells to an acute increase in shear stress frequency.

    PubMed

    Zhang, Ji; Friedman, Morton H

    2013-09-15

    Local shear stress sensed by arterial endothelial cells is occasionally altered by changes in global hemodynamic parameters, e.g., heart rate and blood flow rate, as a result of normal physiological events, such as exercise. In a recently study (41), we demonstrated that during the adaptive response to increased shear magnitude, porcine endothelial cells exhibited an unique phenotype featuring a transient increase in permeability and the upregulation of a set of anti-inflammatory and antioxidative genes. In the present study, we characterize the adaptive response of these cells to an increase in shear frequency, another important hemodynamic parameter with implications in atherogenesis. Endothelial cells were preconditioned by a basal-level sinusoidal shear stress of 15 ± 15 dyn/cm(2) at 1 Hz, and the frequency was then elevated to 2 Hz. Endothelial permeability increased slowly after the frequency step-up, but the increase was relatively small. Using microarrays, we identified 37 genes that are sensitive to the frequency step-up. The acute increase in shear frequency upregulates a set of cell-cycle regulation and angiogenesis-related genes. The overall adaptive response to the increased frequency is distinctly different from that to a magnitude step-up. However, consistent with the previous study, our data support the notion that endothelial function during an adaptive response is different than that of fully adapted endothelial cells. Our studies may also provide insights into the beneficial effects of exercise on vascular health: transient increases in frequency may facilitate endothelial repair, whereas similar increases in shear magnitude may keep excessive inflammation and oxidative stress at bay.

  1. Evidence that release of adenosine triphosphate from endothelial cells during increased shear stress is vesicular.

    PubMed

    Bodin, P; Burnstock, G

    2001-12-01

    In response to increased shear stress, vascular endothelial cells release adenosine triphosphate (ATP) by an unknown mechanism. We have investigated this mechanism using different approaches. First, we discovered that quinacrine, used to locate intracellular stores of ATP bound to peptides, displayed a granular fluorescence, typical of vesicular storage. Second, we found that two inhibitors of vesicular transport (monensin and N-ethylmaleimide) produced a highly significant reduction in the release of ATP from vascular endothelial cells in response to increased shear stress. Preliminary experiments using inhibitors of the cystic fibrosis transmembrane regulator, the sulfonylurea receptor, and the multidrug resistance protein showed no involvement of these ATP-binding cassette transporter proteins (previously characterized in endothelial cells) in the mechanism of release of ATP. We suggest, therefore, that the release of ATP from vascular endothelial cells, like that of nerve cells, is probably by vesicular exocytosis.

  2. Pulsatile atheroprone shear stress affects the expression of transient receptor potential channels in human endothelial cells.

    PubMed

    Thilo, Florian; Vorderwülbecke, Bernd J; Marki, Alex; Krueger, Katharina; Liu, Ying; Baumunk, Daniel; Zakrzewicz, Andreas; Tepel, Martin

    2012-06-01

    The goal of the study was to assess whether pulsatile atheroprone shear stress modulates the expression of transient receptor potential (TRP) channels, TRPC3, TRPC6, TRPM7, and TRPV1 mRNA, in human umbilical vascular endothelial cells. Exposure of cultured vascular endothelial cells to defined shear stress, producing a constant laminar flow (generating a shear stress of 6 dyne/cm(2)), laminar pulsatile atheroprotective flow (with a mean shear stress of 20 dyne/cm(2)), or laminar atheroprone bidirectional flow (with a mean shear stress of 0 dyne/cm(2)) differentially induced TRPC6 and TRPV1 mRNA as measured by quantitative real-time RT-PCR and normalized to GAPDH expression. Thereby, TRPC6 and TRPV1 mRNA expressions were significantly increased after 24 hours of exposure to an atheroprone flow profile compared with an atheroprotective flow profile. Furthermore, the expression of transcription factors GATA1 and GATA4 was significantly correlated with the expression of TRPC6 mRNA. In contrast, after 24 hours of constant laminar flow, the expression of TRPC6 and TRPV1 mRNA was unchanged, whereas the expression of TRPC3 and TRPM7 was significantly higher in endothelial cells exposed to shear stress in comparison with endothelial cells grown under static conditions. There was a significant association between the expression of TRPC6 and tumor necrosis factor-α mRNA in human vascular tissue. No-flow and atheroprone flow conditions are equally characterized by an increase in the expression of tumor necrosis factor-α; however, inflammation-associated endothelial cell reactions may be further aggravated at atheroprone flow conditions by the increase of TRPV1 and TRPC6, as observed in our study.

  3. Suppression of endothelial t-PA expression by prolonged high laminar shear stress

    SciTech Connect

    Ulfhammer, Erik; Carlstroem, Maria; Bergh, Niklas; Larsson, Pia; Karlsson, Lena; Jern, Sverker

    2009-02-06

    Primary hypertension is associated with an impaired capacity for acute release of endothelial tissue-type plasminogen activator (t-PA), which is an important local protective response to prevent thrombus extension. As hypertensive vascular remodeling potentially results in increased vascular wall shear stress, we investigated the impact of shear on regulation of t-PA. Cultured human endothelial cells were exposed to low ({<=}1.5 dyn/cm{sup 2}) or high (25 dyn/cm{sup 2}) laminar shear stress for up to 48 h in two different experimental models. Using real-time RT-PCR and ELISA, shear stress was observed to time and magnitude-dependently suppress t-PA transcript and protein secretion to approximately 30% of basal levels. Mechanistic experiments revealed reduced nuclear protein binding to the t-PA specific CRE element (EMSA) and an almost completely abrogated shear response with pharmacologic JNK inhibition. We conclude that prolonged high laminar shear stress suppresses endothelial t-PA expression and may therefore contribute to the enhanced risk of arterial thrombosis in hypertensive disease.

  4. Dynamic Shear Stress Regulation of Inflammatory and Thrombotic Pathways in Baboon Endothelial Outgrowth Cells

    PubMed Central

    Hinds, Monica T.; Nerem, Robert M.

    2013-01-01

    Endothelial outgrowth cells (EOCs) have garnered much attention as a potential autologous endothelial source for vascular implants or in tissue engineering applications due to their ease of isolation and proliferative ability; however, how these cells respond to different hemodynamic cues is ill-defined. This study investigates the inflammatory and thrombotic response of baboon EOCs (BaEOCs) to four hemodynamic conditions using the cone and plate shear apparatus: steady, laminar shear stress (SS); pulsatile, nonreversing laminar shear stress (PS); oscillatory, laminar shear stress (OS); and net positive, pulsatile, reversing laminar shear stress (RS). In summary, endothelial nitric oxide synthase (eNOS) mRNA was significantly upregulated by SS compared to OS. No differences were found in the mRNA levels of the inflammatory markers intercellular adhesion molecule-1 (ICAM-1), E-selectin, and vascular cell adhesion molecule-1 (VCAM-1) between the shear conditions; however, OS significantly increased the number of monocytes bound when compared to SS. Next, SS increased the anti-thrombogenic mRNA levels of CD39, thrombomodulin, and endothelial protein-C receptor (EPCR) compared to OS. SS also significantly increased CD39 and EPCR mRNA levels compared to RS. Finally, no significant differences were detected when comparing pro-thrombotic tissue factor mRNA or its activity levels. These results indicate that shear stress can have beneficial (SS) or adverse (OS, RS) effects on the inflammatory or thrombotic potential of EOCs. Further, these results suggest SS hemodynamic preconditioning may be optimal in increasing the efficacy of a vascular implant or in tissue-engineered applications that have incorporated EOCs. PMID:23406430

  5. Effect of shear stress on asymmetric dimethylarginine release from vascular endothelial cells.

    PubMed

    Osanai, Tomohiro; Saitoh, Masayuki; Sasaki, Satoko; Tomita, Hirofumi; Matsunaga, Toshiro; Okumura, Ken

    2003-11-01

    We demonstrated recently that plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, are increased by high salt intake concomitantly with a decrease in plasma levels of NO in human hypertension. We investigated the effect of shear stress on ADMA release in 2 types of cells: transformed human umbilical vein endothelial cells (HUVECs; cell line ECV-304) and HUVECs. Exposure of ECV-304 cells and HUVECs to shear stress with the use of a cone-plate viscometer enhanced gene expression of protein arginine methyltransferase (PRMT-1), ADMA synthase. In HUVECs, the ratio of PRMT-1 to glyceraldehyde 3-phosphate dehydrogenase mRNA was increased by 2-fold by a shear stress of > or =15 dyne/cm2. A dominant-negative mutant of IkappaB kinase alpha and troglitazone at 8 micromol/L, an activator of peroxisome proliferator-activated receptor gamma, abolished the shear stress-induced increase in PRMT-1 gene expression in parallel with the blockade of nuclear factor (NF)-kappaB translocation into the nucleus. The activity of dimethylarginine dimethylaminohydrolase, the degradation enzyme of ADMA, was unchanged after shear stress < or =15 dyne/cm2 and was enhanced by 1.48+/-0.06-fold (P<0.05) by shear stress at 25 dyne/cm2. The release of ADMA was increased by 1.64+/-0.10-fold (P<0.05) by shear stress at 15 dyne/cm2 but was not affected by shear stress at 25 dyne/cm2. These results indicate that shear stress enhances gene expression of PRMT-1 and ADMA release via activation of the NF-kappaB pathway. Shear stress at higher magnitudes facilitates the degradation of ADMA, thus returning ADMA release levels to baseline.

  6. Shear stress-induced redistribution of the glycocalyx on endothelial cells in vitro.

    PubMed

    Bai, Ke; Wang, Wen

    2014-04-01

    The glycocalyx is the inner most layer of the endothelium that is in direct contact with the circulating blood. Shear stress affects its synthesis and reorganization. This study focuses on changes in the spatial distribution of the glycocalyx caused by shear stimulation and its recovery following the removal of the shear stress. Sialic acid components of the glycocalyx on human umbilical vain endothelial cells are observed using confocal microscopy. The percentage area of the cell membrane covered by the glycocalyx, as well as the average fluorescence intensity ratio between the apical and edge areas of the cell is used to assess the spatial distribution of the glycocalyx on the cell membrane. Our results show that following 24 h shear stimulation, the glycocalyx relocates near the edge of endothelial cells (i.e., cell-cell junction regions). Following the removal of the shear stress, the glycocalyx redistributes and gradually appears in the apical region of the cell membrane. This redistribution is faster in the early hours (<4 h) after shear stimulation than that in the later stage (e.g., between 8 and 24 h). We further investigate the recovery of the glycocalyx after its enzyme degradation under either static or shear flow conditions. Our results show that following 24 h recovery under shear flow, the glycocalyx reappears predominantly near the edge of endothelial cells. Static and shear flow conditions result in notable changes in the spatial recovery of the glycocalyx, but the difference is not statistically significant. We hypothesize that newly synthesized glycocalyx is not structurally well developed. Its weak interaction with flow results in less than significant redistribution, contrary to what has been observed for a well-developed glycocalyx layer.

  7. Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells.

    PubMed

    Fleming, Ingrid; Fisslthaler, Beate; Dixit, Madhulika; Busse, Rudi

    2005-09-15

    The application of fluid shear stress to endothelial cells elicits the formation of nitric oxide (NO) and phosphorylation of the endothelial NO synthase (eNOS). Shear stress also elicits the enhanced tyrosine phosphorylation of endothelial proteins, especially of those situated in the vicinity of cell-cell contacts. Since a major constituent of these endothelial cell-cell contacts is the platelet endothelial cell adhesion molecule-1 (PECAM-1) we assessed the role of PECAM-1 in the activation of eNOS. In human endothelial cells, shear stress induced the tyrosine phosphorylation of PECAM-1 and enhanced the association of PECAM-1 with eNOS. Endothelial cell stimulation with shear stress elicited the phosphorylation of Akt and eNOS as well as of the AMP-activated protein kinase (AMPK). While the shear-stress-induced tyrosine phosphorylation of PECAM-1 as well as the serine phosphorylation of Akt and eNOS were abolished by the pre-treatment of cells with the tyrosine kinase inhibitor PP1 the phosphorylation of AMPK was unaffected. Down-regulation of PECAM-1 using a siRNA approach attenuated the shear-stress-induced phosphorylation of Akt and eNOS, as well as the shear-stress-induced accumulation of cyclic GMP levels while the shear-stress-induced phosphorylation of AMPK remained intact. A comparable attenuation of Akt and eNOS (but not AMPK) phosphorylation and NO production was also observed in endothelial cells generated from PECAM-1-deficient mice. These data indicate that the shear-stress-induced activation of Akt and eNOS in endothelial cells is modulated by the tyrosine phosphorylation of PECAM-1 whereas the shear-stress-induced phosphorylation of AMPK is controlled by an alternative signaling pathway.

  8. Shear stress-induced Ets-1 modulates protease inhibitor expression in microvascular endothelial cells.

    PubMed

    Milkiewicz, Malgorzata; Uchida, Cassandra; Gee, Eric; Fudalewski, Tomasz; Haas, Tara L

    2008-11-01

    Elevated shear stress within the skeletal muscle microvasculature is implicated in the induction of a longitudinal splitting form of angiogenesis, which is characterized by the lack of basement membrane breakage. We investigated whether the transcriptional regulator, Ets-1, is responsive to changes in hemodynamic forces and if so, whether Ets-1 controls microvascular endothelial cell integrity by inducing the expression of inhibitors of matrix degrading proteases. Rats were treated with prazosin for 2, 4, and 7 days to increase in microvascular shear stress in hindlimb skeletal muscles. In complimentary in vitro experiments, rat microvascular skeletal muscle endothelial cells were exposed to laminar shear stress (15 dyne/cm(2)) for 0.5, 2, and 24 h. TaqMan PCR analysis of laser microdissected capillaries isolated from EDL muscles demonstrated transient (after 2 days) induction of Ets-1 gene expression. In cultured cells, a transient up-regulation of Ets-1 mRNA was observed after 2 h shear stimulation, accompanied by increased phosphorylation of Ets-1 and enhanced Ets-1 DNA binding activity. This response was modulated by ERK1/2 and p38 MAP kinases, but was not dependent on NOS or COX-2 activity. PAI-1, TIMP-1 and TIMP-3 mRNA were elevated significantly in prazosin treated EDL, and in response to shear stimulation in vitro. In cultured endothelial cells, Ets-1 RNA interference abolished the shear-induced increases in Ets-1, PAI-1, TIMP-1, and TIMP-3 mRNA expression. These results suggest that enhanced laminar shear stress may act to preserve the integrity of microvascular walls in part through Ets-1-dependent induction of protease inhibitors.

  9. Vascular endothelial cell membranes differentiate between stretch and shear stress through transitions in their lipid phases.

    PubMed

    Yamamoto, Kimiko; Ando, Joji

    2015-10-01

    Vascular endothelial cells (ECs) respond to the hemodynamic forces stretch and shear stress by altering their morphology, functions, and gene expression. However, how they sense and differentiate between these two forces has remained unknown. Here we report that the plasma membrane itself differentiates between stretch and shear stress by undergoing transitions in its lipid phases. Uniaxial stretching and hypotonic swelling increased the lipid order of human pulmonary artery EC plasma membranes, thereby causing a transition from the liquid-disordered phase to the liquid-ordered phase in some areas, along with a decrease in membrane fluidity. In contrast, shear stress decreased the membrane lipid order and increased membrane fluidity. A similar increase in lipid order occurred when the artificial lipid bilayer membranes of giant unilamellar vesicles were stretched by hypotonic swelling, indicating that this is a physical phenomenon. The cholesterol content of EC plasma membranes significantly increased in response to stretch but clearly decreased in response to shear stress. Blocking these changes in the membrane lipid order by depleting membrane cholesterol with methyl-β-cyclodextrin or by adding cholesterol resulted in a marked inhibition of the EC response specific to stretch and shear stress, i.e., phosphorylation of PDGF receptors and phosphorylation of VEGF receptors, respectively. These findings indicate that EC plasma membranes differently respond to stretch and shear stress by changing their lipid order, fluidity, and cholesterol content in opposite directions and that these changes in membrane physical properties are involved in the mechanotransduction that activates membrane receptors specific to each force.

  10. Effects of different types of fluid shear stress on endothelial cell proliferation and survival.

    PubMed

    Kadohama, Takayuki; Nishimura, Kengo; Hoshino, Yuji; Sasajima, Tadahiro; Sumpio, Bauer E

    2007-07-01

    We attempted to clarify the effect of different types of shear stress on endothelial cell (EC) proliferation and survival. Bovine aortic ECs were subjected to either steady laminar, 1 Hz pulsatile, or 1 Hz to and fro shear at 14 dyne/cm(2). % of BrdU positive EC was 14.3 +/- 1.6% in steady, 21.5 +/- 3.2% in pulsatile, and 11.4 +/- 2.4% in to and fro after 4 h, respectively (P < 0.05). Pulsatile shear compared with static control. Rapamycin reduced BrdU incorporation in all shear regimens (P < 0.001). However, it was still higher in EC exposed to pulsatile shear than the other regimens (P < 0.005). PD98059 completely abolished the increased BrdU incorporation in all shear regimens, including pulsatile shear. Pulsatile shear had significantly elevated ERK1/2 phosphorylation at 5 min compared with steady (P < 0.05) and to and fro shear (P < 0.01) while there was no significant difference in pp70(S6k) phosphorylation between any shear regimen. The ratio of apoptotic cells in serum deprived EC in the presence of steady laminar, pulsatile and to and fro shear for 4 h were 2.7 +/- 0.78%, 2.7 +/- 0.42%, and 2.9 +/- 0.62%, respectively while after the addition of serum for 4 h, it was 4.3 +/- 0.73%. All shear regimens phosphorylated AKT in a time-dependent manner with no significant difference between regimens. Our results demonstrate that different types of shear stress regimens have different effects on EC and may account for the variable response of EC to hemodynamics in the circulation.

  11. [The anticonstrictor effect of endothelial sensitivity to shear stress].

    PubMed

    Mel'kumiants, A M; Balashov, S A; Kartamyshev, S P

    1996-04-01

    Responses of the femoral artery to drops in transmural pressure and to norepinephrine revealed the anticonstrictor effect of the endothelium sensitivity upon a stress action. The effect was less obvious at high flow rate. The data obtained suggests that the endothelium sensitivity to stress inhibits the arterial constrictor responses irrespective of the nature of the constrictor stimuli.

  12. Endothelial dysfunction following prolonged sitting is mediated by a reduction in shear stress.

    PubMed

    Restaino, Robert M; Walsh, Lauren K; Morishima, Takuma; Vranish, Jennifer R; Martinez-Lemus, Luis A; Fadel, Paul J; Padilla, Jaume

    2016-03-01

    We and others have recently reported that prolonged sitting impairs endothelial function in the leg vasculature; however, the mechanism(s) remain unknown. Herein, we tested the hypothesis that a sustained reduction in flow-induced shear stress is the underlying mechanism by which sitting induces leg endothelial dysfunction. Specifically, we examined whether preventing the reduction in shear stress during sitting would abolish the detrimental effects of sitting on popliteal artery endothelial function. In 10 young healthy men, bilateral measurements of popliteal artery flow-mediated dilation were performed before and after a 3-h sitting period during which one foot was submerged in 42°C water (i.e., heated) to increase blood flow and thus shear stress, whereas the contralateral leg remained dry and served as internal control (i.e., nonheated). During sitting, popliteal artery mean shear rate was reduced in the nonheated leg (pre-sit, 42.9 ± 4.5 s(-1); and 3-h sit, 23.6 ± 3.3 s(-1); P < 0.05) but not in the heated leg (pre-sit, 38.9 ± 3.4 s(-1); and 3-h sit, 63.9 ± 16.9 s(-1); P > 0.05). Popliteal artery flow-mediated dilation was impaired after 3 h of sitting in the nonheated leg (pre-sit, 7.1 ± 1.4% vs. post-sit, 2.8 ± 0.9%; P < 0.05) but not in the heated leg (pre-sit: 7.3 ± 1.5% vs. post-sit, 10.9 ± 1.8%; P > 0.05). Collectively, these data suggest that preventing the reduction of flow-induced shear stress during prolonged sitting with local heating abolishes the impairment in popliteal artery endothelial function. Thus these findings are consistent with the hypothesis that sitting-induced leg endothelial dysfunction is mediated by a reduction in shear stress.

  13. Endothelial dysfunction following prolonged sitting is mediated by a reduction in shear stress

    PubMed Central

    Restaino, Robert M.; Walsh, Lauren K.; Morishima, Takuma; Vranish, Jennifer R.; Martinez-Lemus, Luis A.; Fadel, Paul J.

    2016-01-01

    We and others have recently reported that prolonged sitting impairs endothelial function in the leg vasculature; however, the mechanism(s) remain unknown. Herein, we tested the hypothesis that a sustained reduction in flow-induced shear stress is the underlying mechanism by which sitting induces leg endothelial dysfunction. Specifically, we examined whether preventing the reduction in shear stress during sitting would abolish the detrimental effects of sitting on popliteal artery endothelial function. In 10 young healthy men, bilateral measurements of popliteal artery flow-mediated dilation were performed before and after a 3-h sitting period during which one foot was submerged in 42°C water (i.e., heated) to increase blood flow and thus shear stress, whereas the contralateral leg remained dry and served as internal control (i.e., nonheated). During sitting, popliteal artery mean shear rate was reduced in the nonheated leg (pre-sit, 42.9 ± 4.5 s−1; and 3-h sit, 23.6 ± 3.3 s−1; P < 0.05) but not in the heated leg (pre-sit, 38.9 ± 3.4 s−1; and 3-h sit, 63.9 ± 16.9 s−1; P > 0.05). Popliteal artery flow-mediated dilation was impaired after 3 h of sitting in the nonheated leg (pre-sit, 7.1 ± 1.4% vs. post-sit, 2.8 ± 0.9%; P < 0.05) but not in the heated leg (pre-sit: 7.3 ± 1.5% vs. post-sit, 10.9 ± 1.8%; P > 0.05). Collectively, these data suggest that preventing the reduction of flow-induced shear stress during prolonged sitting with local heating abolishes the impairment in popliteal artery endothelial function. Thus these findings are consistent with the hypothesis that sitting-induced leg endothelial dysfunction is mediated by a reduction in shear stress. PMID:26747508

  14. Polyethylene terephthalate membrane grafted with peptidomimetics: endothelial cell compatibility and retention under shear stress.

    PubMed

    Rémy, Murielle; Bareille, Reine; Rerat, Vincent; Bourget, Chantal; Marchand-Brynaert, Jacqueline; Bordenave, Laurence

    2013-01-01

    The present work aimed to treat a polyethylene terephthalate (PET) surface to make the biomaterial more 'attractive' in terms of attachment and shear stress response to endothelial cells with a view to possible applications in vascular grafting. A surface wet-chemistry protocol was applied to graft track-etched PET membranes with RGD peptidomimetics based on the tyrosine template and active at the nano-level vs. isolated human αvβ3 receptor, which was monitored by X-ray photoelectron spectroscopy, contact angle measurement and atomic force microscopy for characterization. A primary culture of human saphenous vein endothelial cells was used before and after sterilization of the membranes (heat treatment or γ-ray irradiation) to test the benefit of grafting. The optimal surface concentrations of grafted molecules were around 50 pmol/cm². Compared to GRGDS, the peptidomimetics promoted cell attachment with similar or slightly better performances. Endothelialized grafted supports were further exposed to 2 h of shear stress mimicking arterial conditions. Cells were lost on non-grafted PET whereas cells on grafted polymers sterilized by γ-ray irradiation withstood forces with no significant difference in focal contacts. At the mRNA level, cells on functionalized PET were able to respond to shear stress with NFkB upregulation. Thus, grafting of peptidomimetics as ligands of the αvβ3 integrin could be a relevant strategy to improve the adhesion of human endothelial cells and to obtain an efficient endothelialized PET for the surgery of small-diameter vascular prostheses.

  15. Nature's rheologists: Lymphatic endothelial cells control migration in response to shear stress

    NASA Astrophysics Data System (ADS)

    Fuller, Gerald; Dunn, Alex; Surya, Vinay

    2015-03-01

    Endothelial cells (ECs) line the inner surface of blood and lymphatic vessels and are sensitive to fluid flow as part of their physiological function. EC organization, migration and vessel development are profoundly influenced by shear stresses, with important implications in cardiovascular disease and tumor metastasis. How ECs sense fluid flow is a central and unanswered question in cardiovascular biology. We developed a high-throughput live-cell flow chamber that models the gradients in wall shear stress experienced by ECs in vivo. Live-cell imaging allows us to probe cellular responses to flow, most notably EC migration, which has a key role in vessel remodeling. We find that most EC subtypes, including ECs from the venous, arterial, and microvascular systems, migrate in the flow direction. In contrast, human lymphatic microvascular ECs (hLMVECs) migrate against flow and up spatial gradients in wall shear stress. Further experiments reveal that hLMVECs are sensitive to the magnitude, direction, and the local spatial gradients in wall shear stress. Lastly, recent efforts have aimed to link this directional migration to spatial gradients in cell-mediated small molecule emission that may be linked to the gradient in wall shear stress.

  16. Role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress.

    PubMed

    McNally, J Scott; Davis, Michael E; Giddens, Don P; Saha, Aniket; Hwang, Jinah; Dikalov, Sergey; Jo, Hanjoong; Harrison, David G

    2003-12-01

    Oscillatory shear stress occurs at sites of the circulation that are vulnerable to atherosclerosis. Because oxidative stress contributes to atherosclerosis, we sought to determine whether oscillatory shear stress increases endothelial production of reactive oxygen species and to define the enzymes responsible for this phenomenon. Bovine aortic endothelial cells were exposed to static, laminar (15 dyn/cm2), and oscillatory shear stress (+/-15 dyn/cm2). Oscillatory shear increased superoxide (O2.-) production by more than threefold over static and laminar conditions as detected using electron spin resonance (ESR). This increase in O2*- was inhibited by oxypurinol and culture of endothelial cells with tungsten but not by inhibitors of other enzymatic sources. Oxypurinol also prevented H2O2 production in response to oscillatory shear stress as measured by dichlorofluorescin diacetate and Amplex Red fluorescence. Xanthine-dependent O2*- production was increased in homogenates of endothelial cells exposed to oscillatory shear stress. This was associated with decreased xanthine dehydrogenase (XDH) protein levels and enzymatic activity resulting in an elevated ratio of xanthine oxidase (XO) to XDH. We also studied endothelial cells lacking the p47phox subunit of the NAD(P)H oxidase. These cells exhibited dramatically depressed O2*- production and had minimal XO protein and activity. Transfection of these cells with p47phox restored XO protein levels. Finally, in bovine aortic endothelial cells, prolonged inhibition of the NAD(P)H oxidase with apocynin decreased XO protein levels and prevented endothelial cell stimulation of O2*- production in response to oscillatory shear stress. These data suggest that the NAD(P)H oxidase maintains endothelial cell XO levels and that XO is responsible for increased reactive oxygen species production in response to oscillatory shear stress.

  17. Role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress

    NASA Technical Reports Server (NTRS)

    McNally, J. Scott; Davis, Michael E.; Giddens, Don P.; Saha, Aniket; Hwang, Jinah; Dikalov, Sergey; Jo, Hanjoong; Harrison, David G.

    2003-01-01

    Oscillatory shear stress occurs at sites of the circulation that are vulnerable to atherosclerosis. Because oxidative stress contributes to atherosclerosis, we sought to determine whether oscillatory shear stress increases endothelial production of reactive oxygen species and to define the enzymes responsible for this phenomenon. Bovine aortic endothelial cells were exposed to static, laminar (15 dyn/cm2), and oscillatory shear stress (+/-15 dyn/cm2). Oscillatory shear increased superoxide (O2.-) production by more than threefold over static and laminar conditions as detected using electron spin resonance (ESR). This increase in O2*- was inhibited by oxypurinol and culture of endothelial cells with tungsten but not by inhibitors of other enzymatic sources. Oxypurinol also prevented H2O2 production in response to oscillatory shear stress as measured by dichlorofluorescin diacetate and Amplex Red fluorescence. Xanthine-dependent O2*- production was increased in homogenates of endothelial cells exposed to oscillatory shear stress. This was associated with decreased xanthine dehydrogenase (XDH) protein levels and enzymatic activity resulting in an elevated ratio of xanthine oxidase (XO) to XDH. We also studied endothelial cells lacking the p47phox subunit of the NAD(P)H oxidase. These cells exhibited dramatically depressed O2*- production and had minimal XO protein and activity. Transfection of these cells with p47phox restored XO protein levels. Finally, in bovine aortic endothelial cells, prolonged inhibition of the NAD(P)H oxidase with apocynin decreased XO protein levels and prevented endothelial cell stimulation of O2*- production in response to oscillatory shear stress. These data suggest that the NAD(P)H oxidase maintains endothelial cell XO levels and that XO is responsible for increased reactive oxygen species production in response to oscillatory shear stress.

  18. Real-time quantification of endothelial response to shear stress and vascular modulators.

    PubMed

    DeStefano, Jackson G; Williams, Ashley; Wnorowski, Alexa; Yimam, Nahom; Searson, Peter C; Wong, Andrew D

    2017-03-27

    Quiescence is commonly used to describe the inactive state of endothelial cells (ECs) in monolayers that have reached homeostasis. Experimentally quiescence is usually described in terms of the relative change in cell activity (e.g. turnover, speed, etc.) in response to a perturbation (e.g. solute, shear stress, etc.). The objective of this study is to provide new insight into EC quiescence by quantitatively defining the morphology and activity of confluent cell monolayers in response to shear stress and vascular modulators. Confluent monolayers of human umbilical vein ECs (HUVECs) were subjected to a range of shear stresses (4-16 dyne cm(-2)) under steady flow. Using phase contrast, time-lapse microscopy and image analysis, we quantified EC morphology, speed, proliferation, and apoptosis rates over time and detected differences in monolayer responses under various media conditions: basal media supplemented with growth factors, interleukin-8, or cyclic AMP. In all conditions, we observed a transition from cobblestone to spindle-like morphology in a dose-dependent manner due to shear stress. Cyclic AMP enhanced the elongation and alignment of HUVECs due to shear stress and reduced steady state cell speed. We observed the lowest proliferation rates below 8 dyne cm(-2) and found that growth factors and cyclic AMP reduced proliferation and apoptosis; interleukin-8 similarly decreased proliferation, but increased apoptosis. We have quantified the response of ECs in confluent monolayers to shear stress and vascular modulators in terms of morphology, speed, proliferation and apoptosis and have established quantifiable metrics of cell activity to define vascular quiescence under shear stress.

  19. Spatially and temporally resolved quantification of endothelial cell modification in response to shear stress

    NASA Astrophysics Data System (ADS)

    Lambert, Lori; Pipinos, Iraklis; Baxter, Timothy; Leighton, Richard; Wei, Timothy

    2015-11-01

    This talk contains a resport on in vivo measurements made over a confluent layer of bovine endothelial cells in a microchannel. The ultimate goal of the experiments is to understand and model cellular response to fluid stresses and the ensuing transport across the endothelial layer. High resolution μ PTV measurements were made to quantify the cellular response to steady shear rates of 5, 10 and 20 dynes/cm2. Surface topography, shear and pressure distributions were calculated from sets of velocity fields made in planes parallel to the wall. For each experiment, measurements were made in three-hour intervals for eighteen hours. To validate the methodology, the pH of the medium was varied so that the health of the cells would vary. Clear differences in topography and cell orientation were found. Implications for future experiments and research will be discussed.

  20. Influence of thickness and permeability of endothelial surface layer on transmission of shear stress in capillaries

    NASA Astrophysics Data System (ADS)

    Zhang, SongPeng; Zhang, XiangJun; Tian, Yu; Meng, YongGang; Lipowsky, Herbert

    2015-07-01

    The molecular coating on the surface of microvascular endothelium has been identified as a barrier to transvascular exchange of solutes. With a thickness of hundreds of nanometers, this endothelial surface layer (ESL) has been treated as a porous domain within which fluid shear stresses are dissipated and transmitted to the solid matrix to initiate mechanotransduction events. The present study aims to examine the effects of the ESL thickness and permeability on the transmission of shear stress throughout the ESL. Our results indicate that fluid shear stresses rapidly decrease to insignificant levels within a thin transition layer near the outer boundary of the ESL with a thickness on the order of ten nanometers. The thickness of the transition zone between free fluid and the porous layer was found to be proportional to the square root of the Darcy permeability. As the permeability is reduced ten-fold, the interfacial fluid and solid matrix shear stress gradients increase exponentially two-fold. While the interfacial fluid shear stress is positively related to the ESL thickness, the transmitted matrix stress is reduced by about 50% as the ESL thickness is decreased from 500 to 100 nm, which may occur under pathological conditions. Thus, thickness and permeability of the ESL are two main factors that determine flow features and the apportionment of shear stresses between the fluid and solid phases of the ESL. These results may shed light on the mechanisms of force transmission through the ESL and the pathological events caused by alterations in thickness and permeability of the ESL.

  1. Disruption of cytoskeletal structures mediates shear stress-induced endothelin-1 gene expression in cultured porcine aortic endothelial cells.

    PubMed Central

    Morita, T; Kurihara, H; Maemura, K; Yoshizumi, M; Yazaki, Y

    1993-01-01

    Hemodynamic shear stress alters the architecture and functions of vascular endothelial cells. We have previously shown that the synthesis of endothelin-1 (ET-1) in endothelial cells is increased by exposure to shear stress. Here we examined whether shear stress-induced alterations in cytoskeletal structures are responsible for increases in ET-1 synthesis in cultured porcine aortic endothelial cells. Exposure of endothelial cells to 5 dyn/cm2 of low shear stress rapidly increased monomeric G-actin contents within 5 min without changing total actin contents. The ratio of G- to total actin, 54 +/- 0.8% in quiescent endothelial cells, increased to 87 +/- 4.2% at 6 h and then decreased. Following the disruption of filamentous (F)-actin into G-actin, ET-1 mRNA levels in endothelial cells also increased within 30 min and reached a peak at 6 h. The F-actin stabilizer, phalloidin, abolished shear stress-induced increases in ET-1 mRNA; however, it failed to inhibit increases in ET-1 mRNA secondary to other stimulants. This indicates that shear stress-induced increases in ET-1 mRNA levels may be mediated by the disruption of actin fibers. Furthermore, increases in ET-1 gene expression can be induced by actin-disrupting agents, cytochalasin B and D. Another cytoskeleton-disrupting agent, colchicine, which inhibits dimerization of tubulin, did not affect the basal level of ET-1 mRNA. However, colchicine completely inhibited shear stress- and cytochalasin B-induced increases in ET-1 mRNA levels. These results suggest that shear stress-induced ET-1 gene expression in endothelial cells is mediated by the disruption of actin cytoskeleton and this induction is dependent on the integrity of microtubules. Images PMID:8408624

  2. Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling.

    PubMed

    Franco, Claudio A; Jones, Martin L; Bernabeu, Miguel O; Vion, Anne-Clemence; Barbacena, Pedro; Fan, Jieqing; Mathivet, Thomas; Fonseca, Catarina G; Ragab, Anan; Yamaguchi, Terry P; Coveney, Peter V; Lang, Richard A; Gerhardt, Holger

    2016-02-04

    Endothelial cells respond to molecular and physical forces in development and vascular homeostasis. Deregulation of endothelial responses to flow-induced shear is believed to contribute to many aspects of cardiovascular diseases including atherosclerosis. However, how molecular signals and shear-mediated physical forces integrate to regulate vascular patterning is poorly understood. Here we show that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/Wnt11 renders endothelial cells more sensitive to shear, resulting in axial polarization and migration against flow at lower shear levels. Integration of flow modelling and polarity analysis in entire vascular networks demonstrates that polarization against flow is achieved differentially in artery, vein, capillaries and the primitive sprouting front. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus.

  3. Effect of Shear Stress on Permeability of Vascular Endothelial Monolayer Cocultured with Smooth Muscle Cells

    NASA Astrophysics Data System (ADS)

    Sakamoto, Naoya; Ohashi, Toshiro; Sato, Masaaki

    Effect of fluid shear stress on permeability of endothelial monolayer was investigated using an endothelial cell (EC)-smooth muscle cell (SMC) cocultured model (CM). Permeability of ECs to bovine serum albumin was measured after exposure to shear stress of 1.5Pa for 48 hours. Morphology and VE-cadherin expression of ECs in CM was almost same as of ECs cultured alone (monocultured model, MM). Under static condition, EC permeability was 5.1±3.0 × 10-6cm/sec (mean±SD) in MM and 6.5±3.4 × 10-6cm/sec in CM. After exposure to shear stress, EC permeability in CM (2.2±1.9 × 10-6cm/sec, p < 0.05) significantly decreased compared with the static model. However, EC permeability in MM (3.9±3.2 × 10-6cm/sec) did not significantly change compared with static cultured condition. These results suggested that cellular interactions between ECs and SMCs have important influences on EC permeability.

  4. Dynamic adhesion of umbilical cord blood endothelial progenitor cells under laminar shear stress.

    PubMed

    Angelos, Mathew G; Brown, Melissa A; Satterwhite, Lisa L; Levering, Vrad W; Shaked, Natan T; Truskey, George A

    2010-12-01

    Late outgrowth endothelial progenitor cells (EPCs) represent a promising cell source for rapid reendothelialization of damaged vasculature after expansion ex vivo and injection into the bloodstream. We characterized the dynamic adhesion of umbilical-cord-blood-derived EPCs (CB-EPCs) to surfaces coated with fibronectin. CB-EPC solution density affected the number of adherent cells and larger cells preferentially adhered at lower cell densities. The number of adherent cells varied with shear stress, with the maximum number of adherent cells and the shear stress at maximum adhesion depending upon fluid viscosity. CB-EPCs underwent limited rolling, transiently tethering for short distances before firm arrest. Immediately before arrest, the instantaneous velocity decreased independent of shear stress. A dimensional analysis indicated that adhesion was a function of the net force on the cells, the ratio of cell diffusion to sliding speed, and molecular diffusivity. Adhesion was not limited by the settling rate and was highly specific to α(5)β(1) integrin. Total internal reflection fluorescence microscopy showed that CB-EPCs produced multiple contacts of α(5)β(1) with the surface and the contact area grew during the first 20 min of attachment. These results demonstrate that CB-EPC adhesion from blood can occur under physiological levels of shear stress.

  5. The Interaction between Fluid Wall Shear Stress and Solid Circumferential Strain Affects Endothelial Gene Expression.

    PubMed

    Amaya, Ronny; Pierides, Alexis; Tarbell, John M

    2015-01-01

    Endothelial cells lining the walls of blood vessels are exposed simultaneously to wall shear stress (WSS) and circumferential stress (CS) that can be characterized by the temporal phase angle between WSS and CS (stress phase angle - SPA). Regions of the circulation with highly asynchronous hemodynamics (SPA close to -180°) such as coronary arteries are associated with the development of pathological conditions such as atherosclerosis and intimal hyperplasia whereas more synchronous regions (SPA closer to 0°) are spared of disease. The present study evaluates endothelial cell gene expression of 42 atherosclerosis-related genes under asynchronous hemodynamics (SPA=-180 °) and synchronous hemodynamics (SPA=0 °). This study used a novel bioreactor to investigate the cellular response of bovine aortic endothelial cells (BAECS) exposed to a combination of pulsatile WSS and CS at SPA=0 or SPA=-180. Using a PCR array of 42 genes, we determined that BAECS exposed to non-reversing sinusoidal WSS (10±10 dyne/cm2) and CS (4 ± 4%) over a 7 hour testing period displayed 17 genes that were up regulated by SPA = -180 °, most of them pro-atherogenic, including NFκB and other NFκB target genes. The up regulation of NFκB p50/p105 and p65 by SPA =-180° was confirmed by Western blots and immunofluorescence staining demonstrating the nuclear translocation of NFκB p50/p105 and p65. These data suggest that asynchronous hemodynamics (SPA=-180 °) can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without shear stress reversal, indicating that SPA may be an important parameter characterizing arterial susceptibility to disease.

  6. Effects of shear stress pattern and magnitude on mesenchymal transformation and invasion of aortic valve endothelial cells

    PubMed Central

    Mahler, Gretchen J.; Frendl, Christopher M.; Cao, Qingfeng; Butcher, Jonathan T.

    2015-01-01

    Understanding the role of mechanical forces on cell behavior is critical for tissue engineering, regenerative medicine, and disease initiation studies. Current hemodynamic bioreactors are largely limited to 2D substrates or the application of general flow conditions at a tissue level, which eliminates the investigation of some essential physiological and pathological responses. One example is the mesenchymal transformation of endothelial cells in response to shear stress. Endothelial to mesenchymal transformation (EndMT) is a valve morphogenic mechanism associated with aortic valve disease initiation. The aortic valve experiences oscillatory shear on the disease-susceptible fibrosa, and the role of hemodynamics on adult EndMT is unknown. The goal of this work was to develop and characterize a microfluidic bioreactor that applies physiologically relevant laminar or oscillatory shear stresses to endothelial cells and permits the quantitative analysis of 3D cell-extracellular matrix (ECM) interactions. In this study, porcine aortic valve endothelial cells were seeded onto 3D collagen I gels and exposed to different magnitudes of steady or oscillatory shear stress for 48 hours. Cells elongated and aligned perpendicular to laminar, but not oscillatory shear. Low steady shear stress (2 dyne/cm2) and oscillatory shear stress upregulated EndMT- (ACTA2, Snail, TGFB1) and inflammation- (ICAM1, NFKB1) related gene expression, EndMT-related (αSMA) protein expression, and matrix invasion when compared with static controls or cells exposed to high steady shear (10 and 20 dyne/cm2). Our system enables direct testing of the role of shear stress on endothelial cell mesenchymal transformation in a dynamic, 3D environment and shows that hemodynamics regulate EndMT in adult valve endothelial cells. PMID:24898772

  7. Effects of biaxial oscillatory shear stress on endothelial cell proliferation and morphology.

    PubMed

    Chakraborty, Amlan; Chakraborty, Sutirtha; Jala, Venkatakrishna R; Haribabu, Bodduluri; Sharp, M Keith; Berson, R Eric

    2012-03-01

    Wall shear stress (WSS) on anchored cells affects their responses, including cell proliferation and morphology. In this study, the effects of the directionality of pulsatile WSS on endothelial cell proliferation and morphology were investigated for cells grown in a Petri dish orbiting on a shaker platform. Time and location dependent WSS was determined by computational fluid dynamics (CFD). At low orbital speed (50 rpm), WSS was shown to be uniform (0-1 dyne/cm(2)) across the bottom of the dish, while at higher orbital speed (100 and 150 rpm), WSS remained fairly uniform near the center and fluctuated significantly (0-9 dyne/cm(2)) near the side walls of the dish. Since WSS on the bottom of the dish is two-dimensional, a new directional oscillatory shear index (DOSI) was developed to quantify the directionality of oscillating shear. DOSI approached zero for biaxial oscillatory shear of equal magnitudes near the center and approached one for uniaxial pulsatile shear near the wall, where large tangential WSS dominated a much smaller radial component. Near the center (low DOSI), more, smaller and less elongated cells grew, whereas larger cells with greater elongation were observed in the more uniaxial oscillatory shear (high DOSI) near the periphery of the dish. Further, cells aligned with the direction of the largest component of shear but were randomly oriented in low magnitude biaxial shear. Statistical analyses of the individual and interacting effects of multiple factors (DOSI, shear magnitudes and orbital speeds) showed that DOSI significantly affected all the responses, indicating that directionality is an important determinant of cellular responses.

  8. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress stimulates an inflammatory response

    NASA Technical Reports Server (NTRS)

    Sorescu, George P.; Sykes, Michelle; Weiss, Daiana; Platt, Manu O.; Saha, Aniket; Hwang, Jinah; Boyd, Nolan; Boo, Yong C.; Vega, J. David; Taylor, W. Robert; Jo, Hanjoong

    2003-01-01

    Atherosclerosis is now viewed as an inflammatory disease occurring preferentially in arterial regions exposed to disturbed flow conditions, including oscillatory shear stress (OS), in branched arteries. In contrast, the arterial regions exposed to laminar shear (LS) are relatively lesion-free. The mechanisms underlying the opposite effects of OS and LS on the inflammatory and atherogenic processes are not clearly understood. Here, through DNA microarrays, protein expression, and functional studies, we identify bone morphogenic protein 4 (BMP4) as a mechanosensitive and pro-inflammatory gene product. Exposing endothelial cells to OS increased BMP4 protein expression, whereas LS decreased it. In addition, we found BMP4 expression only in the selective patches of endothelial cells overlying foam cell lesions in human coronary arteries. The same endothelial patches also expressed higher levels of intercellular cell adhesion molecule-1 (ICAM-1) protein compared with those of non-diseased areas. Functionally, we show that OS and BMP4 induced ICAM-1 expression and monocyte adhesion by a NFkappaB-dependent mechanism. We suggest that BMP4 is a mechanosensitive, inflammatory factor playing a critical role in early steps of atherogenesis in the lesion-prone areas.

  9. Effects of shear stress on endothelial cells: go with the flow.

    PubMed

    Chistiakov, D A; Orekhov, A N; Bobryshev, Y V

    2017-02-01

    Haemodynamic forces influence the functional properties of vascular endothelium. Endothelial cells (ECs) have a variety of receptors, which sense flow and transmit mechanical signals through mechanosensitive signalling pathways to recipient molecules that lead to phenotypic and functional changes. Arterial architecture varies greatly exhibiting bifurcations, branch points and curved regions, which are exposed to various flow patterns. Clinical studies showed that atherosclerotic plaques develop preferentially at arterial branches and curvatures, that is in the regions exposed to disturbed flow and shear stress. In the atheroprone regions, the endothelium has a proinflammatory phenotype associated with low nitric oxide production, reduced barrier function and increased proadhesive, procoagulant and proproliferative properties. Atheroresistant regions are exposed to laminar flow and high shear stress that induce prosurvival antioxidant signals and maintain the quiescent phenotype in ECs. Indeed, various flow patterns contribute to phenotypic and functional heterogeneity of arterial endothelium whose response to proatherogenic stimuli is differentiated. This may explain the preferential development of endothelial dysfunction in arterial sites with disturbed flow.

  10. Suppression of TAK1 pathway by shear stress counteracts the inflammatory endothelial cell phenotype induced by oxidative stress and TGF-β1

    PubMed Central

    Lee, Ee Soo; Boldo, Llorenç Solé; Fernandez, Bernadette O.; Feelisch, Martin; Harmsen, Martin C.

    2017-01-01

    Endothelial dysfunction is characterised by aberrant redox signalling and an inflammatory phenotype. Shear stress antagonises endothelial dysfunction by increasing nitric oxide formation, activating anti-inflammatory pathways and suppressing inflammatory pathways. The TAK1 (MAP3K7) is a key mediator of inflammation and non-canonical TGF-β signalling. While the individual roles of TAK1, ERK5 (MAPK7) and TGF-β pathways in endothelial cell regulation are well characterised, an integrative understanding of the orchestration of these pathways and their crosstalk with the redox system under shear stress is lacking. We hypothesised that shear stress counteracts the inflammatory effects of oxidative stress and TGF-β1 on endothelial cells by restoring redox balance and repressing the TAK1 pathway. Using human umbilical vein endothelial cells, we here show that TGF-β1 aggravates oxidative stress-mediated inflammatory activation and that shear stress activates ERK5 signalling while attenuating TGF-β signalling. ERK5 activation restores redox balance, but fails to repress the inflammatory effect of TGF-β1 which is suppressed upon TAK1 inhibition. In conclusion, shear stress counteracts endothelial dysfunction by suppressing the pro-inflammatory non-canonical TGF-β pathway and by activating the ERK5 pathway which restores redox signalling. We propose that a pharmacological compound that abates TGF-β signalling and enhances ERK5 signalling may be useful to counteract endothelial dysfunction. PMID:28209993

  11. Mis-sizing of stent promotes intimal hyperplasia: impact of endothelial shear and intramural stress.

    PubMed

    Chen, Henry Y; Sinha, Anjan K; Choy, Jenny S; Zheng, Hai; Sturek, Michael; Bigelow, Brian; Bhatt, Deepak L; Kassab, Ghassan S

    2011-12-01

    Stent can cause flow disturbances on the endothelium and compliance mismatch and increased stress on the vessel wall. These effects can cause low wall shear stress (WSS), high wall shear stress gradient (WSSG), oscillatory shear index (OSI), and circumferential wall stress (CWS), which may promote neointimal hyperplasia (IH). The hypothesis is that stent-induced abnormal fluid and solid mechanics contribute to IH. To vary the range of WSS, WSSG, OSI, and CWS, we intentionally mismatched the size of stents to that of the vessel lumen. Stents were implanted in coronary arteries of 10 swine. Intravascular ultrasound (IVUS) was used to size the coronary arteries and stents. After 4 wk of stent implantation, IVUS was performed again to determine the extent of IH. In conjunction, computational models of actual stents, the artery, and non-Newtonian blood were created in a computer simulation to yield the distribution of WSS, WSSG, OSI, and CWS in the stented vessel wall. An inverse relation (R(2) = 0.59, P < 0.005) between WSS and IH was found based on a linear regression analysis. Linear relations between WSSG, OSI, and IH were observed (R(2) = 0.48 and 0.50, respectively, P < 0.005). A linear relation (R(2) = 0.58, P < 0.005) between CWS and IH was also found. More statistically significant linear relations between the ratio of CWS to WSS (CWS/WSS), the products CWS × WSSG and CWS × OSI, and IH were observed (R(2) = 0.67, 0.54, and 0.56, respectively, P < 0.005), suggesting that both fluid and solid mechanics influence the extent of IH. Stents create endothelial flow disturbances and intramural wall stress concentrations, which correlate with the extent of IH formation, and these effects were exaggerated with mismatch of stent/vessel size. These findings reveal the importance of reliable vessel and stent sizing to improve the mechanics on the vessel wall and minimize IH.

  12. Laminar shear stress up-regulates peroxiredoxins (PRX) in endothelial cells: PRX 1 as a mechanosensitive antioxidant.

    PubMed

    Mowbray, Amy L; Kang, Dong-Hoon; Rhee, Sue Goo; Kang, Sang Won; Jo, Hanjoong

    2008-01-18

    Shear stress plays a significant role in endothelial cell biology and atherosclerosis development. Previous work by our group has shown that fluid flow stimulates important functional changes in cells through protein expression regulation. Peroxiredoxins (PRX) are a family of antioxidant enzymes but have yet to be investigated in response to shear stress. Studies have shown that oscillatory shear stress (OS) increases reactive oxygen species (ROS) levels in endothelial cells, whereas laminar shear stress (LS) blocks this response. We hypothesized that PRX are responsible for the anti-oxidative effect of LS. To test this hypothesis, bovine aortic endothelial cells (BAEC) were subjected to LS (15 dyn/cm(2)), OS (+/-5 dyn/cm(2), 1 Hz), or static conditions for 24 h. Using Western blot and immunofluorescence staining, all six isoforms of PRX were identified in BAEC. When compared with OS and static, exposure to chronic LS up-regulated PRX 1 levels intracellularly. LS also increased expression of PRX 5 relative to static controls, but not OS. PRX exhibited broad subcellular localization, with distribution in the cytoplasm, Golgi, mitochondria, and intermediate filaments. In addition, PRX 1 knock down, using specific small interference RNA, attenuated LS-dependent reactive oxygen species reduction in BAEC. However, PRX 5 depletion did not. Together, these results suggest that PRX 1 is a novel mechanosensitive antioxidant, playing an important role in shear-dependent regulation of endothelial biology and atherosclerosis.

  13. Non-canonical Wnt signalling modulates the endothelial shear stress flow sensor in vascular remodelling

    PubMed Central

    Franco, Claudio A; Jones, Martin L; Bernabeu, Miguel O; Vion, Anne-Clemence; Barbacena, Pedro; Fan, Jieqing; Mathivet, Thomas; Fonseca, Catarina G; Ragab, Anan; Yamaguchi, Terry P; Coveney, Peter V; Lang, Richard A; Gerhardt, Holger

    2016-01-01

    Endothelial cells respond to molecular and physical forces in development and vascular homeostasis. Deregulation of endothelial responses to flow-induced shear is believed to contribute to many aspects of cardiovascular diseases including atherosclerosis. However, how molecular signals and shear-mediated physical forces integrate to regulate vascular patterning is poorly understood. Here we show that endothelial non-canonical Wnt signalling regulates endothelial sensitivity to shear forces. Loss of Wnt5a/Wnt11 renders endothelial cells more sensitive to shear, resulting in axial polarization and migration against flow at lower shear levels. Integration of flow modelling and polarity analysis in entire vascular networks demonstrates that polarization against flow is achieved differentially in artery, vein, capillaries and the primitive sprouting front. Collectively our data suggest that non-canonical Wnt signalling stabilizes forming vascular networks by reducing endothelial shear sensitivity, thus keeping vessels open under low flow conditions that prevail in the primitive plexus. DOI: http://dx.doi.org/10.7554/eLife.07727.001 PMID:26845523

  14. Flow shear stress regulates endothelial barrier function and expression of angiogenic factors in a 3D microfluidic tumor vascular model

    PubMed Central

    Buchanan, Cara F; Verbridge, Scott S; Vlachos, Pavlos P; Rylander, Marissa Nichole

    2014-01-01

    Endothelial cells lining blood vessels are exposed to various hemodynamic forces associated with blood flow. These include fluid shear, the tangential force derived from the friction of blood flowing across the luminal cell surface, tensile stress due to deformation of the vessel wall by transvascular flow, and normal stress caused by the hydrodynamic pressure differential across the vessel wall. While it is well known that these fluid forces induce changes in endothelial morphology, cytoskeletal remodeling, and altered gene expression, the effect of flow on endothelial organization within the context of the tumor microenvironment is largely unknown. Using a previously established microfluidic tumor vascular model, the objective of this study was to investigate the effect of normal (4 dyn/cm2), low (1 dyn/cm2), and high (10 dyn/cm2) microvascular wall shear stress (WSS) on tumor-endothelial paracrine signaling associated with angiogenesis. It is hypothesized that high WSS will alter the endothelial phenotype such that vascular permeability and tumor-expressed angiogenic factors are reduced. Results demonstrate that endothelial permeability decreases as a function of increasing WSS, while co-culture with tumor cells increases permeability relative to mono-cultures. This response is likely due to shear stress-mediated endothelial cell alignment and tumor-VEGF-induced permeability. In addition, gene expression analysis revealed that high WSS (10 dyn/cm2) significantly down-regulates tumor-expressed MMP9, HIF1, VEGFA, ANG1, and ANG2, all of which are important factors implicated in tumor angiogenesis. This result was not observed in tumor mono-cultures or static conditioned media experiments, suggesting a flow-mediated paracrine signaling mechanism exists with surrounding tumor cells that elicits a change in expression of angiogenic factors. Findings from this work have significant implications regarding low blood velocities commonly seen in the tumor vasculature

  15. Endothelial cell alignment as a result of anisotropic strain and flow induced shear stress combinations.

    PubMed

    Sinha, Ravi; Le Gac, Séverine; Verdonschot, Nico; van den Berg, Albert; Koopman, Bart; Rouwkema, Jeroen

    2016-07-12

    Endothelial cells (ECs) are continuously exposed in vivo to cyclic strain and shear stress from pulsatile blood flow. When these stimuli are applied in vitro, ECs adopt an appearance resembling their in vivo state, most apparent in their alignment (perpendicular to uniaxial strain and along the flow). Uniaxial strain and flow perpendicular to the strain, used in most in vitro studies, only represent the in vivo conditions in straight parts of vessels. The conditions present over large fractions of the vasculature can be better represented by anisotropic biaxial strains at various orientations to flow. To emulate these biological complexities in vitro, we have developed a medium-throughput device to screen for the effects on cells of variously oriented anisotropic biaxial strains and flow combinations. Upon the application of only strains for 24 h, ECs (HUVECs) aligned perpendicular to the maximum principal strain and the alignment was stronger for a higher maximum:minimum principal strain ratio. A 0.55 Pa shear stress, when applied alone or with strain for 24 h, caused cells to align along the flow. Studying EC response to such combined physiological mechanical stimuli was not possible with existing platforms and to our best knowledge, has not been reported before.

  16. Endothelial cell alignment as a result of anisotropic strain and flow induced shear stress combinations

    PubMed Central

    Sinha, Ravi; Le Gac, Séverine; Verdonschot, Nico; van den Berg, Albert; Koopman, Bart; Rouwkema, Jeroen

    2016-01-01

    Endothelial cells (ECs) are continuously exposed in vivo to cyclic strain and shear stress from pulsatile blood flow. When these stimuli are applied in vitro, ECs adopt an appearance resembling their in vivo state, most apparent in their alignment (perpendicular to uniaxial strain and along the flow). Uniaxial strain and flow perpendicular to the strain, used in most in vitro studies, only represent the in vivo conditions in straight parts of vessels. The conditions present over large fractions of the vasculature can be better represented by anisotropic biaxial strains at various orientations to flow. To emulate these biological complexities in vitro, we have developed a medium-throughput device to screen for the effects on cells of variously oriented anisotropic biaxial strains and flow combinations. Upon the application of only strains for 24 h, ECs (HUVECs) aligned perpendicular to the maximum principal strain and the alignment was stronger for a higher maximum:minimum principal strain ratio. A 0.55 Pa shear stress, when applied alone or with strain for 24 h, caused cells to align along the flow. Studying EC response to such combined physiological mechanical stimuli was not possible with existing platforms and to our best knowledge, has not been reported before. PMID:27404382

  17. LDL decreases the membrane compliance and cell adhesion of endothelial cells under fluid shear stress.

    PubMed

    Wei, Dangheng; Chen, Yongpeng; Tang, Chaojun; Huang, Hua; Liu, Lushan; Wang, Zuo; Li, Ruming; Wang, Guixue

    2013-03-01

    Atherosclerosis is an inflammatory disease of large and medium sized arteriole walls that is precipitated by elevated levels of low-density lipoprotein (LDL) cholesterol in the blood. However, the mechanisms that lead to the initiation of atherosclerosis are not fully understood. In this study, endothelial cells (ECs) were incubated with LDL for 24 h, and then the lipid was detected with Oil Red O staining and cholesterol ester was assayed with high-performance liquid chromatography (HPLC). F-actin was examined by fluorescence microscopy and the viscoelasticity of ECs was investigated using the micropipette aspiration technique. Then, a parallel-plate flow chamber device was used to observe the adhesion and retention of ECs under shear stress. The results demonstrated that elevated LDL significantly increased the cellular lipid content and induced the rearrangement of cytoskeletal F-actin. The initial rapid deformability (l/K 1 + l/K 2) was reduced by elevated cellular LDL levels, while membrane viscosity (μ) was increased by LDL accumulation. After treatment with 150 mg L(-1) LDL for 24 h, the adhesion of ECs under fluid shear stress was significantly decreased (p < 0.05). These results suggested that LDL induced cellular lipid accumulation and cytoskeleton reorganization which increased the cellular stiffness and decreased the adhesion of ECs.

  18. Hydrostatic pressure and shear stress affect endothelin-1 and nitric oxide release by endothelial cells in bioreactors.

    PubMed

    Vozzi, Federico; Bianchi, Francesca; Ahluwalia, Arti; Domenici, Claudio

    2014-01-01

    Abundant experimental evidence demonstrates that endothelial cells are sensitive to flow; however, the effect of fluid pressure or pressure gradients that are used to drive viscous flow is not well understood. There are two principal physical forces exerted on the blood vessel wall by the passage of intra-luminal blood: pressure and shear. To analyze the effects of pressure and shear independently, these two stresses were applied to cultured cells in two different types of bioreactors: a pressure-controlled bioreactor and a laminar flow bioreactor, in which controlled levels of pressure or shear stress, respectively, can be generated. Using these bioreactor systems, endothelin-1 (ET-1) and nitric oxide (NO) release from human umbilical vein endothelial cells were measured under various shear stress and pressure conditions. Compared to the controls, a decrease of ET-1 production by the cells cultured in both bioreactors was observed, whereas NO synthesis was up-regulated in cells under shear stress, but was not modulated by hydrostatic pressure. These results show that the two hemodynamic forces acting on blood vessels affect endothelial cell function in different ways, and that both should be considered when planning in vitro experiments in the presence of flow. Understanding the individual and synergic effects of the two forces could provide important insights into physiological and pathological processes involved in vascular remodeling and adaptation.

  19. [Comparison of adhesion of different endothelial cells under shear stress load in the flow field in vitro].

    PubMed

    Xiao, Zhenghua; Zhang, Bengui; Zhang, Eryong; Xu, Weilin; Shi, Yingkang; Guo, Yingqiang

    2011-02-01

    This study was aimed to compare the differences of adhesion properties of endothelial cells (EC) from arteries (AEC), veins (VEC) and capillaries (MVEC) under shear stress condition, and to explore whether they can get the same adhesive ability as graft in similar shear stress conditions. With mended parallel plate flow apparatus and peristalsis pump providing fluid shear stress used, endothelial culture models were established in vitro with the same environmental factors as steady culture. To compare the adhesion among three kinds of endothelial cells under dynamic condition and static condition, the dynamic change of cytoskeletal actin filaments and the effects of different adhesive proteins coated on the adhesion of EC to the glass were studied. The cultured endothelial cells under flow conditions were extended and arranged along the direction of flow. The adhesive ability from high to low under static condition were AEC, MVEC and VEC (VEC compared with AEC or MVEC, P < 0.05), sequentially. The adhesion of endothelial cells from variety sources under dynamic culture condition was significantly increased than that of the static groups. The ratio of cell retention was not significantly different between AEC and MVEC. But VEC was significantly different (P < 0.05) compared with AEC or MVEC. The actin filaments (F-actin) were bundled together and arranged along the direction of flow after fluid culture. Dense peripheral band (DPB) gradually disappeared and distinct stress fibers were formed, which even interconnected to form a whole in the MVEC. The adhesion of AEC, VEC and MVEC under shear stress conditions are more significantly increased than those under the static culture conditions, and the MVEC can achieve the same adhesion as AEC.

  20. Finite-Element Stress Analysis of a Multicomponent Model of Sheared and Focally-Adhered Endothelial Cells

    PubMed Central

    Ferko, Michael C.; Bhatnagar, Amit; Garcia, Mariana B.; Butler, Peter J.

    2011-01-01

    Hemodynamic forces applied at the apical surface of vascular endothelial cells may be redistributed to and amplified at remote intracellular organelles and protein complexes where they are transduced to biochemical signals. In this study we sought to quantify the effects of cellular material inhomogeneities and discrete attachment points on intracellular stresses resulting from physiological fluid flow. Steady-state shear- and magnetic bead-induced stress, strain, and displacement distributions were determined from finite-element stress analysis of a cell-specific, multicomponent elastic continuum model developed from multimodal fluorescence images of confluent endothelial cell (EC) monolayers and their nuclei. Focal adhesion locations and areas were determined from quantitative total internal reflection fluorescence microscopy and verified using green fluorescence protein–focal adhesion kinase (GFP–FAK). The model predicts that shear stress induces small heterogeneous deformations of the endothelial cell cytoplasm on the order of <100 nm. However, strain and stress were amplified 10–100-fold over apical values in and around the high-modulus nucleus and near focal adhesions (FAs) and stress distributions depended on flow direction. The presence of a 0.4 μm glycocalyx was predicted to increase intracellular stresses by ~2-fold. The model of magnetic bead twisting rheometry also predicted heterogeneous stress, strain, and displacement fields resulting from material heterogeneities and FAs. Thus, large differences in moduli between the nucleus and cytoplasm and the juxtaposition of constrained regions (e.g. FAs) and unattached regions provide two mechanisms of stress amplification in sheared endothelial cells. Such phenomena may play a role in subcellular localization of early mechanotransduction events. PMID:17160699

  1. A model for studying the effect of shear stress on interactions between vascular endothelial cells and smooth muscle cells.

    PubMed

    Chiu, Jeng-Jiann; Chen, Li-Jing; Chen, Cheng-Nan; Lee, Pei-Ling; Lee, Chih-I

    2004-04-01

    Vascular endothelial cells (ECs) are constantly subjected to blood flow-induced shear stress and the influences of neighboring smooth muscle cells (SMCs). In the present study, a coculture flow system was developed to study the effect of shear stress on EC-SMC interactions. ECs and SMCs were separated by a porous membrane with only the EC side subjected to the flow condition. When ECs were exposed to a shear stress of 12 dynes/cm2 for 24 h, the cocultured SMCs tended to orient perpendicularly to the flow direction. This perpendicular orientation of the cocultured SMCs to flow direction was not observed when ECs were exposed to a shear stress of 2 dynes/cm2. Under the static condition, long and parallel actin bundles were observed in the central regions of the cocultured SMCs, whereas the actin filaments localized mainly at the periphery of the cocultured ECs. After 24 h of flow application, the cocultured ECs displayed very long, well-organized, parallel actin stress fibers aligned with the flow direction in the central regions of the cells. Immunostaining of platelet endothelial cell adhesion molecule-1 confirmed the elongation and alignment of the cocultured ECs with the flow direction. Coculture with SMCs under static condition induced EC gene expressions of growth-related oncogene-alpha and monocyte chemotactic protein-1, and shear stress was found to abolish these SMC-induced gene expressions. Our results suggest that shear stress may serve as a down-regulator for the pathophysiologically relevant gene expression in ECs cocultured with SMCs.

  2. Mathematical Model for Shear Stress Dependent NO and Adenine Nucleotide Production from Endothelial Cells

    PubMed Central

    Kirby, Patrick; Buerk, Donald G.; Parikh, Jaimit; Barbee, Kenneth A.; Jaron, Dov

    2015-01-01

    We developed a mass transport model for a parallel-plate flow chamber apparatus to predict the concentrations of nitric oxide (NO) and adenine nucleotides (ATP, ADP) produced by cultured endothelial cells (ECs) and investigated how the net rates of production, degradation, and mass transport for these three chemical species vary with changes in wall shear stress (τw). These simulations provide an improved understanding of experimental results obtained with parallel-plate flow chambers and allows quantitative analysis of the relationship between τw, adenine nucleotide concentrations, and NO produced by ECs. Experimental data obtained after altering ATP and ADP concentrations with apyrase were analyzed to quantify changes in the rate of NO production (RNO). The effects of different isoforms of apyrase on ATP and ADP concentrations and nucleotide-dependent changes in RNO could be predicted with the model. A decrease in ATP was predicted with apyrase, but an increase in ADP was simulated due to degradation of ATP. We found that a simple proportional relationship relating a component of RNO to the sum of ATP and ADP provided a close match to the fitted curve for experimentally measured changes in RNO with apyrase. Estimates for the proportionality constant ranged from 0.0067 to 0.0321 μM/s increase in RNO per nM nucleotide concentration, depending on which isoform of apyrase was modeled, with the largest effect of nucleotides on RNO at low τw (< 6 dyn/cm2). PMID:26529478

  3. Visualization of Simulated Endothelial Shear Stress and Blood Flow in Coronary Arteries

    NASA Astrophysics Data System (ADS)

    Borkin, Michelle; Feldman, Charles L.; Pfister, Hanspeter; Melchionna, Simone; Kaxiras, Efthimios

    2010-11-01

    Low endothelial shear stress (ESS) identifies areas of atherosclerotic disease lesion formation in the coronary arteries. However, it is impossible to directly measure ESS in vivo for an entire arterial tree. As part of the Multiscale Hemodynamics Project, computed tomography angiography (CTA) data is being used to obtain patient specific heart and coronary system geometries and then MUPHY, a multi-physics and multi-scale simulation code combining microscopic Molecular Dynamics (MD) with a hydro-kinetic Lattice Boltzmann (LB) method, is applied in order to simulate blood flow through the coronary arteries. Having effective visualizations of the simulation's multidimensional output, including ESS, is vital for the quick and thorough non-invasive evaluation of the patient. To this end, we have developed new visualization tools and techniques to make the simulation's output useful in a clinical diagnostic setting, examined the effectiveness of 2D versus 3D representations, and explored blood flow representations. The visualization methods developed are also applicable to other areas of fluid dynamics.

  4. MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activity

    SciTech Connect

    Weber, Martina; Baker, Meredith B.; Moore, Jeffrey P.; Searles, Charles D.

    2010-03-19

    Mechanical forces associated with blood flow play an important role in regulating vascular signaling and gene expression in endothelial cells (ECs). MicroRNAs (miRNAs) are a class of noncoding RNAs that posttranscriptionally regulate the expression of genes involved in diverse cell functions, including differentiation, growth, proliferation, and apoptosis. miRNAs are known to have an important role in modulating EC biology, but their expression and functions in cells subjected to shear stress conditions are unknown. We sought to determine the miRNA expression profile in human ECs subjected to unidirectional shear stress and define the role of miR-21 in shear stress-induced changes in EC function. TLDA array and qRT-PCR analysis performed on HUVECs exposed to prolonged unidirectional shear stress (USS, 24 h, 15 dynes/cm{sup 2}) identified 13 miRNAs whose expression was significantly upregulated (p < 0.05). The miRNA with the greatest change was miR-21; it was increased 5.2-fold (p = 0.002) in USS-treated versus control cells. Western analysis demonstrated that PTEN, a known target of miR-21, was downregulated in HUVECs exposed to USS or transfected with pre-miR-21. Importantly, HUVECs overexpressing miR-21 had decreased apoptosis and increased eNOS phosphorylation and nitric oxide (NO{sup {center_dot}}) production. These data demonstrate that shear stress forces regulate the expression of miRNAs in ECs, and that miR-21 influences endothelial biology by decreasing apoptosis and activating the NO{sup {center_dot}} pathway. These studies advance our understanding of the mechanisms by which shear stress forces modulate vascular homeostasis.

  5. Atrial fibrillation pacing decreases intravascular shear stress in a New Zealand white rabbit model: implications in endothelial function.

    PubMed

    Jen, Nelson; Yu, Fei; Lee, Juhyun; Wasmund, Steve; Dai, Xiaohu; Chen, Christina; Chawareeyawong, Pai; Yang, Yongmo; Li, Rongsong; Hamdan, Mohamed H; Hsiai, Tzung K

    2013-08-01

    Atrial fibrillation (AF) is characterized by multiple rapid and irregular atrial depolarization, leading to rapid ventricular responses exceeding 100 beats per minute (bpm). We hypothesized that rapid and irregular pacing reduced intravascular shear stress (ISS) with implication to modulating endothelial responses. To simulate AF, we paced the left atrial appendage of New Zealand White rabbits (n = 4) at rapid and irregular intervals. Surface electrical cardiograms were recorded for atrial and ventricular rhythm, and intravascular convective heat transfer was measured by microthermal sensors, from which ISS was inferred. Rapid and irregular pacing decreased arterial systolic and diastolic pressures (baseline, 99/75 mmHg; rapid regular pacing, 92/73; rapid irregular pacing, 90/68; p < 0.001, n = 4), temporal gradients ([Formula: see text] from 1,275 ± 80 to 1,056 ± 180 dyne/cm(2) s), and reduced ISS (from baseline at 32.0 ± 2.4 to 22.7 ± 3.5 dyne/cm(2)). Computational fluid dynamics code demonstrated that experimentally inferred ISS provided a close approximation to the computed wall shear stress at a given catheter to vessel diameter ratio, shear stress range, and catheter position. In an in vitro flow system in which time-averaged shear stress was maintained at [Formula: see text] , we further demonstrated that rapid pulse rates at 150 bpm down-regulated endothelial nitric oxide, promoted superoxide (O 2 (.-) ) production, and increased monocyte binding to endothelial cells. These findings suggest that rapid pacing reduces ISS and [Formula: see text] , and rapid pulse rates modulate endothelial responses.

  6. Integration of basal topographic cues and apical shear stress in vascular endothelial cells.

    PubMed

    Morgan, Joshua T; Wood, Joshua A; Shah, Nihar M; Hughbanks, Marissa L; Russell, Paul; Barakat, Abdul I; Murphy, Christopher J

    2012-06-01

    In vivo, vascular endothelial cells (VECs) are anchored to the underlying stroma through a specialization of the extracellular matrix, the basement membrane (BM) which provides a variety of substratum associated biophysical cues that have been shown to regulate fundamental VEC behaviors. VEC function and homeostasis are also influenced by hemodynamic cues applied to their apical surface. How the combination of these biophysical cues impacts fundamental VEC behavior remains poorly studied. In the present study, we investigated the impact of providing biophysical cues simultaneously to the basal and apical surfaces of human aortic endothelial cells (HAECs). Anisotropically ordered patterned surfaces of alternating ridges and grooves and isotropic holed surfaces of varying pitch (pitch = ridge or hole width + intervening groove or planar regions) were fabricated and seeded with HAECs. The cells were then subjected to a steady shear stress of 20 dyne/cm(2) applied either parallel or perpendicular to the direction of the ridge/groove topography. HAECs subjected to flow parallel to the ridge/groove topography exhibited protagonistic effects of the two stimuli on cellular orientation and elongation. In contrast, flow perpendicular to the substrate topography resulted in largely antagonistic effects. Interestingly, the behavior depended on the shape and size of the topographic features. HAECs exhibited a response that was less influenced by the substratum and primarily driven by flow on isotropically ordered holed surfaces of identical pitch to the anistropically ordered surfaces of alternating ridges and grooves. Simultaneous presentation of biophysical cues to the basal and apical aspects of cells also influenced nuclear orientation and elongation; however, the extent of nuclear realignment was more modest in comparison to cellular realignment regardless of the surface order of topographic features. Flow-induced HAEC migration was also influenced by the ridge

  7. Direct, real-time measurement of shear stress-induced nitric oxide produced from endothelial cells in vitro.

    PubMed

    Andrews, Allison M; Jaron, Dov; Buerk, Donald G; Kirby, Patrick L; Barbee, Kenneth A

    2010-12-15

    Nitric oxide (NO) produced by the endothelium is involved in the regulation of vascular tone. Decreased NO production or availability has been linked to endothelial dysfunction in hypercholesterolemia and hypertension. Shear stress-induced NO release is a well-established phenomenon, yet the cellular mechanisms of this response are not completely understood. Experimental limitations have hindered direct, real-time measurements of NO under flow conditions. We have overcome these challenges with a new design for a parallel-plate flow chamber. The chamber consists of two compartments, separated by a Transwell® membrane, which isolates a NO recording electrode located in the upper compartment from flow effects. Endothelial cells are grown on the bottom of the membrane, which is inserted into the chamber flush with the upper plate. We demonstrate for the first time direct real-time NO measurements from endothelial cells with controlled variations in shear stress. Step changes in shear stress from 0.1 dyn/cm(2) to 6, 10, or 20 dyn/cm(2) elicited a transient decrease in NO followed by an increase to a new steady state. An analysis of NO transport suggests that the initial decrease is due to the increased removal rate by convection as flow increases. Furthermore, the rate at which the NO concentration approaches the new steady state is related to the time-dependent cellular response rather than transport limitations of the measurement configuration. Our design offers a method for studying the kinetics of the signaling mechanisms linking NO production with shear stress as well as pathological conditions involving changes in NO production or availability.

  8. Modeling of [Formula: see text]-mediated calcium signaling in vascular endothelial cells induced by fluid shear stress and ATP.

    PubMed

    Li, Long-Fei; Xiang, Cheng; Qin, Kai-Rong

    2015-10-01

    The calcium signaling plays a vital role in flow-dependent vascular endothelial cell (VEC) physiology. Variations in fluid shear stress and ATP concentration in blood vessels can activate dynamic responses of cytosolic-free [Formula: see text] through various calcium channels on the plasma membrane. In this paper, a novel dynamic model has been proposed for transient receptor potential vanilloid 4 [Formula: see text]-mediated intracellular calcium dynamics in VECs induced by fluid shear stress and ATP. Our model includes [Formula: see text] signaling pathways through P2Y receptors and [Formula: see text] channels (indirect mechanism) and captures the roles of the [Formula: see text] compound channels in VEC [Formula: see text] signaling in response to fluid shear stress (direct mechanism). In particular, it takes into account that the [Formula: see text] compound channels are regulated by intracellular [Formula: see text] and [Formula: see text] concentrations. The simulation studies have demonstrated that the dynamic responses of calcium concentration produced by the proposed model correlate well with the existing experimental observations. We also conclude from the simulation studies that endogenously released ATP may play an insignificant role in the process of intracellular [Formula: see text] response to shear stress.

  9. Effect of shear stress on platelet adhesion to expanded polytetrafluoroethylene, a silicone sheet, and an endothelial cell monolayer.

    PubMed

    Furukawa, K S; Ushida, T; Sugano, H; Tamaki, T; Ohshima, N; Tateishi, T

    2000-01-01

    We visualized in real-time platelets adhering to the surface of three representative biomaterials, by using an apparatus consisting of a modified cone and plate rheometer combined with an upright epifluorescence microscope under two shear flows (0.1 and 5.0 dyne/cm2). The materials were expanded polytetrafluoroethylene (ePTFE), silicone sheet, and a monolayer of bovine endothelial cells (ECs) formed on glass, all of which are opaque materials used for artificial blood vessels and medical devices. According to quantitative analysis, the monolayer of ECs formed on glass had better blood compatibility than did either the ePTFE or the silicone sheet under shear flow conditions. Under a shear flow condition of 0.1 dyne/cm2, platelet adhesion was silicone sheet > ePTFE. In contrast, under a shear flow condition of 5.0 dyne/cm2, ePTFE > silicone sheet. These results indicate that the intensity of shear stress could modify the order of hemocompatibility of the materials. Therefore, direct observation of platelet adhesion under shear flow conditions is indispensable for testing and screening biomaterials and for providing a precise quantitative evaluation of platelet adhesion.

  10. Interaction between the Stress Phase Angle (SPA) and the Oscillatory Shear Index (OSI) Affects Endothelial Cell Gene Expression

    PubMed Central

    Amaya, Ronny; Cancel, Limary M.; Tarbell, John M.

    2016-01-01

    Hemodynamic forces play an important role in the non-uniform distribution of atherosclerotic lesions. Endothelial cells are exposed simultaneously to fluid wall shear stress (WSS) and solid circumferential stress (CS). Due to variations in impedance (global factors) and geometric complexities (local factors) in the arterial circulation a time lag arises between these two forces that can be characterized by the temporal phase angle between CS and WSS (stress phase angle–SPA). Asynchronous flows (SPA close to -180°) that are most prominent in coronary arteries have been associated with localization of atherosclerosis. Reversing oscillatory flows characterized by an oscillatory shear index (OSI) that is great than zero are also associated with atherosclerosis localization. In this study we examined the relationship between asynchronous flows and reversing flows in altering the expression of 37 genes relevant to atherosclerosis development. In the case of reversing oscillatory flow, we observed that the asynchronous condition upregulated 8 genes compared to synchronous hemodynamics, most of them proatherogenic. Upregulation of the pro-inflammatory transcription factor NFκB p65 was confirmed by western blot, and nuclear translocation of NFκB p65 was confirmed by immunofluorescence staining. A comparative study between non-reversing flow and reversing flow found that in the case of synchronous hemodynamics, reversing flow altered the expression of 11 genes, while in the case of asynchronous hemodynamics, reversing flow altered the expression of 17 genes. Reversing flow significantly upregulated protein expression of NFκB p65 for both synchronous and asynchronous conditions. Nuclear translocation of NFκB p65 was confirmed for synchronous and asynchronous conditions in the presence of flow reversal. These data suggest that asynchronous hemodynamics and reversing flow can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics

  11. Interaction between the Stress Phase Angle (SPA) and the Oscillatory Shear Index (OSI) Affects Endothelial Cell Gene Expression.

    PubMed

    Amaya, Ronny; Cancel, Limary M; Tarbell, John M

    2016-01-01

    Hemodynamic forces play an important role in the non-uniform distribution of atherosclerotic lesions. Endothelial cells are exposed simultaneously to fluid wall shear stress (WSS) and solid circumferential stress (CS). Due to variations in impedance (global factors) and geometric complexities (local factors) in the arterial circulation a time lag arises between these two forces that can be characterized by the temporal phase angle between CS and WSS (stress phase angle-SPA). Asynchronous flows (SPA close to -180°) that are most prominent in coronary arteries have been associated with localization of atherosclerosis. Reversing oscillatory flows characterized by an oscillatory shear index (OSI) that is great than zero are also associated with atherosclerosis localization. In this study we examined the relationship between asynchronous flows and reversing flows in altering the expression of 37 genes relevant to atherosclerosis development. In the case of reversing oscillatory flow, we observed that the asynchronous condition upregulated 8 genes compared to synchronous hemodynamics, most of them proatherogenic. Upregulation of the pro-inflammatory transcription factor NFκB p65 was confirmed by western blot, and nuclear translocation of NFκB p65 was confirmed by immunofluorescence staining. A comparative study between non-reversing flow and reversing flow found that in the case of synchronous hemodynamics, reversing flow altered the expression of 11 genes, while in the case of asynchronous hemodynamics, reversing flow altered the expression of 17 genes. Reversing flow significantly upregulated protein expression of NFκB p65 for both synchronous and asynchronous conditions. Nuclear translocation of NFκB p65 was confirmed for synchronous and asynchronous conditions in the presence of flow reversal. These data suggest that asynchronous hemodynamics and reversing flow can elicit proatherogenic responses in endothelial cells compared to synchronous hemodynamics without

  12. p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress-induced angiogenesis.

    PubMed

    Gee, Eric; Milkiewicz, Malgorzata; Haas, Tara L

    2010-01-01

    Increased capillary shear stress induces angiogenesis in skeletal muscle, but the signaling mechanisms underlying this response are not known. We hypothesize that shear stress-dependent activation of vascular endothelial growth factor receptor 2 (VEGFR2) causes p38 and ERK1/2 phosphorylation, which contribute to shear stress-induced angiogenesis. Skeletal muscle microvascular endothelial cells were sheared (12 dynes/cm(2), 0.5-24 h). VEGFR2-Y1214 phosphorylation increased in response to elevated shear stress and VEGF stimulation. p38 and ERK1/2 phosphorylation increased at 2 h of shear stress but only p38 remained phosphorylated at 6 and 24 h of shear stress. VEGFR2 inhibition abrogated p38, but not ERK1/2 phosphorylation. VEGF production was increased in response to shear stress at 6 h, and this increased production was abolished by p38 inhibition. Male Sprague-Dawley rats were administered prazosin (50 mg/L drinking water, 1, 2, 4, or 7 days) to induce chronically elevated capillary shear stress in skeletal muscle. In some experiments, mini-osmotic pumps were used to dispense p38 inhibitor SB203580 or its inactive analog SB202474, to the extensor digitorum longus (EDL) of control and prazosin-treated rats. Immunostaining and Western blotting showed increases in p38 phosphorylation in capillaries from rats treated with prazosin for 2 days but returned to basal levels at 4 and 7 days. p38 inhibition abolished the increase in capillary to muscle fiber ratio seen after 7 days of prazosin treatment. Our data suggest that p38 activation is necessary for shear stress-dependent angiogenesis.

  13. Influence of mesenchymal stem cells on the response of endothelial cells to laminar flow and shear stress.

    PubMed

    Hong, Minsung; Jo, Hansu; Ankeny, Randell F; Holliday-Ankeny, Casey J; Kim, Hyengseok; Khang, Gilson; Nerem, Robert M

    2013-01-01

    The interactions between endothelial cells (ECs) and smooth muscle cells (SMCs) in a complex hemodynamic environment play an important role in the control of blood vessel function. Since autologous SMCs are not readily available for the tissue engineering of a blood vessel substitute, a substitute for SMCs, such as human adult bone marrow-derived mesenchymal stem cells (MSCs), is needed. The objective of this study was to use a three-dimensional coculture model of the blood vessel wall, comprised of ECs and MSCs, to determine how the presence of MSCs affects EC function. Two vascular coculture models with an EC monolayer were created using type I collagen. All models were exposed to steady laminar flow with a shear stress of 15 dyn/cm(2) for up to 48 h. ECs in both the MSC and SMC coculture models expressed up-regulated EC-specific markers compared to the EC-only control model. The most dramatic difference observed between the two coculture models was in the experiments assessing monocyte adhesion. Here, fewer monocytes bound after laminar shear compared to static conditions; however, the number of bound monocytes was much lower for the EC-MSC coculture model than the EC-SMC coculture model for both static and shear conditions. These results suggest the feasibility of developing a tissue-engineered blood vessel substitute using MSCs as a substitute for SMCs.

  14. MicroRNA Mediation of Endothelial Inflammatory Response to Smooth Muscle Cells and its Inhibition by Atheroprotective Shear Stress

    PubMed Central

    Chen, Li-Jing; Chuang, Li; Huang, Yi-Hsuan; Zhou, Jing; Lim, Seh Hong; Lee, Chih-I; Lin, Wei-Wen; Lin, Ting-Er; Wang, Wei-Li; Chen, Linyi; Chien, Shu; Chiu, Jeng-Jiann

    2015-01-01

    Rationale In atherosclerotic lesions, synthetic smooth muscle cells (sSMCs) induce aberrant microRNA (miR) profiles in endothelial cells (ECs) under flow stagnation. Increase in shear stress induces favorable miR modulation to mitigate sSMC-induced inflammation. Objective To address the role of miRs in sSMC-induced EC inflammation and its inhibition by shear stress. Methods and Results Co-culturing ECs with sSMCs under static condition causes initial increases of four anti-inflammatory miRs (146a/708/451/98) in ECs followed by decreases below basal levels at 7 days; the increases for miR-146a/708 peaked at 24 h and those for miR-451/98 lasted for only 6-12 h. Shear stress (12 dynes/cm2) to co-cultured ECs for 24 h augments these four miR expressions. In vivo, these four miRs are highly expressed in neointimal ECs in injured arteries under physiological levels of flow, but not expressed under flow stagnation. MiR-146a, -708, -451, and -98 target interleukin (IL)-1 receptor-associated kinase, inhibitor of nuclear factor-κB (NF-κB) kinase subunit-γ, IL-6 receptor, and conserved helix-loop-helix ubiquitous kinase, respectively, to inhibit NF-κB signaling, which exerts negative feedback control on the biogenesis of these miRs. NF-E2-related factor-2 (Nrf-2) is critical for shear-induction of miR-146a in co-cultured ECs. Silencing either Nrf-2 or miR-146a led to increased neointima formation of injured rat carotid artery under physiological levels of flow. Overexpressing miR-146a inhibits neointima formation of rat or mouse carotid artery induced by injury or flow cessation. Conclusions Nrf-2-mediated miR-146a expression is augmented by atheroprotective shear stress in ECs adjacent to sSMCs to inhibit neointima formation of injured arteries. PMID:25623956

  15. Parallel-plate Flow Chamber and Continuous Flow Circuit to Evaluate Endothelial Progenitor Cells under Laminar Flow Shear Stress

    PubMed Central

    Lane, Whitney O.; Jantzen, Alexandra E.; Carlon, Tim A.; Jamiolkowski, Ryan M.; Grenet, Justin E.; Ley, Melissa M.; Haseltine, Justin M.; Galinat, Lauren J.; Lin, Fu-Hsiung; Allen, Jason D.; Truskey, George A.; Achneck, Hardean E.

    2012-01-01

    The overall goal of this method is to describe a technique to subject adherent cells to laminar flow conditions and evaluate their response to well quantifiable fluid shear stresses1. Our flow chamber design and flow circuit (Fig. 1) contains a transparent viewing region that enables testing of cell adhesion and imaging of cell morphology immediately before flow (Fig. 11A, B), at various time points during flow (Fig. 11C), and after flow (Fig. 11D). These experiments are illustrated with human umbilical cord blood-derived endothelial progenitor cells (EPCs) and porcine EPCs2,3. This method is also applicable to other adherent cell types, e.g. smooth muscle cells (SMCs) or fibroblasts. The chamber and all parts of the circuit are easily sterilized with steam autoclaving. In contrast to other chambers, e.g. microfluidic chambers, large numbers of cells (> 1 million depending on cell size) can be recovered after the flow experiment under sterile conditions for cell culture or other experiments, e.g. DNA or RNA extraction, or immunohistochemistry (Fig. 11E), or scanning electron microscopy5. The shear stress can be adjusted by varying the flow rate of the perfusate, the fluid viscosity, or the channel height and width. The latter can reduce fluid volume or cell needs while ensuring that one-dimensional flow is maintained. It is not necessary to measure chamber height between experiments, since the chamber height does not depend on the use of gaskets, which greatly increases the ease of multiple experiments. Furthermore, the circuit design easily enables the collection of perfusate samples for analysis and/or quantification of metabolites secreted by cells under fluid shear stress exposure, e.g. nitric oxide (Fig. 12)6. PMID:22297325

  16. Parallel-plate flow chamber and continuous flow circuit to evaluate endothelial progenitor cells under laminar flow shear stress.

    PubMed

    Lane, Whitney O; Jantzen, Alexandra E; Carlon, Tim A; Jamiolkowski, Ryan M; Grenet, Justin E; Ley, Melissa M; Haseltine, Justin M; Galinat, Lauren J; Lin, Fu-Hsiung; Allen, Jason D; Truskey, George A; Achneck, Hardean E

    2012-01-17

    The overall goal of this method is to describe a technique to subject adherent cells to laminar flow conditions and evaluate their response to well quantifiable fluid shear stresses. Our flow chamber design and flow circuit (Fig. 1) contains a transparent viewing region that enables testing of cell adhesion and imaging of cell morphology immediately before flow (Fig. 11A, B), at various time points during flow (Fig. 11C), and after flow (Fig. 11D). These experiments are illustrated with human umbilical cord blood-derived endothelial progenitor cells (EPCs) and porcine EPCs. This method is also applicable to other adherent cell types, e.g. smooth muscle cells (SMCs) or fibroblasts. The chamber and all parts of the circuit are easily sterilized with steam autoclaving. In contrast to other chambers, e.g. microfluidic chambers, large numbers of cells (> 1 million depending on cell size) can be recovered after the flow experiment under sterile conditions for cell culture or other experiments, e.g. DNA or RNA extraction, or immunohistochemistry (Fig. 11E), or scanning electron microscopy. The shear stress can be adjusted by varying the flow rate of the perfusate, the fluid viscosity, or the channel height and width. The latter can reduce fluid volume or cell needs while ensuring that one-dimensional flow is maintained. It is not necessary to measure chamber height between experiments, since the chamber height does not depend on the use of gaskets, which greatly increases the ease of multiple experiments. Furthermore, the circuit design easily enables the collection of perfusate samples for analysis and/or quantification of metabolites secreted by cells under fluid shear stress exposure, e.g. nitric oxide (Fig. 12).

  17. Impact of main branch stenting on endothelial shear stress: role of side branch diameter, angle and lesion.

    PubMed

    Chen, Henry Y; Moussa, Issam D; Davidson, Charles; Kassab, Ghassan S

    2012-06-07

    In-stent restenosis and stent thrombosis remain clinically significant problems for bifurcation lesions. The objective of this study is to determine the haemodynamic effect of the side branch (SB) on main branch (MB) stenting. We hypothesize that the presence of a SB has a negative effect on MB wall shear stress (WSS), wall shear stress gradient (WSSG) and oscillatory shear index (OSI); and that the bifurcation diameter ratio (SB diameter/MB diameter) and angle are important contributors. We further hypothesized that stent undersizing exaggerates the negative effects on WSS, WSSG and OSI. To test these hypotheses, we developed computational models of stents and non-Newtonian blood. The models were then interfaced, meshed and solved in a validated finite-element package. Stents at bifurcation models were created with 30° and 70° bifurcation angles and bifurcations with diameter ratios of SB/MB = 1/2 and 3/4. It was found that stents placed in the MB at a bifurcation lowered WSS dramatically, while elevating WSSG and OSI. Undersizing the stent exaggerated the decrease in WSS, increase in WSSG and OSI, and disturbed the flow between the struts and the vessel wall. Stenting the MB at bifurcations with larger SB/MB ratios or smaller SB angles (30°) resulted in lower WSS, higher WSSG and OSI. Stenosis at the SB lowered WSS and elevated WSSG and OSI. These findings highlight the effects of major biomechanical factors in MB stenting on endothelial WSS, WSSG, OSI and suggests potential mechanisms for the potentially higher adverse clinical events associated with bifurcation stenting.

  18. Neutrophil adhesion on endothelial cells in a novel asymmetric stenosis model: effect of wall shear stress gradients.

    PubMed

    Rouleau, Leonie; Copland, Ian B; Tardif, Jean-Claude; Mongrain, Rosaire; Leask, Richard L

    2010-09-01

    Leukocytes play a pivotal role in the progression of atherosclerosis. A novel three-dimensional in vitro asymmetric stenosis model was used to better investigate the role of local hemodynamics in the adhesion of leukocytes to an established plaque. The adhesion of a human promyelocytic cell line (NB4) on a human abdominal aortic endothelial cell (EC) monolayer was quantified. NB4 cells were circulated over TNF-alpha stimulated and nonstimulated ECs for 1 or 6 h at 1.25 or 6.25 dynes/cm(2) and compared to static conditions. Cytokine stimulation increased significantly EC expression of intercellular adhesion molecule and vascular cell adhesion molecule. Under static conditions, neutrophils adhered overall more than under flow, with decreased adhesion with increasing shear. Adhesion was significantly higher in the recirculation region distal to the stenosis than in the inlet. Preshearing the ECs decreased the expression of cell adhesion molecules in inflamed endothelium and significantly decreased adhesion. However, the ratio of adhesion between the recirculation zone and the inlet increased, hence exhibiting an increased regional difference. This work suggests an important role for neutrophil-EC interactions in the atherosclerotic process, especially in wall shear stress gradient regions. This is important clinically, potentially helping to explain plaque stability.

  19. PAF mediates neutrophil adhesion to thrombin or TNF-stimulated endothelial cells under shear stress.

    PubMed

    Macconi, D; Foppolo, M; Paris, S; Noris, M; Aiello, S; Remuzzi, G; Remuzzi, A

    1995-07-01

    Platelet-activating factor (PAF) is known to modulate polymorphonuclear leukocyte (PMN) adhesion to endothelial cells cultured under static conditions and activated by thrombin. In contrast, there are no data on the role of PAF in PMN adhesion to cells exposed to flow conditions and activated by stimuli other than thrombin. Here we used the PAF receptor antagonist L-659,989 to evaluate PMN adhesion to human umbilical vein endothelial cells (HUVEC) in basal conditions or upon challenge with thrombin or tumor necrosis factor-alpha (TNF-alpha). Experiments were performed under dynamic flow using a parallel-plate flow chamber and a computer-based image analysis system. Rolling and adhesion of PMNs to endothelial cells significantly increased upon stimulation with thrombin. Thrombin-stimulated HUVEC also synthesized higher amounts of PAF than untreated cells. Pretreatment of PMNs with L-659,989 significantly reduced their rolling and adhesion to thrombin-activated HUVEC. Stimulation of HUVEC with TNF-alpha significantly increased the number of rolling and adherent PMNs as compared with untreated cells. Adhesion of PMNs to and migration across TNF-alpha-stimulated HUVEC were reduced by L-659,989, whereas cell rolling was unchanged. We conclude that PAF mediates leukocyte interaction under flow conditions with HUVEC activated by inflammatory stimuli.

  20. MicroRNA-101 mediates the suppressive effect of laminar shear stress on mTOR expression in vascular endothelial cells

    SciTech Connect

    Chen, Kui; Fan, Wendong; Wang, Xing; Ke, Xiao; Wu, Guifu; Hu, Chengheng

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer Laminar shear stress upregulates miR-101 expression in vascular endothelial cells. Black-Right-Pointing-Pointer miR-101 represses mTOR expression through a specific 3 Prime UTR binding site. Black-Right-Pointing-Pointer Overexpression of miR-101 inhibits G1/S transition and endothelial cell proliferation. Black-Right-Pointing-Pointer Blockade of miR-101 attenuates the suppressive effect of laminar flow on mTOR expression. -- Abstract: Shear stress associated with blood flow plays an important role in regulating gene expression and cell function in endothelial cells (ECs). MicroRNAs (miRNAs) are highly conserved, small non-coding RNAs that negatively regulate the expression of target genes by binding to the mRNA 3 Prime -untranslated region (3 Prime UTR) at the posttranscriptional level involved in diverse cellular processes. This study demonstrates that microRNA-101 in response to laminar shear stress (LSS) is involved in the flow regulation of gene expression in ECs. qRT-PCR analysis showed that miR-101 expression was significantly upregulated in human umbilical vein endothelial cells (HUVECs) exposed to 12 dyn/cm{sup 2} laminar shear stress for 12 h. We found that transfection of miR-101 significantly decreased the luciferase activity of plasmid reporter containing the 3 Prime UTR of mammalian target of rapamycin (mTOR) gene. Western analysis revealed that the protein level of mTOR was significantly reduced in ECs transfected with miR-101. Furthermore, miR-101 overexpression induced cell cycle arrest at the G1/S transition and suppressed endothelial cell proliferation. Finally, transfection of miR-101 inhibitors attenuated the suppressive effects of LSS on mTOR expression, which identified the efficacy of loss-of-function of miR-101 in laminar flow-treated ECs. In conclusion, we have demonstrated that upregulation of miR-101 in response to LSS contributes to the suppressive effects of LSS on mTOR expression and EC

  1. Nuclear envelope proteins Nesprin2 and LaminA regulate proliferation and apoptosis of vascular endothelial cells in response to shear stress.

    PubMed

    Han, Yue; Wang, Lu; Yao, Qing-Ping; Zhang, Ping; Liu, Bo; Wang, Guo-Liang; Shen, Bao-Rong; Cheng, Binbin; Wang, Yingxiao; Jiang, Zong-Lai; Qi, Ying-Xin

    2015-05-01

    The dysfunction of vascular endothelial cells (ECs) influenced by flow shear stress is crucial for vascular remodeling. However, the roles of nuclear envelope (NE) proteins in shear stress-induced EC dysfunction are still unknown. Our results indicated that, compared with normal shear stress (NSS), low shear stress (LowSS) suppressed the expression of two types of NE proteins, Nesprin2 and LaminA, and increased the proliferation and apoptosis of ECs. Targeted small interfering RNA (siRNA) and gene overexpression plasmid transfection revealed that Nesprin2 and LaminA participate in the regulation of EC proliferation and apoptosis. A protein/DNA array was further used to detect the activation of transcription factors in ECs following transfection with target siRNAs and overexpression plasmids. The regulation of AP-2 and TFIID mediated by Nesprin2 and the activation of Stat-1, Stat-3, Stat-5 and Stat-6 by LaminA were verified under shear stress. Furthermore, using Ingenuity Pathway Analysis software and real-time RT-PCR, the effects of Nesprin2 or LaminA on the downstream target genes of AP-2, TFIID, and Stat-1, Stat-3, Stat-5 and Stat-6, respectively, were investigated under LowSS. Our study has revealed that NE proteins are novel mechano-sensitive molecules in ECs. LowSS suppresses the expression of Nesprin2 and LaminA, which may subsequently modulate the activation of important transcription factors and eventually lead to EC dysfunction.

  2. A model for shear stress sensing and transmission in vascular endothelial cells.

    PubMed

    Mazzag, Bori M; Tamaresis, John S; Barakat, Abdul I

    2003-06-01

    Arterial endothelial cell (EC) responsiveness to flow is essential for normal vascular function and plays a role in the development of atherosclerosis. EC flow responses may involve sensing of the mechanical stimulus at the cell surface with subsequent transmission via cytoskeleton to intracellular transduction sites. We had previously modeled flow-induced deformation of EC-surface flow sensors represented as viscoelastic materials with standard linear solid behavior (Kelvin bodies). In the present article, we extend the analysis to arbitrary networks of viscoelastic structures connected in series and/or parallel. Application of the model to a system of two Kelvin bodies in parallel reveals that flow induces an instantaneous deformation followed by creeping to the asymptotic response. The force divides equally between the two bodies when they have identical viscoelastic properties. When one body is stiffer than the other, a larger fraction of the applied force is directed to the stiffer body. We have also probed the impact of steady and oscillatory flow on simple sensor-cytoskeleton-nucleus networks. The results demonstrated that, consistent with the experimentally observed temporal chronology of EC flow responses, the flow sensor attains its peak deformation faster than intracellular structures and the nucleus deforms more rapidly than cytoskeletal elements. The results have also revealed that a 1-Hz oscillatory flow induces significantly smaller deformations than steady flow. These results may provide insight into the mechanisms behind the experimental observations that a number of EC responses induced by steady flow are not induced by oscillatory flow.

  3. Shear stress and 17beta-estradiol modulate cerebral microvascular endothelial Na-K-Cl cotransporter and Na/H exchanger protein levels.

    PubMed

    Chang, Elaine; O'Donnell, Martha E; Barakat, Abdul I

    2008-01-01

    Ion transporters of blood-brain barrier (BBB) endothelial cells play an important role in regulating the movement of ions between the blood and brain. During ischemic stroke, reduction in cerebral blood flow is accompanied by transport of Na and Cl from the blood into the brain, with consequent brain edema formation. We have shown previously that a BBB Na-K-Cl cotransporter (NKCC) participates in ischemia-induced brain Na and water uptake and that a BBB Na/H exchanger (NHE) may also participate. While the abrupt reduction of blood flow is a prominent component of ischemia, the effects of flow on BBB NKCC and NHE are not known. In the present study, we examined the effects of changes in shear stress on NKCC and NHE protein levels in cerebral microvascular endothelial cells (CMECs). We have shown previously that estradiol attenuates both ischemia-induced cerebral edema and CMEC NKCC activity. Thus, in the present study, we also examined the effects of estradiol on NKCC and NHE protein levels in CMECs. Exposing CMECs to steady shear stress (19 dyn/cm(2)) increased the abundance of both NKCC and NHE. Estradiol abolished the shear stress-induced increase in NHE but not NKCC. Abrupt reduction of shear stress did not alter NKCC or NHE abundance in the absence of estradiol, but it decreased NKCC abundance in estradiol-treated cells. Our results indicate that changes in shear stress modulate BBB NKCC and NHE protein levels. They also support the hypothesis that estradiol attenuates edema formation in ischemic stroke in part by reducing the abundance of BBB NKCC protein.

  4. Expression of cathepsin K is regulated by shear stress in cultured endothelial cells and is increased in endothelium in human atherosclerosis.

    PubMed

    Platt, Manu O; Ankeny, Randall F; Shi, Guo-Ping; Weiss, Daiana; Vega, J D; Taylor, W R; Jo, Hanjoong

    2007-03-01

    Cathepsins, the lysosomal cysteine proteases, are involved in vascular remodeling and atherosclerosis. Genetic knockout of cathepsins S and K in mice has shown to reduce atherosclerosis, although the molecular mechanisms remain unclear. Because atherosclerosis preferentially occurs in arteries exposed to disturbed flow conditions, we hypothesized that shear stress would regulate cathepsin K expression and activity in endothelial cells. Mouse aortic endothelial cells (MAEC) exposed to proatherogenic oscillatory shear (OS, +/- 5 dyn/cm(2) for 1 day) showed significantly higher cathepsin K expression and activity than that of atheroprotective, unidirectional laminar shear stress (LS, 15 dyn/cm(2) for 1 day). Western blot and active-site labeling studies showed an active, mature form of cathepsin K in the conditioned medium of MAEC exposed to OS but not in that of LS. Functionally, MAEC exposed to OS significantly increased elastase and gelatinase activity above that of LS. The OS-dependent elastase and gelatinase activities were significantly reduced by knocking down cathepsin K with small-interfering (si) RNA, but not by a nonsilencing siRNA control, suggesting that cathepsin K is a shear-sensitive protease. In addition, immunohistochemical analysis of atherosclerotic human coronary arteries showed a positive correlation between the cathepsin K expression levels in endothelium and elastic lamina integrity. These findings suggest that cathepsin K is a mechanosensitive, extracellular matrix protease that, in turn, may be involved in arterial wall remodeling and atherosclerosis.

  5. Shear stress stimulates phosphorylation of endothelial nitric-oxide synthase at Ser1179 by Akt-independent mechanisms: role of protein kinase A

    NASA Technical Reports Server (NTRS)

    Boo, Yong Chool; Sorescu, George; Boyd, Nolan; Shiojima, Ichiro; Walsh, Kenneth; Du, Jie; Jo, Hanjoong

    2002-01-01

    Recently, we have shown that shear stress stimulates NO(*) production by the protein kinase B/Akt (Akt)-dependent mechanisms in bovine aortic endothelial cells (BAEC) (Go, Y. M., Boo, Y. C., Park, H., Maland, M. C., Patel, R., Pritchard, K. A., Jr., Fujio, Y., Walsh, K., Darley-Usmar, V., and Jo, H. (2001) J. Appl. Physiol. 91, 1574-1581). Akt has been believed to regulate shear-dependent production of NO(*) by directly phosphorylating endothelial nitric-oxide synthase (eNOS) at the Ser(1179) residue (eNOS-S(1179)), but a critical evaluation using specific inhibitors or dominant negative mutants (Akt(AA) or Akt(AAA)) has not been reported. In addition, other kinases, including protein kinase A (PKA) and AMP kinase have also shown to phosphorylate eNOS-S(1179). Here, we show that shear-dependent phosphorylation of eNOS-S(1179) is mediated by an Akt-independent, but a PKA-dependent, mechanism. Expression of Akt(AA) or Akt(AAA) in BAEC by using recombinant adenoviral constructs inhibited phosphorylation of eNOS-S(1179) if cells were stimulated by vascular endothelial growth factor (VEGF), but not by shear stress. As shown before, expression of Akt(AA) inhibited shear-dependent NO(*) production, suggesting that Akt is still an important regulator in NO production. Further studies showed that a selective inhibitor of PKA, H89, inhibited shear-dependent phosphorylation of eNOS-S(1179) and NO(*) production. In contrast, H89 did not inhibit phosphorylation of eNOS-S(1179) induced by expressing a constitutively active Akt mutant (Akt(Myr)) in BAEC, showing that the inhibitor did not affect the Akt pathway. 8-Bromo-cAMP alone phosphorylated eNOS-S(1179) within 5 min without activating Akt, in an H89-sensitive manner. Collectively, these results demonstrate that shear stimulates phosphorylation of eNOS-S(1179) in a PKA-dependent, but Aktindependent manner, whereas the NO(*) production is regulated by the mechanisms dependent on both PKA and Akt. A coordinated interaction

  6. Traction Forces of Endothelial Cells under Slow Shear Flow

    PubMed Central

    Perrault, Cecile M.; Brugues, Agusti; Bazellieres, Elsa; Ricco, Pierre; Lacroix, Damien; Trepat, Xavier

    2015-01-01

    Endothelial cells are constantly exposed to fluid shear stresses that regulate vascular morphogenesis, homeostasis, and disease. The mechanical responses of endothelial cells to relatively high shear flow such as that characteristic of arterial circulation has been extensively studied. Much less is known about the responses of endothelial cells to slow shear flow such as that characteristic of venous circulation, early angiogenesis, atherosclerosis, intracranial aneurysm, or interstitial flow. Here we used a novel, to our knowledge, microfluidic technique to measure traction forces exerted by confluent vascular endothelial cell monolayers under slow shear flow. We found that cells respond to flow with rapid and pronounced increases in traction forces and cell-cell stresses. These responses are reversible in time and do not involve reorientation of the cell body. Traction maps reveal that local cell responses to slow shear flow are highly heterogeneous in magnitude and sign. Our findings unveil a low-flow regime in which endothelial cell mechanics is acutely responsive to shear stress. PMID:26488643

  7. Nitric oxide generation by endothelial cells exposed to shear stress in glass tubes perfused with red blood cell suspensions: role of aggregation.

    PubMed

    Yalcin, Ozlem; Ulker, Pinar; Yavuzer, Ugur; Meiselman, Herbert J; Baskurt, Oguz K

    2008-05-01

    Endothelial function is modulated by wall shear stress acting on the vessel wall, which is determined by fluid velocity and the local viscosity near the vessel wall. Red blood cell (RBC) aggregation may affect the local viscosity by favoring axial migration. The aim of this study was to investigate the role of RBC aggregation, with or without altered plasma viscosity, in the mechanically induced nitric oxide (NO)-related mechanisms of endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultured on the inner surface of cylindrical glass capillaries that were perfused with RBC suspensions having normal and increased aggregation at a nominal shear stress of 15 dyn/cm(2). RBC aggregation was enhanced by two different approaches: 1) poloxamer-coated RBC suspended in normal, autologous plasma, resulting in enhanced aggregation but unchanged plasma viscosity and 2) normal RBC suspended in autologous plasma containing 0.5% dextran (mol mass 500 kDa), with a similar level of RBC aggregation but higher plasma viscosity. Compared with normal cells in unmodified plasma, perfusion with suspensions of poloxamer-coated RBC in normal plasma resulted in decreased levels of NO metabolites and serine 1177 phosphorylation of endothelial nitric oxide synthase (eNOS). Perfusion with normal RBC in plasma containing dextran resulted in a NO level that remained elevated, whereas only a modest decrease of phosphorylated eNOS level was observed. The results of this study suggest that increases of RBC aggregation tendency affect endothelial cell functions by altering local blood composition, especially if the alterations of RBC aggregation are due to modified cellular properties and not to plasma composition changes.

  8. Identification of vascular endothelial genes differentially responsive to fluid mechanical stimuli: cyclooxygenase-2, manganese superoxide dismutase, and endothelial cell nitric oxide synthase are selectively up-regulated by steady laminar shear stress.

    PubMed Central

    Topper, J N; Cai, J; Falb, D; Gimbrone, M A

    1996-01-01

    Early atherosclerotic lesions develop in a topographical pattern that strongly suggests involvement of hemodynamic forces in their pathogenesis. We hypothesized that certain endothelial genes, which exhibit differential responsiveness to distinct fluid mechanical stimuli, may participate in the atherogenic process by modulating, on a local level within the arterial wall, the effects of systemic risk factors. A differential display strategy using cultured human endothelial cells has identified two genes, manganese superoxide dismutase and cyclooxygenase-2, that exhibit selective and sustained up-regulation by steady laminar shear stress (LSS). Turbulent shear stress, a nonlaminar fluid mechanical stimulus, does not induce these genes. The endothelial form of nitric oxide synthase also demonstrates a similar LSS-selective pattern of induction. Thus, three genes with potential atheroprotective (antioxidant, antithrombotic, and antiadhesive) activities manifest a differential response to distinct fluid mechanical stimuli, providing a possible mechanistic link between endothelial gene expression and early events in atherogenesis. The activities of these and other LSS-responsive genes may have important implications for the pathogenesis and prevention of atherosclerosis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8816815

  9. Associated inflammation or increased flow-mediated shear stress, but not pressure alone, disrupts endothelial caveolin-1 in infants with pulmonary hypertension

    PubMed Central

    Dereddy, Narendra; Huang, Jing; Erb, Markus; Guzel, Sibel; Wolk, John H; Sett, Suvro S; Gewitz, Michael H; Mathew, Rajamma

    2012-01-01

    Endothelial caveolin-1 loss is an important feature of pulmonary hypertension (PH); the rescue of caveolin-1 abrogates experimental PH. Recent studies in human PH suggest that the endothelial caveolin-1 loss is followed by an enhanced expression of caveolin-1 in smooth muscle cells (SMC) with subsequent neointima formation. In order to evaluate caveolin-1 expression in infants with PH, we examined the available clinical histories, hemodynamic data, and the expression of caveolin-1, PECAM-1, vWF, and smooth muscle α-actin in the lung biopsy/autopsy specimens obtained from infants with congenital heart disease (CHD, n = 8) and lung disease (n = 9). In CHD group, PH associated with increased pulmonary blood flow exhibited loss of endothelial caveolin-1 and PECAM-1 in pulmonary arteries; additional vWF loss was associated with enhanced expression of caveolin-1 in SMC. In the absence of PH, increased or decreased pulmonary blood flow did not disrupt endothelial caveolin-1, PECAM-1, or vWF; nor was there any enhanced expression of caveolin-1 in SMC. In Lung Disease + PH group, caveolin-1, PECAM-1, and vWF were well preserved in seven infants, and importantly, SMC in these arteries did not exhibit enhanced caveolin-1 expression. Two infants with associated inflammatory disease exhibited loss of endothelial caveolin-1 and PECAM-1; additional loss of vWF was accompanied by enhanced expression of caveolin-1 in SMC. Thus, associated flow-induced shear stress or inflammation, but not elevated pulmonary artery pressure alone, disrupts endothelial caveolin-1. Subsequent vWF loss, indicative of extensive endothelial damage is associated with enhanced expression of caveolin-1 in SMC, which may worsen the disease. PMID:23372934

  10. Aerobic exercise acutely prevents the endothelial dysfunction induced by mental stress among subjects with metabolic syndrome: the role of shear rate.

    PubMed

    Sales, Allan R K; Fernandes, Igor A; Rocha, Natália G; Costa, Lucas S; Rocha, Helena N M; Mattos, João D M; Vianna, Lauro C; Silva, Bruno M; Nóbrega, Antonio C L

    2014-04-01

    Mental stress induces transient endothelial dysfunction, which is an important finding for subjects at cardiometabolic risk. Thus, we tested whether aerobic exercise prevents this dysfunction among subjects with metabolic syndrome (MetS) and whether an increase in shear rate during exercise plays a role in this phenomenon. Subjects with MetS participated in two protocols. In protocol 1 (n = 16), endothelial function was assessed using brachial artery flow-mediated dilation (FMD). Subjects then underwent a mental stress test followed by either 40 min of leg cycling or rest across two randomized sessions. FMD was assessed again at 30 and 60 min after exercise or rest, with a second mental stress test in between. Mental stress reduced FMD at 30 and 60 min after the rest session (baseline: 7.7 ± 0.4%, 30 min: 5.4 ± 0.5%, and 60 min: 3.9 ± 0.5%, P < 0.05 vs. baseline), whereas exercise prevented this reduction (baseline: 7.5 ± 0.4%, 30 min: 7.2 ± 0.7%, and 60 min: 8.7 ± 0.8%, P > 0.05 vs. baseline). Protocol 2 (n = 5) was similar to protocol 1 except that the first period of mental stress was followed by either exercise in which the brachial artery shear rate was attenuated via forearm cuff inflation or exercise without a cuff. Noncuffed exercise prevented the reduction in FMD (baseline: 7.5 ± 0.7%, 30 min: 7.0 ± 0.7%, and 60 min: 8.7 ± 0.8%, P > 0.05 vs. baseline), whereas cuffed exercise failed to prevent this reduction (baseline: 7.5 ± 0.6%, 30 min: 5.4 ± 0.8%, and 60 min: 4.1 ± 0.9%, P < 0.05 vs. baseline). In conclusion, exercise prevented mental stress-induced endothelial dysfunction among subjects with MetS, and an increase in shear rate during exercise mediated this effect.

  11. Determinants of shear stress-stimulated endothelial nitric oxide production assessed in real-time by 4,5-diaminofluorescein fluorescence.

    PubMed

    Qiu, W; Kass, D A; Hu, Q; Ziegelstein, R C

    2001-08-17

    The extremely short biological half-life of endothelial-derived nitric oxide (NO) has impeded real-time measurements of NO synthesis. We used the membrane-permeable fluorescent probe 4,5-diaminofluorescein diacetate (DAF-2 DA) to study determinants of NO synthesis in bovine aortic endothelial cells (BAECs). A step increase in shear stress (SS) from 0.3 to 3.4 dyne/cm(2) triggered an increase in DAF-2 fluorescence starting 3.0 +/- 0.5 min after the flow rise and peaking at 44.7 +/- 7.2 min. This was abolished by intracellular Ca(2+) chelation, but was unaffected by blocking extracellular Ca(2+) influx or by inhibiting SS-related changes in intracellular pH. The increase in DAF-2 fluorescence occurred significantly earlier in BAECs transfected with either superoxide dismutase (SOD) or catalase (CAT), indicating concomitant reactive oxygen species (ROS) generation by SS and "competition" between ROS- and DAF-2-NO interactions. These data provide novel insights into several NO signaling determinants and reveal that DAF-2 can assess real-time SS-stimulated NO synthesis in endothelial cells. This should facilitate the analysis of NO-signaling pathways.

  12. Shear stress regulates HUVEC hydraulic conductivity by occludin phosphorylation.

    PubMed

    Pang, Zhengyu; Antonetti, David A; Tarbell, John M

    2005-11-01

    Human umbilical vein endothelial cells (HUVECs) display hydraulic conductivity (L(P)) responses to shear stress that differ markedly from the responses of bovine aortic endothelial cells (BAECs). In HUVECs, 5, 10, and 20 dyn cm(-2) steady shear stress transiently increased L(P) with a return to preshear baseline after a 2-h exposure to shear stress. Pure oscillatory shear stress of 0 +/- 20 dyn cm(-2) (mean+/-amplitude) had no effect on L(P), whereas superposition of oscillatory shear stress on steady shear stress suppressed the effect induced by steady shear stress alone. Shear reversal (amplitude greater than mean) was not necessary for the inhibitory influence of oscillatory shear stress. The transient increase of L(P) by steady shear stress was not affected by incubation with BAPTA-AM (10 microM), suggesting calcium independence of the shear response. Decreasing nitric oxide (NO) concentration with L-NMMA (100 microM), a nitric oxide synthase (NOS) inhibitor, did not inhibit the HUVEC L(P) response to shear stress. At the protein level, 10 dyn cm(-2) shear stress did not affect the total content of occludin, but it did elevate the phosphorylation level transiently. The positive correlation between occludin phosphorylation and hydraulic conductivity parallels observations in BAECs and suggests that occludin phosphorylation may be a general mediator of shear-L(P) responses in diverse endothelial cell types.

  13. Wall shear stress in collapsed tubes

    NASA Astrophysics Data System (ADS)

    Naili, S.; Ribreau, C.

    1999-01-01

    A small flexural wall rigidity brings unique features to cross-sectional shapes and blood flow within veins, which are characterised by a non-uniform hemodynamical environment acting upon endothelial cells. Velocity fields and related wall shear stress were numerically determined for a large number of conditions, assuming a fully developed, steady, incompressible laminar flow through an uniform smooth pipe with a constant cross-section. It was shown that the flatness greatly influences the resulting distribution of the wall shear stresses along the lumen perimeter. For instance, under a steady longitudinal pressure gradient at about 500 Pascal per meter inside a constant oval-shaped tube, with a lumen perimeter of the order of 5 × 10^{-2} meter, the maximum wall shear stress is found at about 2 Pascal where the local curvature is minimal. On the other hand, the minimal wall shear stress of the order of 1 Pascal is found where the local curvature is maximal. Clear indications have been reported showing that the hemodynamical wall shear stress does alter endothelial cell morphology and orientation. These results are being used for developing an experimental set-up in order to locally map out the characteristic shear stresses looking for endothelial shape modifications whenever a viscous fluid flow is applied.

  14. Quantitative characterization of endothelial cell morphologies depending on shear stress in different blood vessels of domestic pigs using a focused ion beam and high resolution scanning electron microscopy (FIB-SEM).

    PubMed

    Pham, Tam Thanh; Maenz, Stefan; Lüdecke, Claudia; Schmerbauch, Christoph; Settmacher, Utz; Jandt, Klaus D; Bossert, Jörg; Zanow, Jürgen

    2015-04-01

    Microstructured surfaces mimicking the endothelial cell (EC) morphology is a new approach to improve the blood compatibility of synthetic vascular grafts. The ECs are capable of changing their shapes depending on different shear conditions. However, the quantitative correlation between EC morphology and shear stress has not yet been investigated statistically. The aim of this study was to quantitatively investigate the morphology of ECs in dependence on the shear stress. Blood flow rates in different types of natural blood vessels (carotid, renal, hepatic and iliac arteries) originated from domestic pigs were first measured in vivo to calculate the shear stresses. The EC morphologies were quantitatively characterized ex vivo by imaging with high resolution scanning electron microscopy (SEM) and cross-sectioning of the cells using a state-of-the-art focused ion beam (FIB). The relationships between EC geometrical parameters and shear stress were statistically analyzed and found to be exponential. ECs under high shear stress conditions had a longer length and narrower width, i.e. a higher aspect ratio, while the cell height was smaller compared to low shear conditions. Based on these results, suitable and valid geometrical parameters of microstructures mimicking EC can be derived for various shear conditions in synthetic vascular grafts to optimize blood compatibility.

  15. Fluid shear stress threshold regulates angiogenic sprouting.

    PubMed

    Galie, Peter A; Nguyen, Duc-Huy T; Choi, Colin K; Cohen, Daniel M; Janmey, Paul A; Chen, Christopher S

    2014-06-03

    The density and architecture of capillary beds that form within a tissue depend on many factors, including local metabolic demand and blood flow. Here, using microfluidic control of local fluid mechanics, we show the existence of a previously unappreciated flow-induced shear stress threshold that triggers angiogenic sprouting. Both intraluminal shear stress over the endothelium and transmural flow through the endothelium above 10 dyn/cm(2) triggered endothelial cells to sprout and invade into the underlying matrix, and this threshold is not impacted by the maturation of cell-cell junctions or pressure gradient across the monolayer. Antagonizing VE-cadherin widened cell-cell junctions and reduced the applied shear stress for a given transmural flow rate, but did not affect the shear threshold for sprouting. Furthermore, both transmural and luminal flow induced expression of matrix metalloproteinase 1, and this up-regulation was required for the flow-induced sprouting. Once sprouting was initiated, continuous flow was needed to both sustain sprouting and prevent retraction. To explore the potential ramifications of a shear threshold on the spatial patterning of new sprouts, we used finite-element modeling to predict fluid shear in a variety of geometric settings and then experimentally demonstrated that transmural flow guided preferential sprouting toward paths of draining interstitial fluid flow as might occur to connect capillary beds to venules or lymphatics. In addition, we show that luminal shear increases in local narrowings of vessels to trigger sprouting, perhaps ultimately to normalize shear stress across the vasculature. Together, these studies highlight the role of shear stress in controlling angiogenic sprouting and offer a potential homeostatic mechanism for regulating vascular density.

  16. Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology

    PubMed Central

    Davies, Peter F

    2010-01-01

    SUMMARY Endothelium lining the cardiovascular system is highly sensitive to hemodynamic shear stresses that act at the vessel luminal surface in the direction of blood flow. Physiological variations of shear stress regulate acute changes in vascular diameter and when sustained induce slow, adaptive, structural-wall remodeling. Both processes are endothelium-dependent and are systemically and regionally compromised by hyperlipidemia, hypertension, diabetes and inflammatory disorders. Shear stress spans a range of spatiotemporal scales and contributes to regional and focal heterogeneity of endothelial gene expression, which is important in vascular pathology. Regions of flow disturbances near arterial branches, bifurcations and curvatures result in complex spatiotemporal shear stresses and their characteristics can predict atherosclerosis susceptibility. Changes in local artery geometry during atherogenesis further modify shear stress characteristics at the endothelium. Intravascular devices can also influence flow-mediated endothelial responses. Endothelial flow-induced responses include a cell-signaling repertoire, collectively known as mechanotransduction, that ranges from instantaneous ion fluxes and biochemical pathways to gene and protein expression. A spatially decentralized mechanism of endothelial mechanotransduction is dominant, in which deformation at the cell surface induced by shear stress is transmitted as cytoskeletal tension changes to sites that are mechanically coupled to the cytoskeleton. A single shear stress mechanotransducer is unlikely to exist; rather, mechanotransduction occurs at multiple subcellular locations. PMID:19029993

  17. A Piezoelectric Shear Stress Sensor

    NASA Technical Reports Server (NTRS)

    Kim, Taeyang; Saini, Aditya; Kim, Jinwook; Gopalarathnam, Ashok; Zhu, Yong; Palmieri, Frank L.; Wohl, Christopher J.; Jiang, Xiaoning

    2016-01-01

    In this paper, a piezoelectric sensor with a floating element was developed for shear stress measurement. The piezoelectric sensor was designed to detect the pure shear stress suppressing effects of normal stress generated from the vortex lift-up by applying opposite poling vectors to the: piezoelectric elements. The sensor was first calibrated in the lab by applying shear forces and it showed high sensitivity to shear stress (=91.3 +/- 2.1 pC/Pa) due to the high piezoelectric coefficients of PMN-33%PT (d31=-1330 pC/N). The sensor also showed almost no sensitivity to normal stress (less than 1.2 pC/Pa) because of the electromechanical symmetry of the device. The usable frequency range of the sensor is 0-800 Hz. Keywords: Piezoelectric sensor, shear stress, floating element, electromechanical symmetry

  18. Shear stress induced stimulation of mammalian cell metabolism

    NASA Technical Reports Server (NTRS)

    Mcintire, L. V.; Frangos, J. A.; Eskin, S. G.

    1988-01-01

    A flow apparatus was developed for the study of the metabolic response of anchorage dependent cells to a wide range of steady and pulsatile shear stresses under well controlled conditions. Human umbilical vein endothelial cell monolayers were subjected to steady shear stresses of up to 24 dynes/sq cm, and the production of prostacyclin was determined. The onset of flow led to a burst in prostacyclin production which decayed to a long term steady state rate (SSR). The SSR of cells exposed to flow was greater than the basal release level, and increased linearly with increasing shear stress. It is demonstrated that shear stresses in certain ranges may not be detrimental to mammalian cell metabolism. In fact, throughout the range of shear stresses studied, metabolite production is maximized by maximizing shear stress.

  19. Oscillatory shear stress stimulates endothelial production of O2- from p47phox-dependent NAD(P)H oxidases, leading to monocyte adhesion

    NASA Technical Reports Server (NTRS)

    Hwang, Jinah; Saha, Aniket; Boo, Yong Chool; Sorescu, George P.; McNally, J. Scott; Holland, Steven M.; Dikalov, Sergei; Giddens, Don P.; Griendling, Kathy K.; Harrison, David G.; Jo, Hanjoong

    2003-01-01

    Arterial regions exposed to oscillatory shear (OS) in branched arteries are lesion-prone sites of atherosclerosis, whereas those of laminar shear (LS) are relatively well protected. Here, we examined the hypothesis that OS and LS differentially regulate production of O2- from the endothelial NAD(P)H oxidase, which, in turn, is responsible for their opposite effects on a critical atherogenic event, monocyte adhesion. We used aortic endothelial cells obtained from C57BL/6 (MAE-C57) and p47phox-/- (MAE-p47-/-) mice, which lack a component of NAD(P)H oxidase. O2- production was determined by dihydroethidium staining and an electron spin resonance using an electron spin trap methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine. Chronic exposure (18 h) to an arterial level of OS (+/- 5 dynes/cm2) increased O2- (2-fold) and monocyte adhesion (3-fold) in MAE-C57 cells, whereas chronic LS (15 dynes/cm2, 18 h) significantly decreased both monocyte adhesion and O2- compared with static conditions. In contrast, neither LS nor OS were able to induce O2- production and monocyte adhesion to MAE-p47-/-. Treating MAE-C57 with a cell-permeable superoxide dismutase compound, polyethylene glycol-superoxide dismutase, also inhibited OS-induced monocyte adhesion. In addition, over-expressing p47phox in MAE-p47-/- restored OS-induced O2- production and monocyte adhesion. These results suggest that chronic exposure of endothelial cells to OS stimulates O2- and/or its derivatives produced from p47phox-dependent NAD(P)H oxidase, which, in turn, leads to monocyte adhesion, an early and critical atherogenic event.

  20. MEMS shear stress sensors for cardiovascular diagnostics.

    PubMed

    Soundararajan, Gopikrishnan; Hsiai, Tzung K; DeMaio, Lucas; Chang, Michael; Chang, Stanley

    2004-01-01

    Coronary artery disease is the leading cause of morbidity and mortality in the industrialized nations. Both biochemical and biomechanical stimuli modulate the pathogenesis of coronary artery diseases. Shear stress acting on the lumen of blood vessels intimately modulates the biological activities of vascular endothelial cells (ECs). We hereby develop microelectro mechanical system (MEMS)-based sensors at the dimension comparable to a single EC to monitor realtime shear stress in fluidic channel. Our goal is to fabricate sensors for ex vivo or in vivo shear stress measurement at Reynolds number commonly encountered in human circulation. The MEMS sensors were designed based on the previously described heat transfer principles. The polysilicon was doped with phosphorous to render the sensing element a high resistivity at 2.5 KOmega. The development of backside wire bonding enabled the application for the vascular geometry. The small dimension (80x2 mum) and the gain amplitude at 71 KHz offered an entry point to measure shear stress with high spatial and temporal resolution.

  1. Yield shear stress and disaggregating shear stress of human blood

    NASA Astrophysics Data System (ADS)

    Jung, Jinmu; Lee, Byoung-Kwon; Shin, Sehyun

    2014-05-01

    This review presents two distinct rheological parameters of blood that have the potential to indicate blood circulation adequacy: yield shear stress (YSS) and disaggregating shear stress (DSS). YSS and DSS reflect the strength of red blood cell (RBC) aggregation in suspension under static and dynamic conditions, respectively. YSS, defined as the critical stress to disperse RBC aggregates under static conditions, was found to be dependent upon hematocrit, fibrinogen, and red cell deformability, but not temperature. DSS, defined as the minimum shear stress to disperse RBC aggregates under dynamic conditions, is dependent upon fibrinogen, red cell deformability, and temperature but not hematocrit. Owing to recent advances in measurement technology, these two parameters can be easily measured, and thus, their clinical significance in blood circulation can be verified.

  2. Chronic shear induces caveolae formation and alters ERK and Akt responses in endothelial cells

    NASA Technical Reports Server (NTRS)

    Boyd, Nolan L.; Park, Heonyong; Yi, Hong; Boo, Yong Chool; Sorescu, George P.; Sykes, Michelle; Jo, Hanjoong

    2003-01-01

    Caveolae are plasmalemmal domains enriched with cholesterol, caveolins, and signaling molecules. Endothelial cells in vivo are continuously exposed to shear conditions, and their caveolae density and location may be different from that of static cultured cells. Here, we show that chronic shear exposure regulates formation and localization of caveolae and caveolin-1 in bovine aortic endothelial cells (BAEC). Chronic exposure (1 or 3 days) of BAEC to laminar shear increased the total number of caveolae by 45-48% above static control. This increase was due to a rise in the luminal caveolae density without changing abluminal caveolae numbers or increasing caveolin-1 mRNA and protein levels. Whereas some caveolin-1 was found in the plasma membrane in static-cultured cells, it was predominantly localized in the Golgi. In contrast, chronic shear-exposed cells showed intense caveolin-1 staining in the luminal plasma membrane with minimum Golgi association. The preferential luminal localization of caveolae may play an important role in endothelial mechanosensing. Indeed, we found that chronic shear exposure (preconditioning) altered activation patterns of two well-known shear-sensitive signaling molecules (ERK and Akt) in response to a step increase in shear stress. ERK activation was blunted in shear preconditioned cells, whereas the Akt response was accelerated. These results suggest that chronic shear stimulates caveolae formation by translocating caveolin-1 from the Golgi to the luminal plasma membrane and alters cell signaling responses.

  3. [Exercise-induced shear stress: Physiological basis and clinical impact].

    PubMed

    Rodríguez-Núñez, Iván; Romero, Fernando; Saavedra, María Javiera

    2016-01-01

    The physiological regulation of vascular function is essential for cardiovascular health and depends on adequate control of molecular mechanisms triggered by endothelial cells in response to mechanical and chemical stimuli induced by blood flow. Endothelial dysfunction is one of the major risk factors for cardiovascular disease, where an imbalance between synthesis of vasodilator and vasoconstrictor molecules is one of its main mechanisms. In this context, the shear stress is one of the most important mechanical stimuli to improve vascular function, due to endothelial mechanotransduction, triggered by stimulation of various endothelial mechanosensors, induce signaling pathways culminating in increased bioavailability of vasodilators molecules such as nitric oxide, that finally trigger the angiogenic mechanisms. These mechanisms allow providing the physiological basis for the effects of exercise on vascular health. In this review it is discussed the molecular mechanisms involved in the vascular response induced by shear stress and its impact in reversing vascular injury associated with the most prevalent cardiovascular disease in our population.

  4. Adhesion of endothelial cells and endothelial progenitor cells on peptide-linked polymers in shear flow.

    PubMed

    Wang, Xin; Cooper, Stuart

    2013-05-01

    The initial adhesion of human umbilical vein endothelial cells (HUVECs), cord blood endothelial colony-forming cells (ECFCs), and human blood outgrowth endothelial cells (HBOECs) was studied under radial flow conditions. The surface of a variable shear-rate device was either coated with polymer films or covered by synthetic fibers. Spin-coating was applied to produce smooth polymer films, while fibrous scaffolds were generated by electrospinning. The polymer was composed of hexyl methacrylate, methyl methacrylate, poly(ethylene glycol) methacrylate (PEGMA), and CGRGDS peptide. The peptide was incorporated into the polymer system by coupling to an acrylate-PEG-N-hydroxysuccinimide comonomer. A shear-rate-dependent increase of the attached cells with time was observed with all cell types. The adhesion of ECs increased on RGD-linked polymer surfaces compared to polymers without adhesive peptides. The number of attached ECFCs and HBOECs are significantly higher than that of HUVECs within the entire shear-rate range and surfaces examined, especially on RGD-linked polymers at low shear rates. Their superior adhesion ability of endothelial progenitor cells under flow conditions suggests they are a promising source for in vivo seeding of vascular grafts and shows the potential to be used for self-endothelialized implants.

  5. Computer-controlled microcirculatory support system for endothelial cell culture and shearing.

    PubMed

    Song, Jonathan W; Gu, Wei; Futai, Nobuyuki; Warner, Kristy A; Nor, Jacques E; Takayama, Shuichi

    2005-07-01

    Endothelial cells (ECs) lining the inner lumen of blood vessels are continuously subjected to hemodynamic shear stress, which is known to modify EC morphology and biological activity. This paper describes a self-contained microcirculatory EC culture system that efficiently studies such effects of shear stress on EC alignment and elongation in vitro. The culture system is composed of elastomeric microfluidic cell shearing chambers interfaced with computer-controlled movement of piezoelectric pins on a refreshable Braille display. The flow rate is varied by design of channels that allow for movement of different volumes of fluid per variable-speed pump stroke. The integrated microfluidic valving and pumping system allowed primary EC seeding and differential shearing in multiple compartments to be performed on a single chip. The microfluidic flows caused ECs to align and elongate significantly in the direction of flow according to their exposed levels of shear stress. This microfluidic system overcomes the small flow rates and the inefficiencies of previously described microfluidic and macroscopic systems respectively to conveniently perform parallel studies of EC response to shear stress.

  6. Stress analysis of shear/compression test

    SciTech Connect

    Nishijima, S.; Okada, T.; Ueno, S.

    1997-06-01

    Stress analysis has been made on the glass fiber reinforced plastics (GFRP) subjected to the combined shear and compression stresses by means of finite element method. The two types of experimental set up were analyzed, that is parallel and series method where the specimen were compressed by tilted jigs which enable to apply the combined stresses, to the specimen. Modified Tsai-Hill criterion was employed to judge the failure under the combined stresses that is the shear strength under the compressive stress. The different failure envelopes were obtained between the two set ups. In the parallel system the shear strength once increased with compressive stress then decreased. On the contrary in the series system the shear strength decreased monotonicly with compressive stress. The difference is caused by the different stress distribution due to the different constraint conditions. The basic parameters which control the failure under the combined stresses will be discussed.

  7. On-Chip Evaluation of Shear Stress Effect on Cytotoxicity of Mesoporous Silica Nanoparticles

    PubMed Central

    Kim, Donghyuk; Lin, Yu-Shen; Haynes, Christy L.

    2011-01-01

    In this work, nanotoxicity in the bloodstream was modeled and the cytotoxicity of sub-50 nm mesoporous silica nanoparticles to human endothelial cells was investigated under microfluidic flow conditions. Compared to traditional in vitro cytotoxicity assays performed under static conditions, unmodified mesoporous silica nanoparticles show higher and shear stress-dependent toxicity to endothelial cells under flow conditions. Interestingly, even under flow conditions, highly organo-modified mesoporous silica nanoparticles show no significant toxicity to endothelial cells. This paper clearly demonstrates that shear stress is an important factor to be considered in in vitro nanotoxicology assessments and provides a simple device for pursuing this consideration. PMID:22032307

  8. Effects of the changes in the wall shear stresses (WSS) acting on endothelial cells (EC) during the enlargement of Abdominal Aortic Aneurysms (AAA)

    NASA Astrophysics Data System (ADS)

    Salsac, Anne-Virginie

    2005-03-01

    The changes in the spatial and temporal distribution of the WSS and gradients of WSS during the enlargement of AAAs are important to understand the etiology and progression of this vascular disease, since they affect the wall structural integrity, primarily via the changes induced on the shape, functions and metabolism of the endothelial cells. PIV measurements were performed in aneurysm models, while changing systematically their size and geometry. Two regions with distinct patterns of WSS were identified. The region of flow detachment extends over the proximal half and is characterized by oscillatory WSS of very low mean. The region of flow reattachment, located distally, is dominated by large, negative WSS and sustained gradients of WSS that result from the impact of the vortex ring on the wall. Cultured EC were subjected to these two types of stimuli in vitro. The permeability of the endothelium was found to be largely increased in the flow detachment region. Endothelium cell-cell adhesion, proliferation and apoptosis were also affected by the high gradients of WSS.

  9. On Measuring the Third Dimension of Cultured Endothelial Cells in Shear Flow

    NASA Astrophysics Data System (ADS)

    Liu, S. Q.; Yen, Morris; Fung, Y. C.

    1994-09-01

    The stress in the endothelial cells induced by blood flow depends on the waviness of the blood-endothelium interface and the slopes at the junctions of neighboring cells in the direction of flow. The height and slope in the third dimension of the living endothelial cells cannot be measured by ordinary optical and electron microscopy. Here we show that interference microscopy meets the challenge. We measured the geometry of cultured confluent human vascular endothelial cells in a flow, and we found that in a normal section parallel to the flow, the absolute values of the surface slopes at the cell junctions were 0.70 ± 0.02 (SE) and 0.80 ± 0.02 (SE) at the leading and trailing edges of the cells, respectively, in a culture medium of osmolarity 310 mosM with a shear stress of approximately 1 N/m^2. A reversal of the flow direction led to a reversal of the slope pattern. An increase in medium osmolarity above 310 mosM induced an initial decrease in the slopes followed by a return to normal, whereas a decrease in the osmolarity had a reversed effect. These results, in light of our previous theoretical analyses, show that tensile stress exists in the endothelial cell membrane, and that the mechanism of tension accumulation is a reality. The accumulation is not 100% because the membranes are not smooth at the cell junctions.

  10. Experimental and numerical analyses of local mechanical properties measured by atomic force microscopy for sheared endothelial cells.

    PubMed

    Ohashi, T; Ishii, Y; Ishikawa, Y; Matsumoto, T; Sato, M

    2002-01-01

    Local mechanical properties were measured for bovine endothelial cells exposed to shear stress using an atomic force microscopy (AFM), and the AFM indentations were simulated using a finite element method (FEM) to determine the elastic modulus. After exposure to shear stress, the endothelial cells showed marked elongation and orientation in the flow direction, together with significant decrease in the peak cell height. The applied force-indentation depth curve was obtained at seven different locations on the major axis of the cell surface and quantitatively expressed by the quadratic equation. The elastic modulus was determined by comparison of the experimental and numerical results. The modulus using our FEM model significantly became higher from 12.2+/-4.2 to 18.7+/-5.7 kPa with exposure to shear stress. Fluorescent images showed that stress fibers of F-actin bundles were mainly formed in the central portion of the sheared cells. The significant increase in the modulus may be due to this remodeling of cytoskeletal structure. The moduli using the Hertz model are 0.87+/-0.23 and 1.75+/-0.43 kPa for control and sheared endothelial cells respectively. This difference can be attributable to the differences in approximation functions to determine the elastic modulus. The elastic modulus would contribute a better understanding of local mechanical properties of the cells.

  11. Endothelial cell respiration is affected by the oxygen tension during shear exposure: role of mitochondrial peroxynitrite.

    PubMed

    Jones, Charles I; Han, Zhaosheng; Presley, Tennille; Varadharaj, Saradhadevi; Zweier, Jay L; Ilangovan, Govindasamy; Alevriadou, B Rita

    2008-07-01

    Cultured vascular endothelial cell (EC) exposure to steady laminar shear stress results in peroxynitrite (ONOO(-)) formation intramitochondrially and inactivation of the electron transport chain. We examined whether the "hyperoxic state" of 21% O(2), compared with more physiological O(2) tensions (Po(2)), increases the shear-induced nitric oxide (NO) synthesis and mitochondrial superoxide (O(2)(*-)) generation leading to ONOO(-) formation and suppression of respiration. Electron paramagnetic resonance oximetry was used to measure O(2) consumption rates of bovine aortic ECs sheared (10 dyn/cm(2), 30 min) at 5%, 10%, or 21% O(2) or left static at 5% or 21% O(2). Respiration was inhibited to a greater extent when ECs were sheared at 21% O(2) than at lower Po(2) or left static at different Po(2). Flow in the presence of an endothelial NO synthase (eNOS) inhibitor or a ONOO(-) scavenger abolished the inhibitory effect. EC transfection with an adenovirus that expresses manganese superoxide dismutase in mitochondria, and not a control virus, blocked the inhibitory effect. Intracellular and mitochondrial O(2)(*-) production was higher in ECs sheared at 21% than at 5% O(2), as determined by dihydroethidium and MitoSOX red fluorescence, respectively, and the latter was, at least in part, NO-dependent. Accumulation of NO metabolites in media of ECs sheared at 21% O(2) was modestly increased compared with ECs sheared at lower Po(2), suggesting that eNOS activity may be higher at 21% O(2). Hence, the hyperoxia of in vitro EC flow studies, via increased NO and mitochondrial O(2)(*-) production, leads to enhanced ONOO(-) formation intramitochondrially and suppression of respiration.

  12. Determining Shear Stress Distribution in a Laminate

    NASA Technical Reports Server (NTRS)

    Bednarcyk, Brett A.; Aboudi, Jacob; Yarrington, Phillip W.

    2010-01-01

    A "simplified shear solution" method approximates the through-thickness shear stress distribution within a composite laminate based on an extension of laminated beam theory. The method does not consider the solution of a particular boundary value problem; rather, it requires only knowledge of the global shear loading, geometry, and material properties of the laminate or panel. It is thus analogous to lamination theory in that ply-level stresses can be efficiently determined from global load resultants at a given location in a structure and used to evaluate the margin of safety on a ply-by-ply basis. The simplified shear solution stress distribution is zero at free surfaces, continuous at ply boundaries, and integrates to the applied shear load. The method has been incorporated within the HyperSizer commercial structural sizing software to improve its predictive capability for designing composite structures. The HyperSizer structural sizing software is used extensively by NASA to design composite structures. In the case of through-thickness shear loading on panels, HyperSizer previously included a basic, industry-standard, method for approximating the resulting shear stress distribution in sandwich panels. However, no such method was employed for solid laminate panels. The purpose of the innovation is to provide an approximation of the through-thickness shear stresses in a solid laminate given the through-thickness shear loads (Qx and Qy) on the panel. The method was needed for implementation within the HyperSizer structural sizing software so that the approximated ply-level shear stresses could be utilized in a failure theory to assess the adequacy of a panel design. The simplified shear solution method was developed based on extending and generalizing bi-material beam theory to plate-like structures. It is assumed that the through-thickness shear stresses arise due to local bending of the laminate induced by the through-thickness shear load, and by imposing

  13. Impact of Bi-Axial Shear on Atherogenic Gene Expression by Endothelial Cells.

    PubMed

    Chakraborty, Amlan; Chakraborty, Sutirtha; Jala, Venkatakrishna R; Thomas, Jonathan M; Sharp, M Keith; Berson, R Eric; Haribabu, Bodduluri

    2016-10-01

    This study demonstrated the effects of the directionality of oscillatory wall shear stress (WSS) on proliferation and proatherogenic gene expression (I-CAM, E-Selectin, and IL-6) in the presence of inflammatory mediators leukotriene B4 (LTB4) and bacterial lipopolysaccharide (LPS) from endothelial cells grown in an orbiting culture dish. Computational fluid dynamics (CFD) was applied to quantify the flow in the dish, while an analytical solution representing an extension of Stokes second problem was used for validation. Results indicated that WSS magnitude was relatively constant near the center of the dish and oscillated significantly (0-0.9 Pa) near the side walls. Experiments showed that LTB4 dominated the shear effects on cell proliferation and area. Addition of LPS didn't change proliferation, but significantly affected cell area. The expression of I-CAM1, E-Selectin and IL-6 were altered by directional oscillatory shear index (DOSI, a measure of the biaxiality of oscillatory shear), but not shear magnitude. The significance of DOSI was further reinforced by the strength of its interactions with other atherogenic factors. Hence, directionality of shear appears to be an important factor in regulating gene expression and provides a potential explanation of the propensity for increased vascular lesions in regions in the arteries with oscillating biaxial flow.

  14. Turbulent shear stresses in compressible boundary layers

    NASA Technical Reports Server (NTRS)

    Laderman, A. J.; Demetriades, A.

    1979-01-01

    Hot-wire anemometer measurements of turbulent shear stresses in a Mach 3 compressible boundary layer were performed in order to investigate the effects of heat transfer on turbulence. Measurements were obtained by an x-probe in a flat plate, zero pressure gradient, two dimensional boundary layer in a wind tunnel with wall to freestream temperature ratios of 0.94 and 0.71. The measured shear stress distributions are found to be in good agreement with previous results, supporting the contention that the shear stress distribution is essentially independent of Mach number and heat transfer for Mach numbers from incompressible to hypersonic and wall to freestream temperature ratios of 0.4 to 1.0. It is also found that corrections for frequency response limitations of the electronic equipment are necessary to determine the correct shear stress distribution, particularly at the walls.

  15. Boundary Shear Stress Along Vegetated Streambanks

    NASA Astrophysics Data System (ADS)

    Clark, L. A.; Wynn, T.

    2007-12-01

    Sediment, a leading cause of water quality impairment, damages aquatic ecosystems and interferes with recreational uses and water treatment processes. Streambank retreat can contribute as much as 85% of watershed sediment yield. Vegetation is an important component of stream restoration designs used to control streambank retreat, but vegetation effects on streambank boundary shear stress (SBSS) need to be quantified. The overall goal of this experiment is to predict boundary shear stress along vegetated streambanks. This goal will be met by determining a method for measuring boundary shear stress in the field along hydraulically rough streambanks, evaluating the effects of streambank vegetation on boundary shear stress in the field, and developing predictive methods based on measurable vegetative properties. First, three streambank vegetation types (herbaceous, shrubbery, and woody) will be modeled in a flume study to examine both boundary shear stress measurement theory and instruments for field use. An appropriate method (law of the wall, Reynold's stresses, TKE, or average wall shear stress) and field instrument (ADV, propeller, or Pitot tube) will be selected, resulting in a field technique to measure SBSS. Predictive methods for estimating SBSS, based on common vegetation measurements, will be developed in the flume study and validated with field data. This research is intended to improve our understanding of the role of riparian vegetation in stream morphology by evaluating the effects of vegetation on boundary shear stress, providing insight to the type and density of vegetation required for streambank stability. The results will also aide in quantifying sediment inputs from streambanks, providing quantitative information for stream restoration projects and watershed management planning.

  16. PI16 is a shear stress and inflammation-regulated inhibitor of MMP2

    PubMed Central

    Hazell, Georgina G. J.; Peachey, Alasdair M. G.; Teasdale, Jack E.; Sala-Newby, Graciela B.; Angelini, Gianni D.; Newby, Andrew C.; White, Stephen J.

    2016-01-01

    Raised endothelial shear stress is protective against atherosclerosis but such protection may be lost at sites of inflammation. We found that four splice variants of the peptidase inhibitor 16 (PI16) mRNA are among the most highly shear stress regulated transcripts in human coronary artery endothelial cells (HCAECs), in vitro but that expression is reduced by inflammatory mediators TNFα and IL-1β. Immunohistochemistry demonstrated that PI16 is expressed in human coronary endothelium and in a subset of neointimal cells and medial smooth muscle cells. Adenovirus-mediated PI16 overexpression inhibits HCAEC migration and secreted matrix metalloproteinase (MMP) activity. Moreover, PI16 inhibits MMP2 in part by binding an exposed peptide loop above the active site. Our results imply that, at high endothelial shear stress, PI16 contributes to inhibition of protease activity; protection that can be reversed during inflammation. PMID:27996045

  17. Roles of cell confluency and fluid shear in 3-dimensional intracellular forces in endothelial cells.

    PubMed

    Hur, Sung Sik; del Álamo, Juan C; Park, Joon Seok; Li, Yi-Shuan; Nguyen, Hong A; Teng, Dayu; Wang, Kuei-Chun; Flores, Leona; Alonso-Latorre, Baldomero; Lasheras, Juan C; Chien, Shu

    2012-07-10

    We use a novel 3D inter-/intracellular force microscopy technique based on 3D traction force microscopy to measure the cell-cell junctional and intracellular tensions in subconfluent and confluent vascular endothelial cell (EC) monolayers under static and shear flow conditions. We found that z-direction cell-cell junctional tensions are higher in confluent EC monolayers than those in subconfluent ECs, which cannot be revealed in the previous 2D methods. Under static conditions, subconfluent cells are under spatially non-uniform tensions, whereas cells in confluent monolayers are under uniform tensions. The shear modulations of EC cytoskeletal remodeling, extracellular matrix (ECM) adhesions, and cell-cell junctions lead to significant changes in intracellular tensions. When a confluent monolayer is subjected to flow shear stresses with a high forward component comparable to that seen in the straight part of the arterial system, the intracellular and junction tensions preferentially increase along the flow direction over time, which may be related to the relocation of adherens junction proteins. The increases in intracellular tensions are shown to be a result of chemo-mechanical responses of the ECs under flow shear rather than a direct result of mechanical loading. In contrast, the intracellular tensions do not show a preferential orientation under oscillatory flow with a very low mean shear. These differences in the directionality and magnitude of intracellular tensions may modulate translation and transcription of ECs under different flow patterns, thus affecting their susceptibility for atherogenesis.

  18. 4D shear stress maps of the developing heart using Doppler optical coherence tomography.

    PubMed

    Peterson, Lindsy M; Jenkins, Michael W; Gu, Shi; Barwick, Lee; Watanabe, Michiko; Rollins, Andrew M

    2012-11-01

    Accurate imaging and measurement of hemodynamic forces is vital for investigating how physical forces acting on the embryonic heart are transduced and influence developmental pathways. Of particular importance is blood flow-induced shear stress, which influences gene expression by endothelial cells and potentially leads to congenital heart defects through abnormal heart looping, septation, and valvulogenesis. However no imaging tool has been available to measure shear stress on the endocardium volumetrically and dynamically. Using 4D structural and Doppler OCT imaging, we are able to accurately measure the blood flow in the heart tube in vivo and to map endocardial shear stress throughout the heart cycle under physiological conditions for the first time. These measurements of the shear stress patterns will enable precise titration of experimental perturbations and accurate correlation of shear with the expression of molecules critical to heart development.

  19. Methylglyoxal promotes oxidative stress and endothelial dysfunction.

    PubMed

    Sena, Cristina M; Matafome, Paulo; Crisóstomo, Joana; Rodrigues, Lisa; Fernandes, Rosa; Pereira, Paulo; Seiça, Raquel M

    2012-05-01

    Modern diets can cause modern diseases. Research has linked a metabolite of sugar, methylglyoxal (MG), to the development of diabetic complications, but the exact mechanism has not been fully elucidated. The present study was designed to investigate whether MG could directly influence endothelial function, oxidative stress and inflammation in Wistar and Goto-Kakizaki (GK) rats, an animal model of type 2 diabetes. Wistar and GK rats treated with MG in the drinking water for 3 months were compared with the respective control rats. The effects of MG were investigated on NO-dependent vasorelaxation in isolated rat aortic arteries from the different groups. Insulin resistance, NO bioavailability, glycation, a pro-inflammatory biomarker monocyte chemoattractant protein-1 (MCP-1) and vascular oxidative stress were also evaluated. Methylglyoxal treated Wistar rats significantly reduced the efficacy of NO-dependent vasorelaxation (p<0.001). This impairment was accompanied by a three fold increase in the oxidative stress marker nitrotyrosine. Advanced glycation endproducts (AGEs) formation was significantly increased as well as MCP-1 and the expression of the receptor for AGEs (RAGE). NO bioavailability was significantly attenuated and accompanied by an increase in superoxide anion immunofluorescence. Methylglyoxal treated GK rats significantly aggravated endothelial dysfunction, oxidative stress, AGEs accumulation and diminished NO bioavailability when compared with control GK rats. These results indicate that methylglyoxal induced endothelial dysfunction in normal Wistar rats and aggravated the endothelial dysfunction present in GK rats. The mechanism is at least in part by increasing oxidative stress and/or AGEs formation with a concomitant increment of inflammation and a decrement in NO bioavailability. The present study provides further evidence for methylglyoxal as one of the causative factors in the pathogenesis of atherosclerosis and development of macrovascular

  20. Integrated Shear Stress/Temperature Micromachined Sensors

    NASA Technical Reports Server (NTRS)

    Sheplak, Mark; Cattafesta, Louis N., III; Nishida, Toshikazu

    2002-01-01

    During this project we were able to design and initiate the fabrication of an integrated Micro ElectroMechanical Systems (MEMS)-based shear stress/temperature sensor for flow control applications. A brief summary of the completed activities during this project is presented.

  1. [Oxidative stress and endothelial dysfunction].

    PubMed

    Jarasūniene, Dalia; Simaitis, Audrius

    2003-01-01

    Growing numbers of morbidity and mortality due to the Coronary Heart Disease (CHD) is recognized as the more increasing challenge in the world. The initial stage of atherosclerosis, early diagnosis and treatment of CHD are the main objectives of current research. Endothelium dysfunction, the earliest expression of the atherosclerotic process is associated with subtle biochemical changes that gradually are transformed into the structural changes of the arterial wall. The theory of free radicals is the most common among the atherosclerosis explanations. Overproduction or impaired neutralization of the free radicals accounts for oxidative stress that is causing substantial damage to the low density lipoproteins, nitric oxyde (NO), endothelium cells, tissue cells and finally leads to the endothelium dysfuction. Pathophysiology of oxidative stress and its role in the endothelium dysfunction are discussed in this paper. Positive role of various medications (statins, angiotensin converting enzym inhibitors, aldosteron antagonists, estrogens, antioxidants, b-blockers with vasodilatative properties) to the oxidative stress and consequently to the endothelium dysfuction are discussed as well.

  2. Retrograde shear rate in formerly preeclamptic and healthy women before and after exercise training: relationship with endothelial function.

    PubMed

    Scholten, Ralph R; Spaanderman, Marc E A; Green, Daniel J; Hopman, Maria T E; Thijssen, Dick H J

    2014-08-01

    Blood flow patterns in conduit arteries characterized by high levels of retrograde shear stress can be detrimental for vascular health. In this study we examined whether retrograde shear rate and endothelial function are related in healthy and formerly preeclamptic (PE) women and whether this relationship is altered by exercise training. Formerly PE women (32 ± 4 yr, n = 20) and controls (32 ± 4 yr, n = 20), all 6-12 mo postpartum, performed 12-wk aerobic exercise training. We measured brachial artery shear rate (SR) and endothelial function by flow-mediated dilation (FMD, echo-Doppler). We additionally performed power spectral analysis of heart rate variability and calculated low-frequency/high-frequency (LF/HF) ratio. Antegrade SR was not different between groups, while retrograde SR was significantly higher and FMD% lower in PE women compared with controls (both P < 0.05). Retrograde shear correlated strongly with FMD% in PE women and controls (P < 0.05). LF/HF ratio inversely correlated with brachial artery retrograde SR and FMD% (both P < 0.05) in PE women and controls. Exercise training reduced retrograde shear, improved FMD%, and reduced LF/HF ratios similarly in both groups (all P < 0.05). Training-induced changes in retrograde SR correlated with changes in FMD% and LF/HF ratio. A higher brachial artery retrograde SR relates to lower brachial artery endothelial function, in both controls and formerly PE women. Exercise training improves retrograde SR, while the magnitude of this change correlated strongly with improvements in FMD and reductions in LF/HF ratio. Therefore, the impact of PE and exercise training on endothelial health may, at least partly, be related to retrograde shear rate.

  3. Animal models of surgically manipulated flow velocities to study shear stress-induced atherosclerosis.

    PubMed

    Winkel, Leah C; Hoogendoorn, Ayla; Xing, Ruoyu; Wentzel, Jolanda J; Van der Heiden, Kim

    2015-07-01

    Atherosclerosis is a chronic inflammatory disease of the arterial tree that develops at predisposed sites, coinciding with locations that are exposed to low or oscillating shear stress. Manipulating flow velocity, and concomitantly shear stress, has proven adequate to promote endothelial activation and subsequent plaque formation in animals. In this article, we will give an overview of the animal models that have been designed to study the causal relationship between shear stress and atherosclerosis by surgically manipulating blood flow velocity profiles. These surgically manipulated models include arteriovenous fistulas, vascular grafts, arterial ligation, and perivascular devices. We review these models of manipulated blood flow velocity from an engineering and biological perspective, focusing on the shear stress profiles they induce and the vascular pathology that is observed.

  4. Flexible Micropost Arrays for Shear Stress Measurement

    NASA Technical Reports Server (NTRS)

    Wohl, Christopher J.; Palmieri, Frank L.; Hopkins, John W.; Jackson, Allen M.; Connell, John W.; Lin, Yi; Cisotto, Alexxandra A.

    2015-01-01

    Increased fuel costs, heightened environmental protection requirements, and noise abatement continue to place drag reduction at the forefront of aerospace research priorities. Unfortunately, shortfalls still exist in the fundamental understanding of boundary-layer airflow over aerodynamic surfaces, especially regarding drag arising from skin friction. For example, there is insufficient availability of instrumentation to adequately characterize complex flows with strong pressure gradients, heat transfer, wall mass flux, three-dimensionality, separation, shock waves, and transient phenomena. One example is the acoustic liner efficacy on aircraft engine nacelle walls. Active measurement of shear stress in boundary layer airflow would enable a better understanding of how aircraft structure and flight dynamics affect skin friction. Current shear stress measurement techniques suffer from reliability, complexity, and airflow disruption, thereby compromising resultant shear stress data. The state-of-the-art for shear stress sensing uses indirect or direct measurement techniques. Indirect measurements (e.g., hot-wire, heat flux gages, oil interferometry, laser Doppler anemometry, small scale pressure drag surfaces, i.e., fences) require intricate knowledge of the studied flow, restrictive instrument arrangements, large surface areas, flow disruption, or seeding material; with smaller, higher bandwidth probes under development. Direct measurements involve strain displacement of a sensor element and require no prior knowledge of the flow. Unfortunately, conventional "floating" recessed components for direct measurements are mm to cm in size. Whispering gallery mode devices and Fiber Bragg Gratings are examples of recent additions to this type of sensor with much smaller (?m) sensor components. Direct detection techniques are often single point measurements and difficult to calibrate and implement in wind tunnel experiments. In addition, the wiring, packaging, and installation

  5. APPLYING SHEAR STRESS TO PLURIPOTENT STEM CELLS

    PubMed Central

    Wolfe, Russell P.; Guidry, Julia B.; Messina, Stephanie L.; Ahsan, Tabassum

    2016-01-01

    Summary Thorough understanding of the effects of shear stress on stem cells is critical for the rationale design of large-scale production of cell-based therapies. This is of growing importance as emerging tissue engineering and regenerative medicine applications drive the need for clinically-relevant numbers of both pluripotent stem cells (PSCs) and cells derived from PSCs. Here we describe the use of a custom parallel plate bioreactor system to impose fluid shear stress on a layer of PSCs adhered to protein-coated glass slides. This system can be useful both for basic science studies in mechanotransduction and as a surrogate model for bioreactors used in large-scale production. PMID:25762292

  6. Effect of shear stress on migration and integrin expression in macaque trophoblast cells.

    PubMed

    Soghomonians, Arlen; Barakat, Abdul I; Thirkill, Twanda L; Blankenship, Thomas N; Douglas, Gordon C

    2002-05-08

    During fetal development, trophoblast cells enter endometrial capillaries, migrate within the uterine vasculature, and eventually reside within spiral arteries of the uterus. This invasive activity is accompanied by upregulation of trophoblast beta1 integrin expression. Fluid mechanical shear stress regulates migration and expression of adhesion molecules in vascular endothelial cells, but nothing is known about the effects of shear stress on trophoblast cells. We tested the hypothesis that shear stress regulates the motility and beta1 integrin expression of trophoblast cells. Early gestation macaque trophoblast cells were cultured in 1 x 1-mm square cross-section capillary tubes within which the flow field was determined using three-dimensional computational fluid dynamic simulations. Trophoblast cells in the capillary tubes were exposed to a steady shear stress of 7.5, 15, or 30 dyn/cm2 for up to 24 h. In the absence of flow, trophoblast cells were highly dynamic with constant nondirectional positional shifts but with no net cell migration. Exposure of the cells to shear stress within 24-72 h of cell plating significantly increased the level of this activity and led to net cell migration in the direction of flow. Shear stress also increased the expression and altered the topography of beta1 integrin. These results suggest that shear stress regulates trophoblast motility and beta1 integrin expression in vitro.

  7. Shear stress-induced NO production is dependent on ATP autocrine signaling and capacitative calcium entry

    PubMed Central

    Andrews, Allison M.; Jaron, Dov; Buerk, Donald G.; Barbee, Kenneth A.

    2014-01-01

    Flow-induced production of nitric oxide (NO) by endothelial cells plays a fundamental role in vascular homeostasis. However, the mechanisms by which shear stress activates NO production remain unclear due in part to limitations in measuring NO, especially under flow conditions. Shear stress elicits the release of ATP, but the relative contribution of autocrine stimulation by ATP to flow-induced NO production has not been established. Furthermore, the importance of calcium in shear stress-induced NO production remains controversial, and in particular the role of capacitive calcium entry (CCE) has yet to be determined. We have utilized our unique NO measurement device to investigate the role of ATP autocrine signaling and CCE in shear stress-induced NO production. We found that endogenously released ATP and downstream activation of purinergic receptors and CCE plays a significant role in shear stress-induced NO production. ATP-induced eNOS phophorylation under static conditions is also dependent on CCE. Inhibition of protein kinase C significantly inhibited eNOS phosphorylation and the calcium response. To our knowledge, we are the first to report on the role of CCE in the mechanism of acute shear stress-induced NO response. In addition, our work highlights the importance of ATP autocrine signaling in shear stress-induced NO production. PMID:25386222

  8. Stent implantation influence wall shear stress evolution

    NASA Astrophysics Data System (ADS)

    Bernad, S. I.; Totorean, A. F.; Bosioc, A. I.; Petre, I.; Bernad, E. S.

    2016-06-01

    Local hemodynamic factors are known affect the natural history of the restenosis critically after coronary stenting of atherosclerosis. Stent-induced flows disturbance magnitude dependent directly on the strut design. The impact of flow alterations around struts vary as the strut geometrical parameters change. Our results provide data regarding the hemodynamic parameters for the blood flow in both stenosed and stented coronary artery under physiological conditions, namely wall shear stress and pressure drop.

  9. Shear Stress Sensing using Elastomer Micropillar Arrays

    NASA Technical Reports Server (NTRS)

    Wohl, Christopher J.; Palmieri, Frank L.; Lin, Yi; Jackson, Allen M.; Cissoto, Alexxandra; Sheplak, Mark; Connell, John W.

    2013-01-01

    The measurement of shear stress developed as a fluid moves around a solid body is difficult to measure. Stresses at the fluid-solid interface are very small and the nature of the fluid flow is easily disturbed by introducing sensor components to the interface. To address these challenges, an array of direct and indirect techniques have been investigated with various advantages and challenges. Hot wire sensors and other indirect sensors all protrude significantly into the fluid flow. Microelectromechanical systems (MEMS) devices, although facilitating very accurate measurements, are not durable, are prone to contamination, and are difficult to implement into existing model geometries. One promising approach is the use of engineered surfaces that interact with fluid flow in a detectable manner. To this end, standard lithographic techniques have been utilized to generate elastomeric micropillar arrays of various lengths and diameters. Micropillars of controlled length and width were generated in polydimethylsiloxane (PDMS) elastomer using a soft-lithography technique. The 3D mold for micropillar replication was fabricated using laser ablative micromachining and contact lithography. Micropillar dimensions and mechanical properties were characterized and compared to shear sensing requirements. The results of this characterization as well as shear stress detection techniques will be discussed.

  10. The shear stress of it all: the cell membrane and mechanochemical transduction.

    PubMed

    White, Charles R; Frangos, John A

    2007-08-29

    As the inner lining of the vessel wall, vascular endothelial cells are poised to act as a signal transduction interface between haemodynamic forces and the underlying vascular smooth-muscle cells. Detailed analyses of fluid mechanics in atherosclerosis-susceptible regions of the vasculature reveal a strong correlation between endothelial cell dysfunction and areas of low mean shear stress and oscillatory flow with flow recirculation. Conversely, steady shear stress stimulates cellular responses that are essential for endothelial cell function and are atheroprotective. The molecular basis of shear-induced mechanochemical signal transduction and the endothelium's ability to discriminate between flow profiles remains largely unclear. Given that fluid shear stress does not involve a traditional receptor/ligand interaction, identification of the molecule(s) responsible for sensing fluid flow and mechanical force discrimination has been difficult. This review will provide an overview of the haemodynamic forces experienced by the vascular endothelium and its role in localizing atherosclerotic lesions within specific regions of the vasculature. Also reviewed are several recent lines of evidence suggesting that both changes in membrane microviscosity linked to heterotrimeric G proteins, and the transmission of tension across the cell membrane to the cell-cell junction where known shear-sensitive proteins are localized, may serve as the primary force-sensing elements of the cell.

  11. Interaction of wall shear stress magnitude and gradient in the prediction of arterial macromolecular permeability.

    PubMed

    LaMack, Jeffrey A; Himburg, Heather A; Li, Xue-Mei; Friedman, Morton H

    2005-04-01

    Large spatial shear stress gradients have anecdotally been associated with early atherosclerotic lesion susceptibility in vivo and have been proposed as promoters of endothelial cell dysfunction in vitro. Here, experiments are presented in which several measures of the fluid dynamic shear stress, including its gradient, at the walls of in vivo porcine iliac arteries, are correlated against the transendothelial macromolecular permeability of the vessels. The fluid dynamic measurements are based on postmortem vascular casts, and permeability is measured from Evans blue dye (EBD) uptake. Time-averaged wall shear stress (WSS), as well as a new parameter termed maximum gradient stress (MGS) that describes the spatial shear stress gradient due to flow acceleration at a given point, are mapped for each artery and compared on a point-by-point basis to the corresponding EBD patterns. While there was no apparent relation between MGS and EBD uptake, a composite parameter, WSS(-0.11) MGS(0.044), was highly correlated with permeability. Notwithstanding the small exponents, the parameter varied widely within the region of interest. The results suggest that sites exposed to low wall shear stresses are more likely to exhibit elevated permeability, and that this increase is exacerbated in the presence of large spatial shear stress gradients.

  12. Wrinkling of reinforced plates subjected to shear stresses

    NASA Technical Reports Server (NTRS)

    Seydel, Edgar

    1931-01-01

    An analysis is made here of the problem of long plates with transverse stiffeners subject to shear. A typical example would be a long Wagner beam. The shear stress is calculated at which the web wrinkles and shear stress becomes a maximum. The equation is solved for both a condition of free support and rigidity of support on the edges.

  13. A microfluidic cell culture system for monitoring of sequential changes in endothelial cells after heat stress.

    PubMed

    Tazawa, Hidekatsu; Sato, Kenjiro; Tsutiya, Atsuhiro; Tokeshi, Manabu; Ohtani-Kaneko, Ritsuko

    2015-08-01

    Endothelial damage induced by a highly elevated body temperature is crucial in some diseases including viral hemorrhagic fevers. Here, we report the heat-induced sequential changes of endothelial cells under shear stress, which were determined with a microfluidic culture system. Although live cell imaging showed only minor changes in the appearance of heat-treated cells, Hsp70 mRNA expression analysis demonstrated that the endothelial cells in channels of the system responded well to heat treatment. F-actin staining also revealed clear changes in the bundles of actin filaments after heat treatment. Well-organized bundles of actin filaments in control cells disappeared in heat-treated cells cultured in the channel. Furthermore, the system enabled detection of sequential changes in plasminogen activator inhibitor-1 (PAI-1) secretion from endothelial cells. PAI-1 concentration in the effluent solution was significantly elevated for the first 15min after initiation of heat treatment, and then decreased subsequently. This study provides fundamental information on heat-induced endothelial changes under shear stress and introduces a potent tool for analyzing endothelial secretions.

  14. Lubricant limiting shear stress effect on EHD film thickness

    NASA Technical Reports Server (NTRS)

    Gecim, B.; Winer, W. O.

    1979-01-01

    A Grubin-like EHD inlet analysis utilizing a non-linear viscous fluid model with a limiting shear stress is reported. The shear rheological equation requirs only a low shear stress viscosity and the limiting shear stress both functions of pressure. Values employed for these properties are taken from measurements on typical lubricants. Reductions of EHD film thickness are found to be up to 40 percent compared with the standard Grubin prediction for typical operating conditions. Slide-roll ratio, limiting shear stress dependence on pressure, and atmospheric pressure value of limiting shear stress are new variables required to determine film thickness with the first two being more important than the last. The EHD film thickness is reduced by increasing slide-roll ratio and/or decreasing the pressure dependence of the limiting shear stress.

  15. Shear stress cleaning for surface departiculation

    NASA Technical Reports Server (NTRS)

    Musselman, R. P.; Yarbrough, T. W.

    1986-01-01

    A cleaning technique widely used by the nuclear utility industry for removal of radioactive surface contamination has proven effective at removing non-hazardous contaminant particles as small as 0.1 micrometer. The process employs a controlled high velocity liquid spray inside a vapor containment enclosure to remove particles from a surface. The viscous drag force generated by the cleaning fluid applies a shear stress greater than the adhesion force that holds small particles to a substrate. Fluid mechanics and field tests indicate general cleaning parameters.

  16. Shear-stress relaxation and ensemble transformation of shear-stress autocorrelation functions

    NASA Astrophysics Data System (ADS)

    Wittmer, J. P.; Xu, H.; Baschnagel, J.

    2015-02-01

    We revisit the relation between the shear-stress relaxation modulus G (t ) , computed at finite shear strain 0 <γ ≪1 , and the shear-stress autocorrelation functions C(t ) | γ and C(t ) | τ computed, respectively, at imposed strain γ and mean stress τ . Focusing on permanent isotropic spring networks it is shown theoretically and computationally that in general G(t ) =C (t ) | τ=C(t ) | γ+Geq for t >0 with Geq being the static equilibrium shear modulus. G (t ) and C(t ) | γ thus must become different for solids and it is impossible to obtain Geq alone from C(t ) | γ as often assumed. We comment briefly on self-assembled transient networks where Geq(f ) must vanish for a finite scission-recombination frequency f . We argue that G(t ) =C (t ) | τ=C(t ) | γ should reveal an intermediate plateau set by the shear modulus Geq(f =0 ) of the quenched network.

  17. Mesenchymal stem cells exhibit firm adhesion, crawling, spreading and transmigration across aortic endothelial cells: effects of chemokines and shear.

    PubMed

    Chamberlain, Giselle; Smith, Helen; Rainger, G Ed; Middleton, Jim

    2011-01-01

    Mesenchymal stem cells (MSCs) have anti-inflammatory and immunosuppressive properties and may be useful in the therapy of diseases such as arteriosclerosis. MSCs have some ability to traffic into inflamed tissues, however to exploit this therapeutically their migratory mechanisms need to be elucidated. This study examines the interaction of murine MSCs (mMSCs) with, and their migration across, murine aortic endothelial cells (MAECs), and the effects of chemokines and shear stress. The interaction of mMSCs with MAECs was examined under physiological flow conditions. mMSCs showed lack of interaction with MAECs under continuous flow. However, when the flow was stopped (for 10 min) and then started, mMSCs adhered and crawled on the endothelial surface, extending fine microvillous processes (filopodia). They then spread extending pseudopodia in multiple directions. CXCL9 significantly enhanced the percentage of mMSCs adhering, crawling and spreading and shear forces markedly stimulated crawling and spreading. CXCL9, CXCL16, CCL20 and CCL25 significantly enhanced transendothelial migration across MAECs. The transmigrated mMSCs had down-regulated receptors CXCR3, CXCR6, CCR6 and CCR9. This study furthers the knowledge of MSC transendothelial migration and the effects of chemokines and shear stress which is of relevance to inflammatory diseases such as arteriosclerosis.

  18. Physiological mechanisms of vascular response induced by shear stress and effect of exercise in systemic and placental circulation

    PubMed Central

    Rodríguez, Iván; González, Marcelo

    2014-01-01

    Physiological vascular function regulation is essential for cardiovascular health and depends on adequate control of molecular mechanisms triggered by endothelial cells in response to mechanical and chemical stimuli induced by blood flow. Endothelial dysfunction is one of the main risk factors of cardiovascular pathology, where the imbalance between the synthesis of vasodilator and vasoconstrictor molecules is common in the development of vascular disorders in systemic and placental circulation. In the placenta, an organ without autonomic innervations, the local control of vascular tone is critical for maintenance of fetal growth and mechanisms that underlie shear stress response induced by blood flow are essential during pregnancy. In this field, shear stress induced by moderate exercise is one of the most important mechanisms to improve vascular function through nitric oxide synthesis and stimulation of mechanical response of endothelial cells triggered by ion channels, caveolae, endothelial NO synthase, and vascular endothelial growth factor, among others. The demand for oxygen and nutrients by tissues and organs, especially in placentation and pregnancy, determines blood flow parameters, and physiological adaptations of vascular beds for covering metabolic requirements. In this regard, moderate exercise versus sedentarism shows potential benefits for improving vascular function associated with the enhancement of molecular mechanisms induced by shear stress. In this review, we collect evidence about molecular bases of physiological response to shear stress in order to highlight the relevance of moderate exercise-training for vascular health in adult and fetal life. PMID:25278895

  19. Colors Of Liquid Crystals Used To Measure Surface Shear Stresses

    NASA Technical Reports Server (NTRS)

    Reda, D. C.; Muratore, J. J., Jr.

    1996-01-01

    Developmental method of mapping shear stresses on aerodynamic surfaces involves observation, at multiple viewing angles, of colors of liquid-crystal surface coats illuminated by white light. Report describing method referenced in "Liquid Crystals Indicate Directions Of Surface Shear Stresses" (ARC-13379). Resulting maps of surface shear stresses contain valuable data on magnitudes and directions of skin friction forces associated with surface flows; data used to refine mathematical models of aerodynamics for research and design purposes.

  20. Wall shear stress estimates in coronary artery constrictions

    NASA Technical Reports Server (NTRS)

    Back, L. H.; Crawford, D. W.

    1992-01-01

    Wall shear stress estimates from laminar boundary layer theory were found to agree fairly well with the magnitude of shear stress levels along coronary artery constrictions obtained from solutions of the Navier Stokes equations for both steady and pulsatile flow. The relatively simple method can be used for in vivo estimates of wall shear stress in constrictions by using a vessel shape function determined from a coronary angiogram, along with a knowledge of the flow rate.

  1. 4-Dimensional light-sheet microscopy to elucidate shear stress modulation of cardiac trabeculation.

    PubMed

    Lee, Juhyun; Fei, Peng; Packard, René R Sevag; Kang, Hanul; Xu, Hao; Baek, Kyung In; Jen, Nelson; Chen, Junjie; Yen, Hilary; Kuo, C-C Jay; Chi, Neil C; Ho, Chih-Ming; Li, Rongsong; Hsiai, Tzung K

    2016-05-02

    Hemodynamic shear forces are intimately linked with cardiac development, during which trabeculae form a network of branching outgrowths from the myocardium. Mutations that alter Notch signaling also result in trabeculation defects. Here, we assessed whether shear stress modulates trabeculation to influence contractile function. Specifically, we acquired 4D (3D + time) images with light sheets by selective plane illumination microscopy (SPIM) for rapid scanning and deep axial penetration during zebrafish morphogenesis. Reduction of blood viscosity via gata1a morpholino oligonucleotides (MO) reduced shear stress, resulting in downregulation of Notch signaling and attenuation of trabeculation. Arrest of cardiomyocyte contraction either by troponin T type 2a (tnnt2a) MO or in weak atriumm58 (wea) mutants resulted in reduced shear stress and downregulation of Notch signaling and trabeculation. Integrating 4D SPIM imaging with synchronization algorithm demonstrated that coinjection of neuregulin1 mRNA with gata1 MO rescued trabeculation to restore contractile function in association with upregulation of Notch-related genes. Crossbreeding of Tg(flk:mCherry) fish, which allows visualization of the vascular system with the Tg(tp1:gfp) Notch reporter line, revealed that shear stress-mediated Notch activation localizes to the endocardium. Deleting endocardium via the clochesk4 mutants downregulated Notch signaling, resulting in nontrabeculated ventricle. Subjecting endothelial cells to pulsatile flow in the presence of the ADAM10 inhibitor corroborated shear stress-activated Notch signaling to modulate trabeculation.

  2. Actin Filament Stress Fibers in Vascular Endothelial Cells in vivo

    NASA Astrophysics Data System (ADS)

    Wong, Albert J.; Pollard, Thomas D.; Herman, Ira M.

    1983-02-01

    Fluorescence microscopy with 7-nitrobenz-2-oxa-3-diazole phallacidin was used to survey vertebrate tissues for actin filament bundles comparable to the stress fibers of cultured cells. Such bundles were found only in vascular endothelial cells. Like the stress fibers of cultured cells, these actin filament bundles were stained in a punctate pattern by fluorescent antibodies to both alpha-actinin and myosin. The stress fibers were oriented parallel to the direction of blood flow and were prominent in endothelial cells from regions exposed to high-velocity flow, such as the left ventricle, aortic valve, and aorta. Actin bundles may help the endothelial cell to withstand hemodynamic stress.

  3. Role of hemodynamic shear stress in cardiovascular disease.

    PubMed

    Cecchi, Emanuele; Giglioli, Cristina; Valente, Serafina; Lazzeri, Chiara; Gensini, Gian Franco; Abbate, Rosanna; Mannini, Lucia

    2011-02-01

    Atherosclerosis is the main cause of morbidity and mortality in the Western world. Inflammation and blood flow alterations are new markers emerging as possible determinants for the development of atherosclerotic lesions. In particular, blood flow exerts a shear stress on vessel walls that alters cell physiology. Shear stress arises from the friction between two virtual layers of a fluid and is induced by the difference in motion and viscosity between these layers. Regions of the arterial tree with uniform geometry are exposed to a unidirectional and constant flow, which determines a physiologic shear stress, while arches and bifurcations are exposed to an oscillatory and disturbed flow, which determines a low shear stress. Atherosclerotic lesions develop mainly in areas of low shear stress, while those exposed to a physiologic shear stress are protected. The presence of areas of the arterial tree with different wall shear stress may explain, in part, the different localization of atherosclerotic lesions in both coronary and extracoronary arteries. The measurement of this parameter may help in identifying atherosclerotic plaques at higher risk as well as in evaluating the efficacy of different pharmacological interventions. Moreover, an altered shear stress is associated with the occurrence of both aortic and intracranial aneurysms, possibly leading to their growth and rupture. Finally, the evaluation of shear stress may be useful for predicting the risk of developing restenosis after coronary and peripheral angioplasty and for devising a coronary stent with a strut design less thrombogenic and more conducive to endothelization.

  4. Adjustable shear stress erosion and transport flume

    DOEpatents

    Roberts, Jesse D.; Jepsen, Richard A.

    2002-01-01

    A method and apparatus for measuring the total erosion rate and downstream transport of suspended and bedload sediments using an adjustable shear stress erosion and transport (ASSET) flume with a variable-depth sediment core sample. Water is forced past a variable-depth sediment core sample in a closed channel, eroding sediments, and introducing suspended and bedload sediments into the flow stream. The core sample is continuously pushed into the flow stream, while keeping the surface level with the bottom of the channel. Eroded bedload sediments are transported downstream and then gravitationally separated from the flow stream into one or more quiescent traps. The captured bedload sediments (particles and aggregates) are weighed and compared to the total mass of sediment eroded, and also to the concentration of sediments suspended in the flow stream.

  5. On stress collapse in adiabatic shear bands

    NASA Astrophysics Data System (ADS)

    Wright, T. W.; Walter, J. W.

    T HE DYNAMICS of adiabatic shear band formation is considered making use of a simplified thermo/visco/plastic flow law. A new numerical solution is used to follow the growth of a perturbation from initiation, through early growth and severe localization, to a slowly varying terminal configuration. Asymptotic analyses predict the early and late stage patterns, but the timing and structure of the abrupt transition to severe localization can only be studied numerically, to date. A characteristic feature of the process is that temperature and plastic strain rate begin to localize immediately, but only slowly, whereas the stress first evolves almost as if there were no perturbation, but then collapses rapidly when severe localization occurs.

  6. Two-axis direct fluid shear stress sensor

    NASA Technical Reports Server (NTRS)

    Bajikar, Sateesh (Inventor); Scott, Michael A. (Inventor); Adcock, Edward E. (Inventor)

    2011-01-01

    A micro sized multi-axis semiconductor skin friction/wall shear stress induced by fluid flow. The sensor design includes a shear/strain transduction gimble connected to a force collecting plate located at the flow boundary surface. The shear force collecting plate is interconnected by an arm to offset the tortional hinges from the fluid flow. The arm is connected to the shear force collecting plate through dual axis torsional hinges with piezoresistive torsional strain gauges. These gauges are disposed on the tortional hinges and provide a voltage output indicative of applied shear stress acting on the force collection plate proximate the flow boundary surface. Offsetting the torsional hinges creates a force concentration and resolution structure that enables the generation of a large stress on the strain gauge from small shear stress, or small displacement of the collecting plate. The design also isolates the torsional sensors from exposure to the fluid flow.

  7. Chronic high blood flow potentiates shear stress-induced release of NO in arteries of aged rats

    PubMed Central

    Yan, Changdong; Huang, An; Kaley, Gabor; Sun, Dong

    2011-01-01

    Aging impairs shear-stress-dependent dilation of arteries via increased superoxide production, decreased SOD activity, and decreased activation of endothelial nitric oxide (NO) synthase (eNOS). In the present study, we investigated whether chronic increases in shear stress, elicited by increases in blood flow, would improve vascular endothelial function of aged rats. To this end, second-order mesenteric arteries of young (6 mo) and aged (24 mo) male Fischer-344 rats were selectively ligated for 3 wk to elevate blood flow in a first-order artery [high blood flow (HF)]. An in vitro study was then conducted on first-order arteries with HF and normal blood flow (NF) to assess shear stress (1, 10, and 20 dyn/cm2)-induced release of NO into the perfusate. In HF arteries of both age groups, shear stress-induced NO production increased significantly. In 24-mo-old rats, the reduced shear stress-induced NO production in NF arteries was normalized by HF to a level similar to that in NF arteries of 6-mo-old rats. The increased NO production in HF arteries of 24-mo-old rats was associated with increased shear stress-induced dilation, expression of eNOS protein, and shear stress-induced eNOS phosphorylation. Wortmannin, a phosphatidylinositol 3-kinase inhibitor, reduced shear stress-induced eNOS phosphorylation and vasodilation. Superoxide production decreased significantly in HF compared with NF arteries in 24-mo-old rats. The decreased superoxide production was associated with significant increases in CuZn-SOD and extracellular SOD protein expressions and total SOD activity. These results suggest that stimulation with chronic HF restores shear-stress-induced activation of eNOS and antioxidant ability in aged arteries. PMID:17873019

  8. A model of Barchan dunes including lateral shear stress.

    PubMed

    Schwämmle, V; Herrmann, H J

    2005-01-01

    Barchan dunes are found where sand availability is low and wind direction quite constant. The two dimensional shear stress of the wind field and the sand movement by saltation and avalanches over a barchan dune are simulated. The model with one dimensional shear stress is extended including surface diffusion and lateral shear stress. The resulting final shape is compared to the results of the model with a one dimensional shear stress and confirmed by comparison to measurements. We found agreement and improvements with respect to the model with one dimensional shear stress. Additionally, a characteristic edge at the center of the windward side is discovered which is also observed for big barchans. Diffusion effects reduce this effect for small dunes.

  9. Nitrogen-rich plasma-polymerized coatings on PET and PTFE surfaces improve endothelial cell attachment and resistance to shear flow.

    PubMed

    Gigout, Anne; Ruiz, Juan-Carlos; Wertheimer, Michael R; Jolicoeur, Mario; Lerouge, Sophie

    2011-08-11

    Low seeding efficiency and poor cell retention under flow-induced shear stress limit the effectiveness of in vitro endothelialization strategies for small-diameter vascular grafts. Primary-amine-rich plasma-polymerized coatings (PPE:N) deposited using low- and atmospheric-pressure plasma discharges on PET and PTFE are evaluated for their ability to improve endothelial cells' kinetics and strength of attachment. PPE:N coatings increase cell adhesion and adhesion rate, spreading, focal adhesion, and resistance to flow-induced shear compared with bare and gelatin-coated PET and PTFE. In particular, about 90% of the cells remain on coated surfaces after 1 h exposure to shear. These coatings, therefore, appear as a promising versatile approach to improve cell seeding strategies for vascular grafts.

  10. The shear-stress intensity factor for a centrally cracked stiff-flanged shear web

    NASA Technical Reports Server (NTRS)

    Fichter, W. B.

    1976-01-01

    By use of the principle of superposition the stiff-flanged shear web is modeled mathematically by an infinite elastic strip with fixed longitudinal edges. The shear-stress intensity factor for a central longitudinal crack is calculated for various values of the ratio of strip width to crack length, h/a, in the range 0.1-10. The interaction of the crack with the boundaries is illustrated by boundary shear-stress distributions for three values of h/a. Some implications of the results for the design of damage-tolerant shear webs are discussed briefly.

  11. 4-Dimensional light-sheet microscopy to elucidate shear stress modulation of cardiac trabeculation

    PubMed Central

    Lee, Juhyun; Fei, Peng; Packard, René R. Sevag; Kang, Hanul; Xu, Hao; Baek, Kyung In; Jen, Nelson; Chen, Junjie; Yen, Hilary; Chi, Neil C.; Ho, Chih-Ming; Hsiai, Tzung K.

    2016-01-01

    Hemodynamic shear forces are intimately linked with cardiac development, during which trabeculae form a network of branching outgrowths from the myocardium. Mutations that alter Notch signaling also result in trabeculation defects. Here, we assessed whether shear stress modulates trabeculation to influence contractile function. Specifically, we acquired 4D (3D + time) images with light sheets by selective plane illumination microscopy (SPIM) for rapid scanning and deep axial penetration during zebrafish morphogenesis. Reduction of blood viscosity via gata1a morpholino oligonucleotides (MO) reduced shear stress, resulting in downregulation of Notch signaling and attenuation of trabeculation. Arrest of cardiomyocyte contraction either by troponin T type 2a (tnnt2a) MO or in weak atriumm58 (wea) mutants resulted in reduced shear stress and downregulation of Notch signaling and trabeculation. Integrating 4D SPIM imaging with synchronization algorithm demonstrated that coinjection of neuregulin1 mRNA with gata1 MO rescued trabeculation to restore contractile function in association with upregulation of Notch-related genes. Crossbreeding of Tg(flk:mCherry) fish, which allows visualization of the vascular system with the Tg(tp1:gfp) Notch reporter line, revealed that shear stress–mediated Notch activation localizes to the endocardium. Deleting endocardium via the clochesk4 mutants downregulated Notch signaling, resulting in nontrabeculated ventricle. Subjecting endothelial cells to pulsatile flow in the presence of the ADAM10 inhibitor corroborated shear stress–activated Notch signaling to modulate trabeculation. PMID:27018592

  12. Inhibition of c-Jun N-terminal kinase attenuates low shear stress-induced atherogenesis in apolipoprotein E-deficient mice.

    PubMed

    Wang, Juan; An, Feng Shuang; Zhang, Wei; Gong, Lei; Wei, Shu Jian; Qin, Wei Dong; Wang, Xu Ping; Zhao, Yu Xia; Zhang, Yun; Zhang, Cheng; Zhang, Ming-Xiang

    2011-01-01

    Atherosclerosis begins as local inflammation of arterial walls at sites of disturbed flow, such as vessel curvatures and bifurcations with low shear stress. c-Jun NH₂-terminal kinase (JNK) is a major regulator of flow-dependent gene expression in endothelial cells in atherosclerosis. However, little is known about the in vivo role of JNK in low shear stress in atherosclerosis. We aimed to observe the effect of JNK on low shear stress-induced atherogenesis in apolipoprotein E-deficient (ApoE(-/-)) mice and investigate the potential mechanism in human umbilical vein endothelial cells (HUVECs). We divided 84 male ApoE(-/-) mice into two groups for treatment with normal saline (NS) (n = 42) and JNK inhibitor SP600125 (JNK-I) (n = 42). Perivascular shear stress modifiers were placed around the right carotid arteries, and plaque formation was studied at low shear stress regions. The left carotid arteries without modifiers represented undisturbed shear stress as a control. The NS group showed atherosclerotic lesions in arterial regions with low shear stress, whereas the JNK-I group showed almost no atherosclerotic lesions. Corresponding to the expression of proatherogenic vascular cell adhesion molecule 1 (VCAM-1), phospho-JNK (p-JNK) level was higher in low shear stress regions with NS than with JNK-I inhibitor. In HUVECs under low shear stress, siRNA knockdown and SP600125 inhibition of JNK attenuated nuclear factor (NF)-κB activity and VCAM-1 expression. Furthermore, siRNA knockdown of platelet endothelial cell adhesion molecule 1 (PECAM-1) (CD31) reduced p-JNK and VCAM-1 levels after low shear stress stimulation. JNK may play a critical role in low shear stress-induced atherogenesis by a PECAM-1-dependent mechanosensory pathway and modulating NF-κB activity and VCAM-1 expression.

  13. Flow-activated chloride channels in vascular endothelium. Shear stress sensitivity, desensitization dynamics, and physiological implications.

    PubMed

    Gautam, Mamta; Shen, Yue; Thirkill, Twanda L; Douglas, Gordon C; Barakat, Abdul I

    2006-12-01

    Although activation of outward rectifying Cl(-) channels is one of the fastest responses of endothelial cells (ECs) to shear stress, little is known about these channels. In this study, we used whole-cell patch clamp recordings to characterize the flow-activated Cl(-) current in bovine aortic ECs (BAECs). Application of shear stress induced rapid development of a Cl(-) current that was effectively blocked by the Cl(-) channel antagonist 5-nitro-2-(3-phenopropylamino)benzoic acid (100 microM). The current initiated at a shear stress as low as 0.3 dyne/cm(2), attained its peak within minutes of flow onset, and saturated above 3.5 dynes/cm(2) approximately 2.5-3.5-fold increase over pre-flow levels). The Cl(-) current desensitized slowly in response to sustained flow, and step increases in shear stress elicited increased current only if the shear stress levels were below the 3.5 dynes/cm(2) saturation level. Oscillatory flow with a physiological oscillation frequency of 1 Hz, as occurs in disturbed flow zones prone to atherosclerosis, failed to elicit the Cl(-) current, whereas lower oscillation frequencies led to partial recovery of the current. Nonreversing pulsatile flow, generally considered protective of atherosclerosis, was as effective in eliciting the current as steady flow. Measurements using fluids of different viscosities indicated that the Cl(-) current is responsive to shear stress rather than shear rate. Blocking the flow-activated Cl(-) current abolished flow-induced Akt phosphorylation in BAECs, whereas blocking flow-sensitive K(+) currents had no effect, suggesting that flow-activated Cl(-) channels play an important role in regulating EC flow signaling.

  14. PEG-albumin supraplasma expansion is due to increased vessel wall shear stress induced by blood viscosity shear thinning.

    PubMed

    Sriram, Krishna; Tsai, Amy G; Cabrales, Pedro; Meng, Fantao; Acharya, Seetharama A; Tartakovsky, Daniel M; Intaglietta, Marcos

    2012-06-15

    We studied the extreme hemodilution to a hematocrit of 11% induced by three plasma expanders: polyethylene glycol (PEG)-conjugated albumin (PEG-Alb), 6% 70-kDa dextran, and 6% 500-kDa dextran. The experimental component of our study relied on microelectrodes and cardiac output to measure both the rheological properties of plasma-expander blood mixtures and nitric oxide (NO) bioavailability in vessel walls. The modeling component consisted of an analysis of the distribution of wall shear stress (WSS) in the microvessels. Our experiments demonstrated that plasma expansion with PEG-Alb caused a state of supraperfusion with cardiac output 40% above baseline, significantly increased NO vessel wall bioavailability, and lowered peripheral vascular resistance. We attributed this behavior to the shear thinning nature of blood and PEG-Alb mixtures. To substantiate this hypothesis, we developed a mathematical model of non-Newtonian blood flow in a vessel. Our model used the Quemada rheological constitutive relationship to express blood viscosity in terms of both hematocrit and shear rate. The model revealed that the net effect of the hemodilution induced by relatively low-viscosity shear thinning PEG-Alb plasma expanders is to reduce overall blood viscosity and to increase the WSS, thus intensifying endothelial NO production. These changes act synergistically, significantly increasing cardiac output and perfusion due to lowered overall peripheral vascular resistance.

  15. Design and Validation of a Novel Bioreactor to Subject Aortic Valve Leaflets to Side-Specific Shear Stress

    PubMed Central

    Sun, Ling; Rajamannan, Nalini M.; Sucosky, Philippe

    2014-01-01

    Hemodynamic stresses are presumed to play an important role in the development of calcific aortic valve disease (CAVD). The elucidation of the shear stress mechanisms involved in the pathogenesis of CAVD has been hampered by the complexity of the native unsteady and side-specific valvular flow environment. To address this gap, this article describes the design and validation of a novel device to expose leaflet samples to time-dependent side-specific shear stress. The device built on a double cone-and-plate geometry was dimensioned based on our previous single-sided shear stress device that minimizes secondary flow effects inherent to this geometry. A fluid–structure interaction (FSI) model was designed to predict the actual shear stress produced on a tissue sample mounted in the new device. Staining was performed on porcine leaflets conditioned in the new bioreactor to assess endothelial integrity and cellular apoptosis. The FSI results demonstrated good agreement between the target (native) and the actual side-specific shear stress produced on a tissue sample. No significant difference in endothelial integrity and cellular apoptosis was detected between samples conditioned for 96 h and fresh controls. This new device will enable the investigation of valvular response to normal and pathologic hemodynamics and the potential mechano-etiology of CAVD. PMID:21455792

  16. Measurement of surface shear stress vector distribution using shear-sensitive liquid crystal coatings

    NASA Astrophysics Data System (ADS)

    Zhao, Ji-Song; Scholz, Peter; Gu, Liang-Xian

    2012-10-01

    The global wall shear stress measurement technique using shear-sensitive liquid crystal (SSLC) is extended to wind tunnel measurements. Simple and common everyday equipment is used in the measurement; in particular a tungsten-halogen light bulb provides illumination and a saturation of SSLC coating color change with time is found. Spatial wall shear stress distributions of several typical flows are obtained using this technique, including wall-jet flow, vortex flow generated by a delta wing and junction flow behind a thin cylinder, although the magnitudes are not fully calibrated. The results demonstrate that SSLC technique can be extended to wind tunnel measurements with no complicated facilities used.

  17. Determination of the Shear Stress Distribution in a Laminate from the Applied Shear Resultant--A Simplified Shear Solution

    NASA Technical Reports Server (NTRS)

    Bednarcyk, Brett A.; Aboudi, Jacob; Yarrington, Phillip W.

    2007-01-01

    The simplified shear solution method is presented for approximating the through-thickness shear stress distribution within a composite laminate based on laminated beam theory. The method does not consider the solution of a particular boundary value problem, rather it requires only knowledge of the global shear loading, geometry, and material properties of the laminate or panel. It is thus analogous to lamination theory in that ply level stresses can be efficiently determined from global load resultants (as determined, for instance, by finite element analysis) at a given location in a structure and used to evaluate the margin of safety on a ply by ply basis. The simplified shear solution stress distribution is zero at free surfaces, continuous at ply boundaries, and integrates to the applied shear load. Comparisons to existing theories are made for a variety of laminates, and design examples are provided illustrating the use of the method for determining through-thickness shear stress margins in several types of composite panels and in the context of a finite element structural analysis.

  18. Shear-stress sensitive lenticular vesicles for targeted drug delivery.

    PubMed

    Holme, Margaret N; Fedotenko, Illya A; Abegg, Daniel; Althaus, Jasmin; Babel, Lucille; Favarger, France; Reiter, Renate; Tanasescu, Radu; Zaffalon, Pierre-Léonard; Ziegler, André; Müller, Bert; Saxer, Till; Zumbuehl, Andreas

    2012-08-01

    Atherosclerosis results in the narrowing of arterial blood vessels and this causes significant changes in the endogenous shear stress between healthy and constricted arteries. Nanocontainers that can release drugs locally with such rheological changes can be very useful. Here, we show that vesicles made from an artificial 1,3-diaminophospholipid are stable under static conditions but release their contents at elevated shear stress. These vesicles have a lenticular morphology, which potentially leads to instabilities along their equator. Using a model cardiovascular system based on polymer tubes and an external pump to represent shear stress in healthy and constricted vessels of the heart, we show that drugs preferentially release from the vesicles in constricted vessels that have high shear stress.

  19. Production of functional proteins: balance of shear stress and gravity

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas John (Inventor); Hammond, Timothy Grant (Inventor); Kaysen, James Howard (Inventor)

    2007-01-01

    The present invention provides a method for production of functional proteins including hormones by renal cells in a three dimensional co-culture process responsive to shear stress using a rotating wall vessel. Natural mixture of renal cells expresses the enzyme 1-a-hydroxylase which can be used to generate the active form of vitamin D: 1,25-diOH vitamin D3. The fibroblast cultures and co-culture of renal cortical cells express the gene for erythropoietin and secrete erythropoietin into the culture supernatant. Other shear stress response genes are also modulated by shear stress, such as toxin receptors megalin and cubulin (gp280). Also provided is a method of treating in-need individual with the functional proteins produced in a three dimensional co-culture process responsive to shear stress using a rotating wall vessel.

  20. Production of functional proteins: balance of shear stress and gravity

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas John (Inventor); Hammond, Timothy Grant (Inventor); Kaysen, James Howard (Inventor)

    2004-01-01

    The present invention provides a method for production of functional proteins including hormones by renal cells in a three dimensional co-culture process responsive to shear stress using a rotating wall vessel. Natural mixture of renal cells expresses the enzyme 1-a-hydroxylase which can be used to generate the active form of vitamin D: 1,25-diOH vitamin D3. The fibroblast cultures and co-culture of renal cortical cells express the gene for erythropoietin and secrete erythropoietin into the culture supernatant. Other shear stress response genes are also modulated by shear stress, such as toxin receptors megalin and cubulin (gp280). Also provided is a method of treating in-need individual with the functional proteins produced in a three dimensional co-culture process responsive to shear stress using a rotating wall vessel.

  1. Production of functional proteins: balance of shear stress and gravity

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas John (Inventor); Hammond, Timothy Grant (Inventor); Kaysen, James Howard (Inventor)

    2011-01-01

    A method for the production of functional proteins including hormones by renal cells in a three dimensional culturing process responsive to shear stress uses a rotating wall vessel. Natural mixture of renal cells expresses the enzyme 1-.alpha.-hydroxylase which can be used to generate the active form of vitamin D: 1,25-diOH vitamin D.sub.3. The fibroblast cultures and co-culture of renal cortical cells express the gene for erythropoietin and secrete erythropoietin into the culture supernatant. Other shear stress response genes are also modulated by shear stress, such as toxin receptors megalin and cubulin (gp280). Also provided is a method of treating an in-need individual with the functional proteins produced in a three dimensional co-culture process responsive to shear stress using a rotating wall vessel.

  2. Vorticity alignment and negative normal stresses in sheared attractive emulsions.

    PubMed

    Montesi, Alberto; Peña, Alejandro A; Pasquali, Matteo

    2004-02-06

    Attractive emulsions near the colloidal glass transition are investigated by rheometry and optical microscopy under shear. We find that (i) the apparent viscosity eta drops with increasing shear rate, then remains approximately constant in a range of shear rates, then continues to decay; (ii) the first normal stress difference N1 transitions sharply from nearly zero to negative in the region of constant shear viscosity; and (iii) correspondingly, cylindrical flocs form, align along the vorticity, and undergo a log-rolling movement. An analysis of the interplay between steric constraints, attractive forces, and composition explains this behavior, which seems universal to several other complex systems.

  3. Effect of fluid shear stress on portal vein remodeling in a rat model of portal hypertension.

    PubMed

    Wen, Bin; Liang, Jian; Deng, Xin; Chen, Ran; Peng, Peichun

    2015-01-01

    Aims. To explore the effects and mechanisms of fluid shear stress on portal vein remodeling in a rat model of portal hypertension. Methods. Subcutaneous injections of CCl4 were given to establish a rat model of liver cirrhosis and portal hypertension. Biomechanical technology was adopted to determine the dynamic changes of haemodynamic indices and fluid shear stress. Nitric oxide (NO), synthase (NOS), and endothelin-1 (ET-1) of the portal vein blood were measured. Changes in geometric structure and ultrastructure of the portal vein were observed using optical and electron microscopy. Results. After the CC14 injections, rat haemodynamics were notably altered. From week 4 onwards, PVP, PVF, and PVR gradually and significantly increased (P < 0.05 versus baseline). The fluid shear stress declined from week 4 onwards (P < 0.01 versus control group). NO, NOS, and ET-1 increased after repeated CCI4 injections. Hematoxylin and eosin staining showed thickened portal vein walls, with increased inside and outside diameters. Electron microscopy revealed different degrees of endothelial cell degeneration, destruction of basement membrane integrity, proliferating, and hypertrophic smooth muscle cells. Conclusions. Fluid shear stress not only influenced the biomechanical environment of the portal vein but also participated in vascular remodeling.

  4. Investigation of platelet margination phenomena at elevated shear stress.

    PubMed

    Zhao, Rui; Kameneva, Marina V; Antaki, James F

    2007-01-01

    Thrombosis is a common complication following the surgical implantation of blood contacting artificial organs. Platelet transport, which is an important process of thrombosis and strongly modulated by flow dynamics, has not been investigated under the shear stress level associated with these devices, which may range from tens to several hundred Pascal.The current research investigated platelet transport within blood under supra-physiological shear stress conditions through a micro flow visualization approach. Images of platelet-sized fluorescent particles in the blood flow were recorded within microchannels (2 cm x 100 microm x 100 microm). The results successfully demonstrated the occurrence of platelet-sized particle margination under shear stresses up to 193 Pa, revealing a platelet near-wall excess up to 8.7 near the wall (within 15 microm) at the highest shear stress. The concentration of red blood cells was found to influence the stream-wise development of platelet margination which was clearly observed in the 20% Ht sample but not the 40% Ht sample. Shear stress had a less dramatic effect on the margination phenomenon than did hematocrit. The results imply that cell-cell collision is an important factor for platelet transport under supra-physiologic shear stress conditions. It is anticipated that these results will contribute to the future design and optimization of artificial organs.

  5. Cell adhesion on zein films under shear stress field.

    PubMed

    Han, Yi-Long; Xu, Qin; Lu, Zhiqian; Wang, Jin-Ye

    2013-11-01

    Vascular implants after implantation need to improve the ability of cells to withstand flow-shear stress. As such, we want to test whether zein films could improve the flow-shear stress resistance of cells by control of their surface morphology. We chose Collagen, poly L-lactic acid (PLLA) and three types of zein as the coating films and evaluated the flow-shear stress resistance of NIH3T3, and EA.hy926 on these respective films. The results showed that the retention of two cell lines on Collagen film was better than PLLA and zein films. The cell retention of EA.hy926 on Zein 3 film with higher roughness was better than Zein 1 film with a flat surface in the first 2h. The cell retention of NIH3T3 on a rougher surface was always better than the smoother one under flow-shear stress condition for 6h. Observation of cell morphologies showed that the aspect ratio changed significantly for NIH3T3 cells upon flow-shear stress condition, as shown by reduced numbers of pseudopodia, increased cell rounding and shrinkage. Zein 3 film with higher roughness improved the flow-shear stress resistance of cells and might be used in vascular implant coatings.

  6. Surface micromachined differential piezoelectric shear-stress sensors

    NASA Astrophysics Data System (ADS)

    Williams, Randall P.; Kim, Donghwan; Gawalt, David P.; Hall, Neal A.

    2017-01-01

    The ability to measure viscous wall shear stress in high-speed flows is important for verifying simulated results typically obtained from direct numerical simulation in the aerodynamics research community, and robust sensors are required to measure wall shear reliably under such high-speed conditions. This letter summarizes the design, fabrication, and testing of a surface micromachined piezoelectric shear-stress sensor which uses a thin piezoelectric film to generate a voltage proportional to an applied shear stress without additional moving parts. A differential-cell architecture is used to enhance selectivity to shear stress while canceling normal-stress sensitivity. The conceptual design, fabrication details, and experimental measurements of device sensitivity are presented. A finite element model is used to validate the device performance against measurements, and to provide insight into the potential and electric fields underlying the device concept. The potential for understanding device behavior and optimization through modeling is illustrated using finite element analysis results. The minimum detectable shear stress for the sensor is estimated to be 52.9 mPa  √Hz-1 at 1.5 kHz.

  7. Effects of Fluid Shear Stress on Cancer Stem Cell Viability

    NASA Astrophysics Data System (ADS)

    Sunday, Brittney; Triantafillu, Ursula; Domier, Ria; Kim, Yonghyun

    2014-11-01

    Cancer stem cells (CSCs), which are believed to be the source of tumor formation, are exposed to fluid shear stress as a result of blood flow within the blood vessels. It was theorized that CSCs would be less susceptible to cell death than non-CSCs after both types of cell were exposed to a fluid shear stress, and that higher levels of fluid shear stress would result in lower levels of cell viability for both cell types. To test this hypothesis, U87 glioblastoma cells were cultured adherently (containing smaller populations of CSCs) and spherically (containing larger populations of CSCs). They were exposed to fluid shear stress in a simulated blood flow through a 125-micrometer diameter polyetheretherketone (PEEK) tubing using a syringe pump. After exposure, cell viability data was collected using a BioRad TC20 Automated Cell Counter. Each cell type was tested at three physiological shear stress values: 5, 20, and 60 dynes per centimeter squared. In general, it was found that the CSC-enriched U87 sphere cells had higher cell viability than the CSC-depleted U87 adherent cancer cells. Interestingly, it was also observed that the cell viability was not negatively affected by the higher fluid shear stress values in the tested range. In future follow-up studies, higher shear stresses will be tested. Furthermore, CSCs from different tumor origins (e.g. breast tumor, prostate tumor) will be tested to determine cell-specific shear sensitivity. National Science Foundation Grant #1358991 supported the first author as an REU student.

  8. Shear- vs. nanotopography-guided control of growth of endothelial cells on RGD-nanoparticle-nanowell arrays

    PubMed Central

    2013-01-01

    Endothelialization of therapeutic cardiovascular implants is essential for their intravascular hemocompatibility. We previously described a novel nanowell-RGD-nanoparticle ensemble, which when applied to surfaces led to enhanced endothelialization and retention under static conditions and low flow rates. In the present study we extend our work to determine the interrelated effects of flow rate and the orientation of ensemble-decorated surface arrays on the growth, adhesion and morphology of endothelial cells. Human umbilical vascular endothelial cells (HUVECs) were grown on array surfaces with either 1 μm × 5 μm spacing (“parallel to flow”) and 5 μm × 1 μm spacing (“perpendicular to flow”) and were exposed to a range of shear stress of (0 to 4.7 ± 0.2 dyn·cm-2 ), utilizing a pulsatile flow chamber. Under physiological flow (4.7 ± 0.2 dyn·cm-2), RGD-nanoparticle-nanowell array patterning significantly enhanced cell adhesion and spreading compared with control surfaces and with static conditions. Furthermore, improved adhesion coincided with higher alignment to surface patterning, intimating the importance of interaction and response to the array surface as a means of resisting flow detachment. Under sub-physiological condition (1.7 ± 0.3 dyn·cm-2; corresponding to early angiogenesis), nanowell-nanoparticle patterning did not provide enhanced cell growth and adhesion compared with control surfaces. However, it revealed increased alignment along the direction of flow, rather than the direction of the pattern, thus potentially indicating a threshold for cell guidance and related retention. These results could provide a cue for controlling cell growth and alignment under varying physiological conditions. PMID:23607894

  9. Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein kinase A-dependent mechanism

    NASA Technical Reports Server (NTRS)

    Boo, Yong Chool; Hwang, Jinah; Sykes, Michelle; Michell, Belinda J.; Kemp, Bruce E.; Lum, Hazel; Jo, Hanjoong

    2002-01-01

    Shear stress stimulates nitric oxide (NO) production by phosphorylating endothelial NO synthase (eNOS) at Ser(1179) in a phosphoinositide-3-kinase (PI3K)- and protein kinase A (PKA)-dependent manner. The eNOS has additional potential phosphorylation sites, including Ser(116), Thr(497), and Ser(635). Here, we studied these potential phosphorylation sites in response to shear, vascular endothelial growth factor (VEGF), and 8-bromocAMP (8-BRcAMP) in bovine aortic endothelial cells (BAEC). All three stimuli induced phosphorylation of eNOS at Ser(635), which was consistently slower than that at Ser(1179). Thr(497) was rapidly dephosphorylated by 8-BRcAMP but not by shear and VEGF. None of the stimuli phosphorylated Ser(116). Whereas shear-stimulated Ser(635) phosphorylation was not affected by phosphoinositide-3-kinase inhibitors wortmannin and LY-294002, it was blocked by either treating the cells with a PKA inhibitor H89 or infecting them with a recombinant adenovirus-expressing PKA inhibitor. These results suggest that shear stress stimulates eNOS by two different mechanisms: 1) PKA- and PI3K-dependent and 2) PKA-dependent but PI3K-independent pathways. Phosphorylation of Ser(635) may play an important role in chronic regulation of eNOS in response to mechanical and humoral stimuli.

  10. Effects of Exercise Intensity on Postexercise Endothelial Function and Oxidative Stress

    PubMed Central

    McClean, Conor; Harris, Ryan A.; Brown, Malcolm; Brown, John C.; Davison, Gareth W.

    2015-01-01

    Purpose. To measure endothelial function and oxidative stress immediately, 90 minutes, and three hours after exercise of varying intensities. Methods. Sixteen apparently healthy men completed three exercise bouts of treadmill running for 30 minutes at 55% V˙O2max (mild); 20 minutes at 75% V˙O2max (moderate); or 5 minutes at 100% V˙O2max (maximal) in random order. Brachial artery flow-mediated dilation (FMD) was assessed with venous blood samples drawn for measurement of endothelin-1 (ET-1), lipid hydroperoxides (LOOHs), and lipid soluble antioxidants. Results. LOOH increased immediately following moderate exercise (P < 0.05). ET-1 was higher immediately after exercise and 3 hours after exercise in the mild trial compared to maximal one (P < 0.05). Transient decreases were detected for ΔFMD/ShearAUC from baseline following maximal exercise, but it normalised at 3 hours after exercise (P < 0.05). Shear rate was higher immediately after exercise in the maximal trial compared to mild exercise (P < 0.05). No changes in baseline diameter, peak diameter, absolute change in diameter, or FMD were observed following any of the exercise trials (P > 0.05). Conclusions. Acute exercise at different intensities elicits varied effects on oxidative stress, shear rate, and ET-1 that do not appear to mediate changes in endothelial function measured by FMD. PMID:26583061

  11. Prediction of plantar shear stress distribution by artificial intelligence methods.

    PubMed

    Yavuz, Metin; Ocak, Hasan; Hetherington, Vincent J; Davis, Brian L

    2009-09-01

    Shear forces under the human foot are thought to be responsible for various foot pathologies such as diabetic plantar ulcers and athletic blisters. Frictional shear forces might also play a role in the metatarsalgia observed among hallux valgus (HaV) and rheumatoid arthritis (RA) patients. Due to the absence of commercial devices capable of measuring shear stress distribution, a number of linear models were developed. All of these have met with limited success. This study used nonlinear methods, specifically neural network and fuzzy logic schemes, to predict the distribution of plantar shear forces based on vertical loading parameters. In total, 73 subjects were recruited; 17 had diabetic neuropathy, 14 had HaV, 9 had RA, 11 had frequent foot blisters, and 22 were healthy. A feed-forward neural network (NN) and adaptive neurofuzzy inference system (NFIS) were built. These systems were then applied to a custom-built platform, which collected plantar pressure and shear stress data as subjects walked over the device. The inputs to both models were peak pressure, peak pressure-time integral, and time to peak pressure, and the output was peak resultant shear. Root-mean-square error (RMSE) values were calculated to test the models' accuracy. RMSE/actual shear ratio varied between 0.27 and 0.40 for NN predictions. Similarly, NFIS estimations resulted in a 0.28-0.37 ratio for local peak values in all subject groups. On the other hand, error percentages for global peak shear values were found to be in the range 11.4-44.1. These results indicate that there is no direct relationship between pressure and shear magnitudes. Future research should aim to decrease error levels by introducing shear stress dependent variables into the models.

  12. Elevated Shear Stress in Arteriovenous Fistulae: Is There Mechanical Homeostasis?

    NASA Astrophysics Data System (ADS)

    McGah, Patrick; Leotta, Daniel; Beach, Kirk; Aliseda, Alberto

    2011-11-01

    Arteriovenous fistulae are created surgically to provide access for dialysis in patients with renal failure. The current hypothesis is that the rapid remodeling occurring after the fistula creation is in part a process to restore the mechanical stresses to some preferred level (i.e. mechanical homeostasis). Given that nearly 50% of fistulae require an intervention after one year, understanding the altered hemodynamic stress is important in improving clinical outcomes. We perform numerical simulations of four patient-specific models of functioning fistulae reconstructed from 3D Doppler ultrasound scans. Our results show that the vessels are subjected to `normal' shear stresses away from the anastomosis; about 1 Pa in the veins and about 2.5 Pa in the arteries. However, simulations show that part of the anastomoses are consistently subjected to very high shear stress (>10Pa) over the cardiac cycle. These elevated values shear stresses are caused by the transitional flows at the anastomoses including flow separation and quasiperiodic vortex shedding. This suggests that the remodeling process lowers shear stress in the fistula but that it is limited as evidenced by the elevated shear at the anastomoses. This constant insult on the arterialized venous wall may explain the process of late fistula failure in which the dialysis access become occluded after years of use. Supported by an R21 Grant from NIDDK (DK081823).

  13. Short exposure time sensitivity of white cells to shear stress.

    PubMed

    Carter, Janell; Hristova, Katia; Harasaki, Hiroaki; Smith, W A

    2003-01-01

    White cells are a critical functional element circulating in blood. This study sheared fresh whole bovine blood in stainless steel and polymeric capillary tubes of various lengths and diameters. Flow rate was constant, resulting in a range of exposure times and shear stresses. White cell count, cell integrity (trypan blue exclusion), and phagocytic index (latex bead ingestion) were assayed. It was found that cell function declined at lower stresses than cell count. White cell count was maintained at higher stress levels at the short exposure times used here compared with the published results at longer times. This study suggests that function, not count, is the critical parameter when studying shear effects on white cells, and that, like red cells, there may be an exposure time effect and that white cell function is impacted at stresses lower than are required for hemolysis.

  14. Fluid shear stress differentially modulates expression of genes encoding basic fibroblast growth factor and platelet-derived growth factor B chain in vascular endothelium.

    PubMed Central

    Malek, A M; Gibbons, G H; Dzau, V J; Izumo, S

    1993-01-01

    Fluid shear stress has been shown to be an important regulator of vascular structure and function through its effect on the endothelial cell. We have explored the effect of shear stress on the expression of the heparin-binding growth factors platelet-derived growth factor B chain (PDGF-B) and basic fibroblast growth factor (bFGF) in bovine aortic endothelial cells using a purpose-built cone-plate viscometer. Using morphometric analysis, we have mimicked the endothelial cell shape changes encountered in vivo in response to shear stress and correlated these with changes in gene expression. Steady laminar shear stress of 15 and 36 dyn/cm2 both resulted in endothelial cell shape change, but the higher shear stress induced greater and more uniform alignment in the direction of flow and nuclear protrusion after 24 h. Steady laminar shear stress of both 15 and 36 dyn/cm2 induced a significant 3.9- and 4.2-fold decrease, respectively, in PDGF-B mRNA at 9 h. In contrast, steady laminar shear of 15 dyn/cm2 induced a mild and transient 1.5-fold increase in bFGF mRNA while shear of 36 dyn/cm2 induced a significant 4.8-fold increase at 6 h of shear which remained at 2.9-fold at 9 h. Pulsatile and turbulent shear stress showed the same effect as steady laminar shear stress (all at 15 dyn/cm2 time-average magnitude) on PDGF-B and bFGF mRNA content. Cyclic stretch (20% strain, 20/min) of cells grown on silicone substrate did not significantly affect either PDGF-B or bFGF mRNA levels. These results suggest that expression of each peptide growth factor gene is differentially regulated by fluid shear stress in the vascular endothelial cell. These results may have implications on vascular structure and function in response to hemodynamic forces and present a model for the study of transduction of mechanical stimuli into altered gene expression. Images PMID:8408655

  15. Laminar shear stress stimulates vascular smooth muscle cell apoptosis via the Akt pathway.

    PubMed

    Fitzgerald, Tamara N; Shepherd, Benjamin R; Asada, Hidenori; Teso, Desarom; Muto, Akihito; Fancher, Tiffany; Pimiento, Jose M; Maloney, Stephen P; Dardik, Alan

    2008-08-01

    Vascular smooth muscle cells (SMC) may be directly exposed to blood flow after an endothelial-denuding injury. It is not known whether direct exposure of SMC to shear stress reduces SMC turnover and contributes to the low rate of restenosis after most vascular interventions. This study examines if laminar shear stress inhibits SMC proliferation or stimulates apoptosis. Bovine aortic SMC were exposed to arterial magnitudes of laminar shear stress (11 dynes/cm(2)) for up to 24 h and compared to control SMC (0 dynes/cm(2)). SMC density was assessed by cell counting, DNA synthesis by (3)[H]-thymidine incorporation, and apoptosis by TUNEL staining. Akt, caspase, bax, and bcl-2 phosphorylation were assessed by Western blotting; caspase activity was also measured with an in vitro assay. Analysis of variance was used to compare groups. SMC exposed to laminar shear stress had a 38% decrease in cell number (n = 4, P = 0.03), 54% reduction in (3)[H]-thymidine incorporation (n = 3, P = 0.003), and 15-fold increase in TUNEL staining (n = 4, P < 0.0001). Akt phosphorylation was reduced by 67% (n = 3, P < 0.0001), whereas bax/bcl-2 phosphorylation was increased by 1.8-fold (n = 3, P = 0.01). Caspase-3 activity was increased threefold (n = 5, P = 0.03). Pretreatment of cells with ZVAD-fmk or wortmannin resulted in 42% increased cell retention (n = 3, P < 0.01) and a fourfold increase in apoptosis (n = 3, P < 0.04), respectively. Cells transduced with constitutively-active Akt had twofold decreased apoptosis (n = 3, P < 0.002). SMC exposed to laminar shear stress have decreased proliferation and increased apoptosis, mediated by the Akt pathway. These results suggest that augmentation of SMC apoptosis may be an alternative strategy to inhibit restenosis after vascular injury.

  16. On the gating of mechanosensitive channels by fluid shear stress

    NASA Astrophysics Data System (ADS)

    Peng, Zhangli; Pak, On Shun; Feng, Zhe; Liu, Allen P.; Young, Yuan-Nan

    2016-12-01

    Mechanosensation is an important process in biological fluid-structure interaction. To understand the biophysics underlying mechanosensation, it is essential to quantify the correlation between membrane deformation, membrane tension, external fluid shear stress, and conformation of mechanosensitive (MS) channels. Smoothed dissipative particle dynamics (SDPD) simulations of vesicle/cell in three types of flow configurations are conducted to calculate the tension in lipid membrane due to fluid shear stress from the surrounding viscous flow. In combination with a simple continuum model for an MS channel, SDPD simulation results suggest that shearing adhered vesicles/cells is more effective to induce membrane tension sufficient to stretch MS channels open than a free shear flow or a constrictive channel flow. In addition, we incorporate the bilayer-cytoskeletal interaction in a two-component model to probe the effects of a cytoskeletal network on the gating of MS channels.

  17. Shear Stress Sensing with Elastic Microfence Structures

    NASA Technical Reports Server (NTRS)

    Cisotto, Alexxandra; Palmieri, Frank L.; Saini, Aditya; Lin, Yi; Thurman, Christopher S; Kim, Jinwook; Kim, Taeyang; Connell, John W.; Zhu, Yong; Gopalarathnam, Ashok; Jiang, Xiaoning; Wohl, Christopher J.

    2015-01-01

    In this work, elastic microfences were generated for the purpose of measuring shear forces acting on a wind tunnel model. The microfences were fabricated in a two part process involving laser ablation patterning to generate a template in a polymer film followed by soft lithography with a two-part silicone. Incorporation of a fluorescent dye was demonstrated as a method to enhance contrast between the sensing elements and the substrate. Sensing elements consisted of multiple microfences prepared at different orientations to enable determination of both shear force and directionality. Microfence arrays were integrated into an optical microscope with sub-micrometer resolution. Initial experiments were conducted on a flat plate wind tunnel model. Both image stabilization algorithms and digital image correlation were utilized to determine the amount of fence deflection as a result of airflow. Initial free jet experiments indicated that the microfences could be readily displaced and this displacement was recorded through the microscope.

  18. Dynamic wall shear stress measurements in a turbulent channel flow

    NASA Astrophysics Data System (ADS)

    Amili, Omid; Soria, Julio

    2010-11-01

    To quantify and understand the dynamics of near wall momentum transfer, high spatial resolution, time-resolved measurements of wall shear stress distribution are essential. In this study, a film-based shear stress sensor has been used to measure the time-resolved local wall shear stress distribution in a turbulent channel flow. Measurements have been undertaken in a turbulent channel flow at Reynolds numbers up to 130,000 based on the bulk velocity and channel height. The measured fluctuating wall shear stress distribution provides spatio-temporal information of the characteristics of near wall structures by detecting their footprints. The span-wise extent of the positive two-point correlation of the stream-wise shear stress fluctuations provides the average width in the order of 100 wall units for the near-wall coherent structures. An investigation of the topological features of the velocity gradient and rate of strain tensors enables us to show an intrinsic characteristic of the near wall flow, which follows a two-dimensional flow pattern.

  19. Molecular origins of higher harmonics in large-amplitude oscillatory shear flow: Shear stress response

    NASA Astrophysics Data System (ADS)

    Gilbert, P. H.; Giacomin, A. J.

    2016-10-01

    Recent work has focused on deepening our understanding of the molecular origins of the higher harmonics that arise in the shear stress response of polymeric liquids in large-amplitude oscillatory shear flow. For instance, these higher harmonics have been explained by just considering the orientation distribution of rigid dumbbells suspended in a Newtonian solvent. These dumbbells, when in dilute suspension, form the simplest relevant molecular model of polymer viscoelasticity, and this model specifically neglects interactions between the polymer molecules [R. B. Bird et al., "Dilute rigid dumbbell suspensions in large-amplitude oscillatory shear flow: Shear stress response," J. Chem. Phys. 140, 074904 (2014)]. In this paper, we explore these interactions by examining the Curtiss-Bird model, a kinetic molecular theory designed specifically to account for the restricted motions that arise when polymer chains are concentrated, thus interacting and specifically, entangled. We begin our comparison using a heretofore ignored explicit analytical solution [X.-J. Fan and R. B. Bird, "A kinetic theory for polymer melts. VI. Calculation of additional material functions," J. Non-Newtonian Fluid Mech. 15, 341 (1984)]. For concentrated systems, the chain motion transverse to the chain axis is more restricted than along the axis. This anisotropy is described by the link tension coefficient, ɛ, for which several special cases arise: ɛ = 0 corresponds to reptation, ɛ > 1/8 to rod-climbing, 1/5 ≤ ɛ ≤ 3/4 to reasonable predictions for shear-thinning in steady simple shear flow, and ɛ = 1 to the dilute solution without hydrodynamic interaction. In this paper, we examine the shapes of the shear stress versus shear rate loops for the special cases ɛ = (" separators=" 0 , 1 / 8 , 3 / 8 , 1 ) , and we compare these with those of rigid dumbbell and reptation model predictions.

  20. Targeted Delivery of Shear Stress-Inducible Micrornas by Nanoparticles to Prevent Vulnerable Atherosclerotic Lesions

    PubMed Central

    Wong, Wing Tak; Ma, Shuangtao; Tian, Xiao Yu; Gonzalez, Andrea Banuet; Ebong, Eno E.; Shen, Haifa

    2016-01-01

    Atherosclerosis is a chronic inflammatory vascular wall disease, and endothelial cell dysfunction plays an important role in its development and progression. Under the influence of laminar shear stress, however, the endothelium releases homeostatic factors such as nitric oxide and expresses of vasoprotective microRNAs that are resistant to atherosclerosis. Adhesion molecules such as E-selectin, exhibited on the endothelial surface, recruit monocytes that enter the vessel wall to form foam cells. Accumulation of these foam cells form fatty streaks that may progress to atherosclerotic plaques in the blood vessel wall. Interestingly, E-selectin may also serve as an affinity moiety for targeted drug delivery against atherosclerosis. We have recently developed an E-selectin-targeted platform that enriches therapeutic microRNAs in the inflamed endothelium to inhibit formation of vulnerable atherosclerotic plaques. PMID:27826369

  1. A Multichannel Dampened Flow System for Studies on Shear Stress-Mediated Mechanotransduction

    PubMed Central

    Voyvodic, Peter L.; Min, Daniel; Baker, Aaron B.

    2012-01-01

    Shear stresses are powerful regulators of cellular function and potent mediators of the development of vascular disease. We have designed and optimized a system allowing the application of flow to cultured cells in a multichannel format. By using a multichannel peristaltic pump, flow can be driven continuously in the system for long-term studies in multiple isolated flow loops. A key component of the system is a dual-chamber pulse dampener that removes the pulsatility of the flow without the need for having an open system or elevated reservoir. We optimized the design parameters of the pulse dampening chambers for the maximum reduction in flow pulsation while minimizing the fluid needed for each isolated flow channel. Human umbilical vein endothelial cells (HUVECs) were exposed to steady and pulsatile shear stress using the system. We found that cells under steady flow had a marked increased production of eNOS and formation of actin stress fibers in comparison to those under pulsatile flow conditions. Overall, the results confirm the utility of the device as a practical means to apply shear stress to cultured cells in the multichannel format and provide steady, long term flow to microfluidic devices. PMID:22836694

  2. Shear-stress-controlled dynamics of nematic complex fluids.

    PubMed

    Klapp, Sabine H L; Hess, Siegfried

    2010-05-01

    Based on a mesoscopic theory we investigate the nonequilibrium dynamics of a sheared nematic liquid, with the control parameter being the shear stress σ xy (rather than the usual shear rate, γ). To this end we supplement the equations of motion for the orientational order parameters by an equation for γ, which then becomes time dependent. Shearing the system from an isotropic state, the stress-controlled flow properties turn out to be essentially identical to those at fixed γ. Pronounced differences occur when the equilibrium state is nematic. Here, shearing at controlled γ yields several nonequilibrium transitions between different dynamic states, including chaotic regimes. The corresponding stress-controlled system has only one transition from a regular periodic into a stationary (shear-aligned) state. The position of this transition in the σ xy-γ plane turns out to be tunable by the delay time entering our control scheme for σ xy. Moreover, a sudden change in the control method can stabilize the chaotic states appearing at fixed γ.

  3. Stress-Induced Premature Senescence of Endothelial and Endothelial Progenitor Cells

    PubMed Central

    Goligorsky, M.S.; Hirschi, K.

    2016-01-01

    This brief overview of premature senescence of dysfunctional endothelial and endothelial progenitor cells provides information on endothelial cell differentiation and specialization, their ontogeny, and controversies related to endothelial stem and progenitor cells. Stressors responsible for the dysfunction of endothelial and endothelial progenitor cells, as well as cellular mechanisms and consequences of endothelial cell dysfunction are presented. Metabolic signatures of dysfunctional endothelial cells and senescence pathways are described. Emerging strategies to rejuvenate endothelial and endothelial progenitor cells conclude the review. PMID:27451101

  4. Effects of dynamic shear and transmural pressure on wall shear stress sensitivity in collecting lymphatic vessels.

    PubMed

    Kornuta, Jeffrey A; Nepiyushchikh, Zhanna; Gasheva, Olga Y; Mukherjee, Anish; Zawieja, David C; Dixon, J Brandon

    2015-11-01

    Given the known mechanosensitivity of the lymphatic vasculature, we sought to investigate the effects of dynamic wall shear stress (WSS) on collecting lymphatic vessels while controlling for transmural pressure. Using a previously developed ex vivo lymphatic perfusion system (ELPS) capable of independently controlling both transaxial pressure gradient and average transmural pressure on an isolated lymphatic vessel, we imposed a multitude of flow conditions on rat thoracic ducts, while controlling for transmural pressure and measuring diameter changes. By gradually increasing the imposed flow through a vessel, we determined the WSS at which the vessel first shows sign of contraction inhibition, defining this point as the shear stress sensitivity of the vessel. The shear stress threshold that triggered a contractile response was significantly greater at a transmural pressure of 5 cmH2O (0.97 dyne/cm(2)) than at 3 cmH2O (0.64 dyne/cm(2)). While contraction frequency was reduced when a steady WSS was applied, this inhibition was reversed when the applied WSS oscillated, even though the mean wall shear stresses between the conditions were not significantly different. When the applied oscillatory WSS was large enough, flow itself synchronized the lymphatic contractions to the exact frequency of the applied waveform. Both transmural pressure and the rate of change of WSS have significant impacts on the contractile response of lymphatic vessels to flow. Specifically, time-varying shear stress can alter the inhibition of phasic contraction frequency and even coordinate contractions, providing evidence that dynamic shear could play an important role in the contractile function of collecting lymphatic vessels.

  5. Effects of dynamic shear and transmural pressure on wall shear stress sensitivity in collecting lymphatic vessels

    PubMed Central

    Kornuta, Jeffrey A.; Nepiyushchikh, Zhanna; Gasheva, Olga Y.; Mukherjee, Anish; Zawieja, David C.

    2015-01-01

    Given the known mechanosensitivity of the lymphatic vasculature, we sought to investigate the effects of dynamic wall shear stress (WSS) on collecting lymphatic vessels while controlling for transmural pressure. Using a previously developed ex vivo lymphatic perfusion system (ELPS) capable of independently controlling both transaxial pressure gradient and average transmural pressure on an isolated lymphatic vessel, we imposed a multitude of flow conditions on rat thoracic ducts, while controlling for transmural pressure and measuring diameter changes. By gradually increasing the imposed flow through a vessel, we determined the WSS at which the vessel first shows sign of contraction inhibition, defining this point as the shear stress sensitivity of the vessel. The shear stress threshold that triggered a contractile response was significantly greater at a transmural pressure of 5 cmH2O (0.97 dyne/cm2) than at 3 cmH2O (0.64 dyne/cm2). While contraction frequency was reduced when a steady WSS was applied, this inhibition was reversed when the applied WSS oscillated, even though the mean wall shear stresses between the conditions were not significantly different. When the applied oscillatory WSS was large enough, flow itself synchronized the lymphatic contractions to the exact frequency of the applied waveform. Both transmural pressure and the rate of change of WSS have significant impacts on the contractile response of lymphatic vessels to flow. Specifically, time-varying shear stress can alter the inhibition of phasic contraction frequency and even coordinate contractions, providing evidence that dynamic shear could play an important role in the contractile function of collecting lymphatic vessels. PMID:26333787

  6. High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis

    PubMed Central

    Wang, Yi; Qiu, Juhui; Luo, Shisui; Xie, Xiang; Zheng, Yiming; Zhang, Kang; Ye, Zhiyi; Liu, Wanqian; Gregersen, Hans; Wang, Guixue

    2016-01-01

    Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic strokes. Inhibition of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular grafts. Shear stress (SS) influences the formation and development of atherosclerosis. The current review focuses on the vulnerable plaques observed in the high shear stress (HSS) regions, which localizes at the proximal region of the plaque intruding into the lumen. The vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque formation. These results greatly challenge the established belief that low shear stress is important for expansive remodelling, which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions. PMID:27482467

  7. Impact of wall shear stress and ligand avidity on binding of anti-CD146-coated nanoparticles to murine tumor endothelium under flow.

    PubMed

    Thomann, Stefan; Baek, Sunhwa; Ryschich, Eduard

    2015-11-24

    The endothelial phenotype of tumor blood vessels differs from the liver and forms an important base for endothelium-specific targeting by antibody-coated nanoparticles. Although differences of shear stress and ligand avidity can modulate the nanoparticle binding to endothelium, these mechanisms are still poorly studied. This study analyzed the binding of antibody-coated nanoparticles to tumor and liver endothelium under controlled flow conditions and verified this binding in tumor models in vivo. Binding of anti-CD146-coated nanoparticles, but not of antibody was significantly reduced under increased wall shear stress and the degree of nanoparticle binding correlated with the avidity of the coating. The intravascular wall shear stress favors nanoparticle binding at the site of higher avidity of endothelial epitope which additionally promotes the selectivity to tumor endothelium. After intravenous application in vivo, pegylated self-coated nanoparticles showed specific binding to tumor endothelium, whereas the nanoparticle binding to the liver endothelium was very low. This study provides a rationale that selective binding of mAb-coated nanoparticles to tumor endothelium is achieved by two factors: higher expression of endothelial epitope and higher nanoparticle shearing from liver endothelium. The combination of endothelial marker targeting and the use of shear stress-controlled nanoparticle capture can be used for selective intratumoral drug delivery.

  8. A Rotary Flow Channel for Shear Stress Sensor Calibration

    NASA Technical Reports Server (NTRS)

    Zuckerwar, Allan J.; Scott, Michael A.

    2004-01-01

    A proposed shear sensor calibrator consists of a rotating wheel with the sensor mounted tangential to the rim and positioned in close proximity to the rim. The shear stress generated by the flow at the sensor position is simply tau(sub omega) = (mu)r(omega)/h, where mu is the viscosity of the ambient gas, r the wheel radius, omega the angular velocity of the wheel, and h the width of the gap between the wheel rim and the sensor. With numerical values of mu = 31 (mu)Pa s (neon at room temperature), r = 0.5 m, omega = 754 /s (7200 rpm), and h = 50.8 m, a shear stress of tau(sub omega) = 231 Pa can be generated. An analysis based on one-dimensional flow, with the flow velocity having only an angular component as a function of the axial and radial coordinates, yields corrections to the above simple formula for the curvature of the wheel, flatness of the sensor, and finite width of the wheel. It is assumed that the sensor mount contains a trough (sidewalls) to render a velocity release boundary condition at the edges of the rim. The Taylor number under maximum flow conditions is found to be 62.3, sufficiently low to obviate flow instability. The fact that the parameters entering into the evaluation of the shear stress can be measured to high accuracy with well-defined uncertainties makes the proposed calibrator suitable for a physical standard for shear stress calibration.

  9. Nonlinear Reynolds stress model for turbulent shear flows

    NASA Technical Reports Server (NTRS)

    Barton, J. Michael; Rubinstein, R.; Kirtley, K. R.

    1991-01-01

    A nonlinear algebraic Reynolds stress model, derived using the renormalization group, is applied to equilibrium homogeneous shear flow and fully developed flow in a square duct. The model, which is quadratically nonlinear in the velocity gradients, successfully captures the large-scale inhomogeneity and anisotropy of the flows studied. The ratios of normal stresses, as well as the actual magnitudes of the stresses are correctly predicted for equilibrium homogeneous shear flow. Reynolds normal stress anisotropy and attendant turbulence driven secondary flow are predicted for a square duct. Profiles of mean velocity and normal stresses are in good agreement with measurements. Very close to walls, agreement with measurements diminishes. The model has the benefit of containing no arbitrary constants; all values are determined directly from the theory. It seems that near wall behavior is influenced by more than the large scale anisotropy accommodated in the current model. More accurate near wall calculations may well require a model for anisotropic dissipation.

  10. Laminar shear stress upregulates endothelial Ca²⁺-activated K⁺ channels KCa2.3 and KCa3.1 via a Ca²⁺/calmodulin-dependent protein kinase kinase/Akt/p300 cascade.

    PubMed

    Takai, Jun; Santu, Alexandra; Zheng, Haifeng; Koh, Sang Don; Ohta, Masanori; Filimban, Linda M; Lemaître, Vincent; Teraoka, Ryutaro; Jo, Hanjoong; Miura, Hiroto

    2013-08-15

    In endothelial cells (ECs), Ca²⁺-activated K⁺ channels KCa2.3 and KCa3.1 play a crucial role in the regulation of arterial tone via producing NO and endothelium-derived hyperpolarizing factors. Since a rise in intracellular Ca²⁺ levels and activation of p300 histone acetyltransferase are early EC responses to laminar shear stress (LS) for the transcriptional activation of genes, we examined the role of Ca²⁺/calmodulin-dependent kinase kinase (CaMKK), the most upstream element of a Ca²⁺/calmodulin-kinase cascade, and p300 in LS-dependent regulation of KCa2.3 and KCa3.1 in ECs. Exposure to LS (15 dyn/cm²) for 24 h markedly increased KCa2.3 and KCa3.1 mRNA expression in cultured human coronary artery ECs (3.2 ± 0.4 and 45 ± 10 fold increase, respectively; P < 0.05 vs. static condition; n = 8-30), whereas oscillatory shear (OS; ± 5 dyn/cm² × 1 Hz) moderately increased KCa3.1 but did not affect KCa2.3. Expression of KCa2.1 and KCa2.2 was suppressed under both LS and OS conditions, whereas KCa1.1 was slightly elevated in LS and unchanged in OS. Inhibition of CaMKK attenuated LS-induced increases in the expression and channel activity of KCa2.3 and KCa3.1, and in phosphorylation of Akt (Ser473) and p300 (Ser1834). Inhibition of Akt abolished the upregulation of these channels by diminishing p300 phosphorylation. Consistently, disruption of the interaction of p300 with transcription factors eliminated the induction of these channels. Thus a CaMKK/Akt/p300 cascade plays an important role in LS-dependent induction of KCa2.3 and KCa3.1 expression, thereby regulating EC function and adaptation to hemodynamic changes.

  11. Buried wire gage for wall shear stress measurements

    NASA Technical Reports Server (NTRS)

    Murthy, V. S.; Rose, W. C.

    1978-01-01

    A buried wire gage for measuring wall shear stress in fluid flow was studied and further developed. Several methods of making this relatively new type of gage were examined to arrive at a successful technique that is well-suited for wind-tunnel testing. A series of measurements was made to demonstrate the adequacy of a two-point calibration procedure for these gages. The buried wire gage is also demonstrated to be ideally suited for quantitative measurement of wall shear stress in wind-tunnel testing.

  12. Strain stiffening and stress heterogeneities in sheared collagen networks

    NASA Astrophysics Data System (ADS)

    Urbach, Jeffrey

    2014-03-01

    Disordered networks of stiff or semi-flexible filaments display unusual mechanical properties, including dramatic stiffening when sheared, but little is known about the spatial distribution of stresses. This talk will introduce the technique of Boundary Stress Microscopy, which adapts the approach of traction force microscopy to rheological measurements in order to quantify the non-uniform surface stresses in sheared soft materials. Our results on networks of the biopolymer collagen, a major component of the extracellular matrix, show stress variations over length scales much larger than the network mesh size. We find that the heterogeneity increases with strain stiffening, with stresses at high strains exceeding average stresses by an order of magnitude. The strain stiffening behavior over a wide range of mesh sizes can be parameterized by a single characteristic strain and associated stress, which describes both the strain stiffening regime and network yielding. The characteristic stress is approximately proportional to network density, but the peak stress at both the characteristic strain and at yielding are remarkably insensitive to concentration. These results show the power of Boundary Stress Microscopy to reveal the nature of stress propagation in disordered soft materials, which is critical for understanding many important mechanical properties, including the ultimate strength of a material and the nature of appropriate microscopic constitutive equations. Supported by the AFOSR (FA9550-10-1-0473) and the NSF (DMR-0804782).

  13. Mass Transport and Shear Stress as Mediators of Flow Effects on Atherosclerotic Plaque Origin and Growth

    NASA Astrophysics Data System (ADS)

    Gorder, Riley; Aliseda, Alberto

    2009-11-01

    The carotid artery bifurcation (CAB) is one of the leading site for atherosclerosis, a major cause of mortality and morbidity in the developed world. The specific mechanisms by which perturbed flow at the bifurcation and in the carotid bulge promotes plaque formation and growth are not fully understood. Shear stress, mass transport, and flow residence times are considered dominant factors. Shear stress causes restructuring of endothelial cells at the arterial wall which changes the wall's permeability. Long residence times are associated with enhanced mass transport through increased diffusion of lipids and white blood cells into the arterial wall. Although momentum and mass transfer are traditionally coupled by correlations similar to Reynolds Analogy, the complex flow patterns present in this region due to the pulsatile, transitional, detached flow associated with the complex geometry makes the validity of commonly accepted assumptions uncertain. We create solid models of the CAB from MRI or ultrasound medical images, build flow phantoms on clear polyester resin and use an IOR matching, blood mimicking, working fluid. Using PIV and dye injection techniques the shear stress and scalar transport are experimentally investigated. Our goal is to establish a quantitative relationship between momentum and mass transfer under a wide range of physiologically normal and pathological conditions.

  14. Analysis of temporal shear stress gradients during the onset phase of flow over a backward-facing step.

    PubMed

    Haidekker, M A; White, C R; Frangos, J A

    2001-10-01

    Endothelial cells in blood vessels are exposed to bloodflow and thus fluid shear stress. In arterial bifurcations and stenoses, disturbed flow causes zones of recirculation and stagnation, which are associated with both spatial and temporal gradients of shear stress. Such gradients have been linked to the generation of atherosclerotic plaques. For in-vitro studies of endothelial cell responses, the sudden-expansion flow chamber has been widely used and described. A two-dimensional numerical simulation of the onset phase of flow through the chamber was performed. The wall shear stress action on the bottom plate was computed as a function of time and distance from the sudden expansion. The results showed that depending on the time for the flow to be established, significant temporal gradients occurred close to the second stagnation point of flow. Slowly ramping the flow over 15 s instead of 200 ms reduces the temporal gradients by a factor of 300, while spatial gradients are reduced by 23 percent. Thus, the effects of spatial and temporal gradients can be observed separately. In experiments on endothelial cells, disturbed flow stimulated cell proliferation only when flow onset was sudden. The spatial patterns of proliferation rate match the exposure to temporal gradients. This study provides information on the dynamics of spatial and temporal gradients to which the cells are exposed in a sudden-expansion flow chamber and relates them to changes in the onset phase of flow.

  15. Aspirin Has Limited Ability to Modulate Shear-Mediated Platelet Activation Associated with Elevated Shear Stress of Ventricular Assist Devices

    PubMed Central

    Valerio, Lorenzo; Tran, Phat L.; Sheriff, Jawaad; Brengle, William; Ghosh, Ram; Chiu, Wei-Che; Redaelli, Alberto; Fiore, Gianfranco B.; Pappalardo, Federico; Bluestein, Danny; Slepian, Marvin J.

    2016-01-01

    Continuous flow ventricular assist devices (cfVADs) while effective in advanced heart failure, remain plagued by thrombosis related to abnormal flows and elevated shear stress. To limit cfVAD thrombosis, patients utilize complex anti-thrombotic regimens built upon a foundation of aspirin (ASA). While much data exists on ASA as a modulator of biochemically-mediated platelet activation, limited data exists as to the efficacy of ASA as a means of limiting shear-mediated platelet activation, particularly under elevated shear stress common within cfVADs. We investigated the ability of ASA (20, 25 and 125 μM) to limit shear-mediated platelet activation under conditions of: 1) constant shear stress (30 dyne/cm2 and 70 dyne/cm2); 2) dynamic shear stress, and 3) initial high shear exposure (70 dyne/cm2) followed by low shear exposure – i.e. a platelet sensitization protocol, utilizing a hemodynamic shearing device providing uniform shear stress in vitro. The efficacy of ASA to limit platelet activation mediated via passage through a clinical cfVAD system (DeBakey Micromed) in vitro was also studied. ASA reduced platelet activation only under conditions of low shear stress (38% reduction compared to control, n = 10, p < 0.004), with minimal protection at higher shear stress and under dynamic conditions (n = 10, p > 0.5) with no limitation of platelet sensitization. ASA had limited ability (25.6% reduction in platelet activation rate) to modulate shear-mediated platelet activation induced via cfVAD passage. These findings, while performed under “deconstructed” non-clinical conditions by utilizing purified platelets alone in vitro, provide a potential contributory mechanistic explanation for the persistent thrombosis rates experienced clinically in cfVAD patients despite ASA therapy. An opportunity exists to develop enhanced pharmacologic strategies to limit shear-mediated platelet activation at elevated shear levels associated with mechanical circulatory support

  16. Neutrophil adhesion and crawling dynamics on liver sinusoidal endothelial cells under shear flow.

    PubMed

    Yang, Hao; Li, Ning; Du, Yu; Tong, Chunfang; Lü, Shouqin; Hu, Jinrong; Zhang, Yan; Long, Mian

    2017-02-01

    Neutrophil (polymorphonuclear leukocyte, PMN) recruitment in the liver sinusoid takes place in almost all liver diseases and contributes to pathogen clearance or tissue damage. While PMN rolling unlikely appears in liver sinusoids and Mac-1 or CD44 is assumed to play respective roles during in vivo local or systematic inflammatory stimulation, the regulating mechanisms of PMN adhesion and crawling dynamics are still unclear from those in vivo studies. Here we developed a two-dimensional in vitro sinusoidal model with primary liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) to investigate TNF-α-induced PMN recruitment under shear flow. Our data demonstrated that LFA-1 dominates the static or shear resistant adhesion of PMNs while Mac-1 decelerates PMN crawling on LSEC monolayer. Any one of LFA-1, Mac-1, and CD44 molecules is not able to work effectively for mediating PMN transmigration across LSEC monolayer. The presence of KCs only affects the randomness of PMN crawling. These findings further the understandings of PMN recruitment under shear flow in liver sinusoids.

  17. Acetaminophen protects brain endothelial cells against oxidative stress.

    PubMed

    Tripathy, Debjani; Grammas, Paula

    2009-05-01

    Increasing evidence suggests that acetaminophen has unappreciated anti-oxidant and anti-inflammatory properties. Drugs that affect oxidant and inflammatory stress in the brain are of interest because both processes are thought to contribute to the pathogenesis of neurodegenerative disease. The objective of this study is to determine whether acetaminophen affects the response of brain endothelial cells to oxidative stress. Cultured brain endothelial cells are pre-treated with acetaminophen and then exposed to the superoxide-generating compound menadione (25 microM). Cell survival, inflammatory protein expression, and anti-oxidant enzyme activity are measured. Menadione causes a significant (p<0.001) increase in endothelial cell death as well as an increase in RNA and protein levels of tumor necrosis factor alpha, interleukin-1, macrophage inflammatory protein alpha, and RANTES. Menadione also evokes a significant (p<0.001) increase in the activity of the anti-oxidant enzyme superoxide dismutase (SOD). Pre-treatment of endothelial cell cultures with acetaminophen (25-100 microM) increases endothelial cell survival and inhibits menadione-induced expression of inflammatory proteins and SOD activity. In addition, we document, for the first time, that acetaminophen increases expression of the anti-apoptotic protein Bcl2. Suppressing Bcl2 with siRNA blocks the pro-survival effect of acetaminophen. These data show that acetaminophen has anti-oxidant and anti-inflammatory effects on the cerebrovasculature and suggest a heretofore unappreciated therapeutic potential for this drug in neurodegenerative diseases such as Alzheimer's disease that are characterized by oxidant and inflammatory stress.

  18. A Two-Axis Direct Fluid Shear Stress Sensor

    NASA Technical Reports Server (NTRS)

    Adcock, Edward E.; Scott, Michael A.; Bajikar, Sateesh S.

    2010-01-01

    This innovation is a miniature or micro sized semiconductor sensor design that provides two axis direct non-intrusive measurement of skin friction or wall shear stress in fluid flow. The sensor is fabricated by micro-electro-mechanical system (MEMS) technology, enabling small size and low cost reproductions. The sensors have been fabricated by utilizing MEMS fabrication processes to bond a sensing element wafer to a fluid coupling wafer. This layering technique provides for an out of plane dimension that is on the same order of length as the inplane dimensions. The sensor design has the following characteristics: a shear force collecting plate with dimensions that can be tailored to various application specific requirements such as spatial resolution, temporal resolution and shear force range and resolution. This plate is located coplanar to both the sensor body and flow boundary, and is connected to a dual axis gimbal structure by a connecting column or lever arm. The dual axis gimbal structure has torsional hinges with embedded piezoresistive torsional strain gauges which provide a voltage output that is correlated to the applied shear stress (and excitation current) on force collection plate that is located on the flow boundary surface (hence the transduction method). This combination of design elements create a force concentration and resolution structure that enables the generation of a large stress on the strain gauge from the small shear stress on the flow boundary wall. This design as well as the use of back side electrical contacts establishes a non-intrusive method to quantitatively measure the shear force vector on aerodynamic bodies.

  19. Liquid Crystals Indicate Directions Of Surface Shear Stresses

    NASA Technical Reports Server (NTRS)

    Reda, Daniel C.

    1996-01-01

    Report consisting of main text of U.S. Patent 5,394,752 presents detailed information on one aspect of method of using changes in colors of liquid-crystal coatings to indicate instantaneous directions of flow-induced shear stresses (skin friction) on aerodynamic surfaces.

  20. Calculation of Near-Bank Velocity and Boundary Shear Stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Detailed knowledge of the flow and boundary shear stress fields near the banks of natural channels is essential for making accurate calculations of rates of near-bank sediment transport and geomorphic adjustment. This paper presents a test of a relatively simple, fully predictive, numerical method f...

  1. Incomplete restoration of homeostatic shear stress within arteriovenous fistulae.

    PubMed

    McGah, Patrick M; Leotta, Daniel F; Beach, Kirk W; Eugene Zierler, R; Aliseda, Alberto

    2013-01-01

    Arteriovenous fistulae are surgically created to provide adequate access for dialysis patients suffering from end-stage renal disease. It has long been hypothesized that the rapid blood vessel remodeling occurring after fistula creation is, in part, a process to restore the mechanical stresses to some preferred level, i.e., mechanical homeostasis. We present computational hemodynamic simulations in four patient-specific models of mature arteriovenous fistulae reconstructed from 3D ultrasound scans. Our results suggest that these mature fistulae have remodeled to return to ''normal'' shear stresses away from the anastomoses: about 1.0 Pa in the outflow veins and about 2.5 Pa in the inflow arteries. Large parts of the anastomoses were found to be under very high shear stresses >15 Pa, over most of the cardiac cycle. These results suggest that the remodeling process works toward restoring mechanical homeostasis in the fistulae, but that the process is limited or incomplete, even in mature fistulae, as evidenced by the elevated shear at or near the anastomoses. Based on the long term clinical viability of these dialysis accesses, we hypothesize that the elevated nonhomeostatic shear stresses in some portions of the vessels were not detrimental to fistula patency.

  2. Production of Functional Proteins: Balance of Shear Stress and Gravity

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas John (Inventor); Hammond, Timothy Grant (Inventor); Haysen, James Howard (Inventor)

    2005-01-01

    The present invention provides for a method of culturing cells and inducing the expression of at least one gene in the cell culture. The method provides for contacting the cell with a transcription factor decoy oligonucleotide sequence directed against a nucleotide sequence encoding a shear stress response element.

  3. Signatures of deterministic chaos in dyslipidemic erythrocytes under shear stress.

    PubMed

    Korol, A M; Rasia, R

    2003-03-01

    The erythrocytes deformation under shear stress, the viscoelastic properties and the effects observed on healthy donors and on dyslipidemic patients are investigated from the point of view of nonlinear dynamics. Finally it is suggested that the different results obtained could be useful with regard to pathophysiological disturbances and their treatment.

  4. A fluidized bed technique for estimating soil critical shear stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Soil erosion models, depending on how they are formulated, always have erodibilitiy parameters in the erosion equations. For a process-based model like the Water Erosion Prediction Project (WEPP) model, the erodibility parameters include rill and interrill erodibility and critical shear stress. Thes...

  5. The Need for a Shear Stress Calibration Standard

    NASA Technical Reports Server (NTRS)

    Scott, Michael A.

    2004-01-01

    By surveying current research of various micro-electro mechanical systems (MEMS) shear stress sensor development efforts we illustrate the wide variety of methods used to test and characterize these sensors. The different methods of testing these sensors make comparison of results difficult in some cases, and also this comparison is further complicated by the different formats used in reporting the results of these tests. The fact that making these comparisons can be so difficult at times clearly illustrates a need for standardized testing and reporting methodologies. This need indicates that the development of a national or international standard for the calibration of MEMS shear stress sensors should be undertaken. As a first step towards the development of this standard, two types of devices are compared and contrasted. The first type device is a laminar flow channel with two different versions considered: the first built with standard manufacturing techniques and the second with advanced precision manufacturing techniques. The second type of device is a new concept for creating a known shear stress consisting of a rotating wheel with the sensor mounted tangentially to the rim and positioned in close proximity to the rim. The shear stress generated by the flow at the sensor position is simply tau = (mu)r(omega)/h, where mu is the viscosity of the ambient gas, r the wheel radius, omega the angular velocity of the wheel, and h the width of the gap between the wheel rim and the sensor. Additionally, issues related to the development of a standard for shear stress calibration are identified and discussed.

  6. Role of fluid shear stress in regulating VWF structure, function and related blood disorders.

    PubMed

    Gogia, Shobhit; Neelamegham, Sriram

    2015-01-01

    Von Willebrand factor (VWF) is the largest glycoprotein in blood. It plays a crucial role in primary hemostasis via its binding interaction with platelet and endothelial cell surface receptors, other blood proteins and extra-cellular matrix components. This protein is found as a series of repeat units that are disulfide bonded to form multimeric structures. Once in blood, the protein multimer distribution is dynamically regulated by fluid shear stress which has two opposing effects: it promotes the aggregation or self-association of multiple VWF units, and it simultaneously reduces multimer size by facilitating the force-dependent cleavage of the protein by various proteases, most notably ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type repeats, motif 1 type 13). In addition to these effects, fluid shear also controls the solution and substrate-immobilized structure of VWF, the nature of contact between blood platelets and substrates, and the biomechanics of the GpIbα-VWF bond. These features together regulate different physiological and pathological processes including normal hemostasis, arterial and venous thrombosis, von Willebrand disease, thrombotic thrombocytopenic purpura and acquired von Willebrand syndrome. This article discusses current knowledge of VWF structure-function relationships with emphasis on the effects of hydrodynamic shear, including rapid methods to estimate the nature and magnitude of these forces in selected conditions. It shows that observations made by many investigators using solution and substrate-based shearing devices can be reconciled upon considering the physical size of VWF and the applied mechanical force in these different geometries.

  7. Development of a shear stress sensor to analyse the influence of polymers on the turbulent wall shear stress

    NASA Astrophysics Data System (ADS)

    Nottebrock, Bernardo; Große, Sebastian; Schröder, Wolfgang

    2011-05-01

    The drag reducing effect of polymers in a channel flow is well known and it is assumed that the polymer filaments interfere with the turbulent structures in the very near-wall flow. To analyse their precise effect, a micro-pillar shear stress sensor (MPS3) measurement system is developed which allows the detection of wall shear stress at high spatial and temporal resolutions. Different manufacturing techniques for the required micro-pillars are discussed and their influence on the flow is investigated evidencing the non-intrusive character of the pillars. Subsequently, a complete calibration is presented to relate the recorded deflection to wall shear stress values and to assure the correct detection over the whole expected frequency spectrum. A feasibility study about the ability to visualize the two-dimensional wall shear stress distribution completes the discussion about the validity of MPS3. In the last step, the drag reduction of a polymer filament grafted on a micro-pillar compared to a plain pillar and the application of MPS3 in an ocean-type polymer solution are investigated. The results confirm the expected behaviour found in the literature.

  8. Arrest stress of uniformly sheared wet granular matter

    NASA Astrophysics Data System (ADS)

    Ebrahimnazhad Rahbari, S. H.; Brinkmann, M.; Vollmer, J.

    2015-06-01

    We conduct extensive independent numerical experiments considering frictionless disks without internal degrees of freedom (rotation, etc.) in two dimensions. We report here that for a large range of the packing fractions below random-close packing, all components of the stress tensor of wet granular materials remain finite in the limit of zero shear rate. This is direct evidence for a fluid-to-solid arrest transition. The offset value of the shear stress characterizes plastic deformation of the arrested state which corresponds to dynamic yield stress of the system. Based on an analytical line of argument, we propose that the mean number of capillary bridges per particle, ν , follows a nontrivial dependence on the packing fraction, ϕ , and the capillary energy, ɛ . Most noticeably, we show that ν is a generic and universal quantity which does not depend on the driving protocol. Using this universal quantity, we calculate the arrest stress, σa, analytically based on a balance of the energy injection rate due to the external force driving the flow and the dissipation rate accounting for the rupture of capillary bridges. The resulting prediction of σa is a nonlinear function of the packing fraction, ϕ , and the capillary energy, ɛ . This formula provides an excellent, parameter-free prediction of the numerical data. Corrections to the theory for small and large packing fractions are connected to the emergence of shear bands and of contributions to the stress from repulsive particle interactions, respectively.

  9. The Role of Shear Failure on Stress Characterization

    NASA Astrophysics Data System (ADS)

    Chan, A. W.; Hauser, M.; Couzens-Schultz, B. A.; Gray, G.

    2014-09-01

    Leak-off pressure and lost circulation data are generally thought to be reflective of minimum stress. We propose an alternative interpretation should be considered where the data may reflect a shear failure along zones of pre-existing weakness rather than opening of tensile fractures against the minimum stress. This mechanism has been discussed in a small number of borehole stability and hydraulic fracture papers, but has not been widely applied to leak-off test or lost circulation interpretation. In this paper, we will revisit and expand the concept introduced recently by Couzens-Schultz and Chan (J Struct Geol, doi: 10.1016/j.jsg.2010.06.013, 2010) based on abnormally low leak-off tests in an active thrust belt to the analysis of lost circulation observations in modern-day deltaic environments. In the Gulf of Mexico, lost circulations historically are interpreted as a representation of the minimum horizontal stress due to initiating or reopening of a fracture in tensile mode. However, shear failure or fault reactivation can occur at pressures well below the minimum far-field stress that is typically considered a safe upper bound for mud pressure if pre-existing planes of weakness such as faults or fracture networks exist. We demonstrated a mud loss event is shown to be inconsistent with the tensile failure mode in a normal stress environment, but in good agreement with expectations for shear failure along pre-existing faults.

  10. Normal stress differences in a sheared gas-solid suspension

    NASA Astrophysics Data System (ADS)

    Saha, Saikat; Alam, Meheboob

    2016-11-01

    The stress tensor and normal stress differences are analyzed for a homogeneously sheared gas-solid suspension using Enskog-Boltzmann equation. Inelastic particles are suspended in a viscous fluid of viscosity μf and experience a Stokes drag force. Viscous heating due to shear is compensated by (i) the inelastic collisions between particles and (ii) the drag force experienced by the particles due to the interstitial fluid. Rheology of the particle phase is analyzed with anisotropic-Gaussian as the single particle distribution function. The first (N1) and second (N2) normal stress differences are computed as functions of the density (ν), Stokes number (St) and restitution coefficient (e). A comparison with the existing simulation data shows an excellent agreement for both N1 and N2 over the predictions from other Grad-level theories. Finally, in the limit of St -> ∞ (μf -> 0), the related results from the conventional theory of dry granular flows are recovered.

  11. Sensor for Boundary Shear Stress in Fluid Flow

    NASA Technical Reports Server (NTRS)

    Bao, Xiaoqi; Badescu, Mircea; Sherrit, Stewart; Bar-Cohen, Yoseph; Lih, Shyh-Shiuh; Chang, Zensheu; Trease, Brian P.; Kerenyi, Kornel; Widholm, Scott E.; Ostlund, Patrick N.

    2012-01-01

    The formation of scour patterns at bridge piers is driven by the forces at the boundary of the water flow. In most experimental scour studies, indirect processes have been applied to estimate the shear stress using measured velocity profiles. The estimations are based on theoretical models and associated assumptions. However, the turbulence flow fields and boundary layer in the pier-scour region are very complex and lead to low-fidelity results. In addition, available turbulence models cannot account accurately for the bed roughness effect. Direct measurement of the boundary shear stress, normal stress, and their fluctuations are attractive alternatives. However, most direct-measurement shear sensors are bulky in size or not compatible to fluid flow. A sensor has been developed that consists of a floating plate with folded beam support and an optical grid on the back, combined with a high-resolution optical position probe. The folded beam support makes the floating plate more flexible in the sensing direction within a small footprint, while maintaining high stiffness in the other directions. The floating plate converts the shear force to displacement, and the optical probe detects the plate s position with nanometer resolution by sensing the pattern of the diffraction field of the grid through a glass window. This configuration makes the sensor compatible with liquid flow applications.

  12. Evolution of the wall shear stresses during the progressive enlargement of symmetric abdominal aortic aneurysms

    NASA Astrophysics Data System (ADS)

    Salsac, A.-V.; Sparks, S. R.; Chomaz, J.-M.; Lasheras, J. C.

    2006-08-01

    The changes in the evolution of the spatial and temporal distribution of the wall shear stresses (WSS) and gradients of wall shear stresses (GWSS) at different stages of the enlargement of an abdominal aortic aneurysm (AAA) are important in understanding the aetiology and progression of this vascular disease since they affect the wall structural integrity, primarily via the changes induced on the shape, functions and metabolism of the endothelial cells. Particle image velocimetry (PIV) measurements were performed in in vitro aneurysm models, while changing their geometric parameters systematically. It has been shown that, even at the very early stages of the disease, i.e. increase in the diameter ≤ 50%, the flow separates from the wall and a large vortex ring, usually followed by internal shear layers, is created. These lead to the generation of WSS that drastically differ in mean and fluctuating components from the healthy vessel. Inside the AAA, the mean WSS becomes negative along most of the aneurysmal wall and the magnitude of the WSS can be as low as 26% of the value in a healthy abdominal aorta.

  13. Efavirenz Causes Oxidative Stress, Endoplasmic Reticulum Stress, and Autophagy in Endothelial Cells.

    PubMed

    Weiß, Marlene; Kost, Bernd; Renner-Müller, Ingrid; Wolf, Eckhard; Mylonas, Ioannis; Brüning, Ansgar

    2016-01-01

    The non-nucleoside reverse transcriptase inhibitor efavirenz is a widely prescribed antiretroviral drug used in combined antiretroviral therapy. Despite being an essential and life-saving medication, the required lifelong use of HIV drugs has been associated with a variety of adverse effects, including disturbances in lipid metabolism and increased cardiovascular risk. Efavirenz belongs to those HIV drugs for which cardiovascular and endothelial dysfunctions have been reported. It is here shown that elevated concentrations of efavirenz can inhibit endothelial meshwork formation on extracellular matrix gels by normal and immortalized human umbilical vein cells. This inhibition was associated with an increase in oxidative stress markers, endoplasmic reticulum (ER) stress markers, and autophagy. Induction of ER stress occurred at pharmacologically relevant concentrations of efavirenz and resulted in reduced proliferation and cell viability of endothelial cells, which worsened in the presence of elevated efavirenz concentrations. In combination with the HIV protease inhibitor nelfinavir, both oxidative stress and ER stress became elevated in endothelial cells. These data indicate that pharmacologically relevant concentrations of efavirenz can impair cell viability of endothelial cells and that these effects may be aggravated by either elevated concentrations of efavirenz or by a combined use of efavirenz with other oxidative stress-inducing medications.

  14. Toll-like receptor 4-induced endoplasmic reticulum stress contributes to endothelial dysfunction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Impairment of vasodilator action of insulin is associated with endothelial dysfunction and insulin resistance. Endoplasmic reticulum (ER) stress is implicated as one of the mechanisms for pathophysiology of various cardiometabolic syndromes, including insulin resistance and endothelial dysfunction. ...

  15. Caveolin-1 regulates shear stress-dependent activation of extracellular signal-regulated kinase

    NASA Technical Reports Server (NTRS)

    Park, H.; Go, Y. M.; Darji, R.; Choi, J. W.; Lisanti, M. P.; Maland, M. C.; Jo, H.

    2000-01-01

    Fluid shear stress activates a member of the mitogen-activated protein (MAP) kinase family, extracellular signal-regulated kinase (ERK), by mechanisms dependent on cholesterol in the plasma membrane in bovine aortic endothelial cells (BAEC). Caveolae are microdomains of the plasma membrane that are enriched with cholesterol, caveolin, and signaling molecules. We hypothesized that caveolin-1 regulates shear activation of ERK. Because caveolin-1 is not exposed to the outside, cells were minimally permeabilized by Triton X-100 (0.01%) to deliver a neutralizing, polyclonal caveolin-1 antibody (pCav-1) inside the cells. pCav-1 then bound to caveolin-1 and inhibited shear activation of ERK but not c-Jun NH(2)-terminal kinase. Epitope mapping studies showed that pCav-1 binds to caveolin-1 at two regions (residues 1-21 and 61-101). When the recombinant proteins containing the epitopes fused to glutathione-S-transferase (GST-Cav(1-21) or GST-Cav(61-101)) were preincubated with pCav-1, only GST-Cav(61-101) reversed the inhibitory effect of the antibody on shear activation of ERK. Other antibodies, including m2234, which binds to caveolin-1 residues 1-21, had no effect on shear activation of ERK. Caveolin-1 residues 61-101 contain the scaffolding and oligomerization domains, suggesting that binding of pCav-1 to these regions likely disrupts the clustering of caveolin-1 or its interaction with signaling molecules involved in the shear-sensitive ERK pathway. We suggest that caveolae-like domains play a critical role in the mechanosensing and/or mechanosignal transduction of the ERK pathway.

  16. Relationship of oxidative stress and endothelial dysfunction in sleep apnoea.

    PubMed

    Jurado-Gámez, B; Fernandez-Marin, M C; Gómez-Chaparro, J L; Muñoz-Cabrera, L; Lopez-Barea, J; Perez-Jimenez, F; Lopez-Miranda, J

    2011-04-01

    The aim of the present study was to evaluate ischaemic reactive hyperaemia (IRH) in obstructive sleep apnoea (OSA) and its relationship with oxidative stress. We studied 69 consecutive patients referred to our Sleep Unit (Reina Sofia University Hospital, Cordoba, Spain). Patients with chronic diseases or those taking medication were excluded. IRH was assessed before and after polysomnography. Morning IRH and oxidative stress markers were compared between patients with (apnoea-hypopnoea index (AHI) ≥ 5) and without (AHI < 5) OSA. Measurements were repeated in 25 severe OSA patients after continuous positive airway pressure (CPAP) therapy. We included 46 OSA patients (mean ± sd AHI 49 ± 32.1) and 23 non-OSA subjects (AHI 3 ± 0.9). The OSA patients showed a significant worsening of morning IRH, and a significant increase in malondialdehyde and 8-hydroxydeoxyguanosine levels. Only the oxygen desaturation index independently explained morning IRH, while malondialdehyde levels showed a weak effect on IRH. In severe OSA patients, IRH improved significantly after CPAP treatment, as did malondialdehyde, 8-hydroxydeoxyguanosine and protein carbonyl levels. In OSA patients, endothelial dysfunction and oxidative stress were observed, and IRH worsened after sleep. The increase in oxidative stress was not associated with IRH, while intermittent hypoxia was strongly associated with IRH. In severe OSA patients, CPAP treatment improved oxidative stress and endothelial function.

  17. Protein kinase B/Akt activates c-Jun NH(2)-terminal kinase by increasing NO production in response to shear stress

    NASA Technical Reports Server (NTRS)

    Go, Y. M.; Boo, Y. C.; Park, H.; Maland, M. C.; Patel, R.; Pritchard, K. A. Jr; Fujio, Y.; Walsh, K.; Darley-Usmar, V.; Jo, H.

    2001-01-01

    Laminar shear stress activates c-Jun NH(2)-terminal kinase (JNK) by the mechanisms involving both nitric oxide (NO) and phosphatidylinositide 3-kinase (PI3K). Because protein kinase B (Akt), a downstream effector of PI3K, has been shown to phosphorylate and activate endothelial NO synthase, we hypothesized that Akt regulates shear-dependent activation of JNK by stimulating NO production. Here, we examined the role of Akt in shear-dependent NO production and JNK activation by expressing a dominant negative Akt mutant (Akt(AA)) and a constitutively active mutant (Akt(Myr)) in bovine aortic endothelial cells (BAEC). As expected, pretreatment of BAEC with the PI3K inhibitor (wortmannin) prevented shear-dependent stimulation of Akt and NO production. Transient expression of Akt(AA) in BAEC by using a recombinant adenoviral construct inhibited the shear-dependent stimulation of NO production and JNK activation. However, transient expression of Akt(Myr) by using a recombinant adenoviral construct did not induce JNK activation. This is consistent with our previous finding that NO is required, but not sufficient on its own, to activate JNK in response to shear stress. These results and our previous findings strongly suggest that shear stress triggers activation of PI3K, Akt, and endothelial NO synthase, leading to production of NO, which (along with O(2-), which is also produced by shear) activates Ras-JNK pathway. The regulation of Akt, NO, and JNK by shear stress is likely to play a critical role in its antiatherogenic effects.

  18. Demonstration of actin filament stress fibers in microvascular endothelial cells in situ.

    PubMed

    Nehls, V; Drenckhahn, D

    1991-07-01

    We have developed a method for immunostaining the microvascular tree of rat mesenteric windows in situ. The procedure consists of three steps, i.e., mild fixation with formaldehyde, controlled proteolytic digestion of the mesothelial layer, and permeabilization with acetone. Discrimination between different microvascular segments was possible by double-fluorescent staining with antibodies to the smooth muscle isoform of alpha-actin and to nonmuscle myosin from platelets. Antibodies to nonmuscle myosin labeled numerous longitudinally oriented cables in endothelial cells of all microvascular segments (arterioles, metarterioles, pre-, mid-, and postcapillaries, small venules). Occasionally, the myosin-containing cables displayed the interrupted sarcomere-like staining pattern that is diagnostic for stress fibers. In contrast, staining of actin filaments with phalloidin-rhodamin resulted in a noninterrupted, continuous fluorescence of the stress fibers. A possible functional role of microvascular endothelial stress fibers is to serve as a tensile cytoskeletal scaffold that stabilizes the tubular, three-dimensional geometry of microvessels and, in addition, to help the endothelium resist the shear forces created by blood flow and by collision with red and white blood cells.

  19. Evaluation of the time dependent surface shear stress in turbulent flows

    NASA Technical Reports Server (NTRS)

    Sandborn, V. A.

    1979-01-01

    The time dependent surface shear stress has been evaluated using surface heat transfer measurements. For fully developed turbulent pipe and open channel water flows, and incompressible and compressible turbulent boundary layer air flows the measurements indicate the absolute magnitude of the surface shear stress fluctuations will be greater than two times the mean values. The root-mean-square shear stress fluctuations were of the order of 0.2 to 0.4 times the mean surface shear values. Due to these large surface shear stress fluctuations and the nonlinear relation between heat transfer and shear stress, a special technique has been developed to evaluate the measurements. It was found that the non-linear averaging errors for a hot film-surface shear stress gauge in a fully developed pipe flow was of the order of 10 percent at low velocities. A hot wire-surface shear stress gauge was employed for measurements of turbulent boundary layers in air.

  20. Measurement of the temperature-dependent threshold shear-stress of red blood cell aggregation

    NASA Astrophysics Data System (ADS)

    Lim, Hyun-Jung; Nam, Jeong-Hun; Lee, Yong-Jin; Shin, Sehyun

    2009-09-01

    Red blood cell (RBC) aggregation is becoming an important hemorheological parameter, which typically exhibits temperature dependence. Quite recently, a critical shear-stress was proposed as a new dimensional index to represent the aggregative and disaggregative behaviors of RBCs. The present study investigated the effect of the temperature on the critical shear-stress that is required to keep RBC aggregates dispersed. The critical shear-stress was measured at various temperatures (4, 10, 20, 30, and 37 °C) through the use of a transient microfluidic aggregometry. The critical shear-stress significantly increased as the blood temperature lowered, which accorded with the increase in the low-shear blood viscosity with the lowering of the temperature. Furthermore, the critical shear-stress also showed good agreement with the threshold shear-stress, as measured in a rotational Couette flow. These findings assist in rheologically validating the critical shear-stress, as defined in the microfluidic aggregometry.

  1. Inverse method for estimating shear stress in machining

    NASA Astrophysics Data System (ADS)

    Burns, T. J.; Mates, S. P.; Rhorer, R. L.; Whitenton, E. P.; Basak, D.

    2016-01-01

    An inverse method is presented for estimating shear stress in the work material in the region of chip-tool contact along the rake face of the tool during orthogonal machining. The method is motivated by a model of heat generation in the chip, which is based on a two-zone contact model for friction along the rake face, and an estimate of the steady-state flow of heat into the cutting tool. Given an experimentally determined discrete set of steady-state temperature measurements along the rake face of the tool, it is shown how to estimate the corresponding shear stress distribution on the rake face, even when no friction model is specified.

  2. Mathematical Modeling of Intravascular Blood Coagulation under Wall Shear Stress

    PubMed Central

    Rukhlenko, Oleksii S.; Dudchenko, Olga A.; Zlobina, Ksenia E.; Guria, Georgy Th.

    2015-01-01

    Increased shear stress such as observed at local stenosis may cause drastic changes in the permeability of the vessel wall to procoagulants and thus initiate intravascular blood coagulation. In this paper we suggest a mathematical model to investigate how shear stress-induced permeability influences the thrombogenic potential of atherosclerotic plaques. Numerical analysis of the model reveals the existence of two hydrodynamic thresholds for activation of blood coagulation in the system and unveils typical scenarios of thrombus formation. The dependence of blood coagulation development on the intensity of blood flow, as well as on geometrical parameters of atherosclerotic plaque is described. Relevant parametric diagrams are drawn. The results suggest a previously unrecognized role of relatively small plaques (resulting in less than 50% of the lumen area reduction) in atherothrombosis and have important implications for the existing stenting guidelines. PMID:26222505

  3. Liquid crystals for unsteady surface shear stress visualization

    SciTech Connect

    Reda, D.C.

    1988-01-01

    Oscillating airfoil experiments were conducted to test the frequency response of thermochromic liquid crystal coatings to unsteady surface shear stresses under isothermal-flow conditions. The model was an NACA-0015 airfoil, exposed to an incompressible flow at a freestream Reynolds number (based on chord) of 1.14 x 10/sup 6/. Angle-of-attack forcing functions were sine waves of amplitude +- 10/degree/ about each of three mean angles of attack: 0/degree/, 10/degree/, and 20/degree/. Frequencies of oscillation were 0.2, 0.6 and 1.2 hertz, corresponding to reduced frequencies of 0.0055, 0.0164 and 0.0328. Data acquisition was accomplished by video recording. Observations showed the liquid crystal technique capable of visualizing high surface shear stress zones over the stated dynamic range in a continuous and reversible manner. 11 refs.

  4. Wall shear stress measurements using a new transducer

    NASA Technical Reports Server (NTRS)

    Vakili, A. D.; Wu, J. M.; Lawing, P. L.

    1986-01-01

    A new instrument has been developed for direct measurement of wall shear stress. This instrument is simple and symmetric in design with small moving mass and no internal friction. Features employed in the design of this instrument eliminate most of the difficulties associated with the traditional floating element balances. Vibration problems associated with the floating element skin friction balances have been found to be minimized by the design features and optional damping provided. The unique design of this instrument eliminates or reduces the errors associated with conventional floating-element devices: such as errors due to gaps, pressure gradient, acceleration, heat transfer and temperature change. The instrument is equipped with various sensing systems and the output signal is a linear function of the wall shear stress. Measurement made in three different tunnels show good agreement with theory and data obtained by the floating element devices.

  5. Limiting shear stress and monotonic properties of liquid water

    NASA Astrophysics Data System (ADS)

    Gorshkov, A. I.

    2016-12-01

    Publications in scientific journals in which the authors attempt to experimentally prove that water, the most widespread substance on the Earth, is not a completely classical liquid, have become more frequent recently. This means, first, that water behaves as a solid at very low shear stress, i.e., does not flow, and, second, that the temperature dependences of its different properties are non-monotonic, i.e., possess singularities. We are aware of several such publications [1-5].

  6. Non-volcanic tremor driven by large transient shear stresses

    USGS Publications Warehouse

    Rubinstein, J.L.; Vidale, J.E.; Gomberg, J.; Bodin, P.; Creager, K.C.; Malone, S.D.

    2007-01-01

    Non-impulsive seismic radiation or 'tremor' has long been observed at volcanoes and more recently around subduction zones. Although the number of observations of non-volcanic tremor is steadily increasing, the causative mechanism remains unclear. Some have attributed non-volcanic tremor to the movement of fluids, while its coincidence with geodetically observed slow-slip events at regular intervals has led others to consider slip on the plate interface as its cause. Low-frequency earthquakes in Japan, which are believed to make up at least part of non-volcanic tremor, have focal mechanisms and locations that are consistent with tremor being generated by shear slip on the subduction interface. In Cascadia, however, tremor locations appear to be more distributed in depth than in Japan, making them harder to reconcile with a plate interface shear-slip model. Here we identify bursts of tremor that radiated from the Cascadia subduction zone near Vancouver Island, Canada, during the strongest shaking from the moment magnitude Mw = 7.8, 2002 Denali, Alaska, earthquake. Tremor occurs when the Love wave displacements are to the southwest (the direction of plate convergence of the overriding plate), implying that the Love waves trigger the tremor. We show that these displacements correspond to shear stresses of approximately 40 kPa on the plate interface, which suggests that the effective stress on the plate interface is very low. These observations indicate that tremor and possibly slow slip can be instantaneously induced by shear stress increases on the subduction interface - effectively a frictional failure response to the driving stress. ??2007 Nature Publishing Group.

  7. Non-volcanic tremor driven by large transient shear stresses.

    PubMed

    Rubinstein, Justin L; Vidale, John E; Gomberg, Joan; Bodin, Paul; Creager, Kenneth C; Malone, Stephen D

    2007-08-02

    Non-impulsive seismic radiation or 'tremor' has long been observed at volcanoes and more recently around subduction zones. Although the number of observations of non-volcanic tremor is steadily increasing, the causative mechanism remains unclear. Some have attributed non-volcanic tremor to the movement of fluids, while its coincidence with geodetically observed slow-slip events at regular intervals has led others to consider slip on the plate interface as its cause. Low-frequency earthquakes in Japan, which are believed to make up at least part of non-volcanic tremor, have focal mechanisms and locations that are consistent with tremor being generated by shear slip on the subduction interface. In Cascadia, however, tremor locations appear to be more distributed in depth than in Japan, making them harder to reconcile with a plate interface shear-slip model. Here we identify bursts of tremor that radiated from the Cascadia subduction zone near Vancouver Island, Canada, during the strongest shaking from the moment magnitude M(w) = 7.8, 2002 Denali, Alaska, earthquake. Tremor occurs when the Love wave displacements are to the southwest (the direction of plate convergence of the overriding plate), implying that the Love waves trigger the tremor. We show that these displacements correspond to shear stresses of approximately 40 kPa on the plate interface, which suggests that the effective stress on the plate interface is very low. These observations indicate that tremor and possibly slow slip can be instantaneously induced by shear stress increases on the subduction interface-effectively a frictional failure response to the driving stress.

  8. Basal shear stress of debris flow in the runout phase

    NASA Astrophysics Data System (ADS)

    D'Agostino, V.; Bettella, F.; Cesca, M.

    2013-11-01

    A laboratory device is proposed to assess the basal shear stresses generated by debris-flow mixtures during their runout phase. The device consists of an inclinable box with a gate facing a deposition plane. The box is filled with a selected debris-flow mixture, and after sudden opening of the gate, the features of the dam-break deposit can be measured. Based on some simplified assumptions of the energy balance, a methodology is proposed to assess basal shear stresses. The device has been tested using sediment samples from debris-flow deposits generated by two catchments of the Dolomites (Cortina d'Ampezzo, Belluno, Italy) by carrying out runout tests for different sediment concentrations by volume. The results show how the static Coulomb friction law is valid in the runout phase, with friction angles on the order of the angle of repose of the same material in dry conditions. The data elaboration also yields an innovative constitutive equation for shear stresses. This relation merges the Coulomb mixture approach with the concept of a one-phase flow with a certain rheology. This integration offers a useful insight into the weaknesses of the rheological approach if it is not properly scaled up to the ambient pressure of interest.

  9. Polyphenols action against oxidative stress formation in endothelial cells.

    PubMed

    Łuczaj, Wojciech; Zapora, Ewa; Szczepański, Marek; Wnuczko, Krzysztof; Skrzydlewska, Elzbieta

    2009-01-01

    The aim of this study was to investigate the influence of epigallocatechin-3-gallate (EGCG), theaflavins (TFs) and black tea extract (BTE) on oxidative stress formation as well as on antioxidant system of human vein endothelial cells (HUVEC). HUVEC were incubated for 0,5 h with 100 mM tert-butyl hydroperoxide (t-BHP) for oxidative stress formation. The influence of EGCG, TFs, and BTE on oxidative stress and antioxidant system parameters was investigated by the pre-incubation for 2 h with 50 mg/mL of each compound. Half hour exposure to t-BHP caused statistically significant decrease in GSH-Px activity and in the content of GSH, vitamin A, vitamin E as well as tryptophan. Moreover, pretreatment of cells with t-BHP caused statistically significant increase in activities of Cu,Zn-SOD, GSSG-R and in the level of MDA and dityrosine. Pretreated with t-BHP endothelial cells, subjected to EGCG, TFs and black tea extract, are partially protected against oxidative activity of t-BHP causing statistically significant increase in GSH-Px activity, GSH and tryptophan level and decrease in MDA and dityrosine level in comparison with HUVEC pretreated with t-BHP group. These results indicate the beneficial effect of tea polyphenolic compounds on HUVEC antioxidant abilities and, in consequence, their protective effect in cell components.

  10. Molecular Origins of Higher Harmonics in Large-Amplitude Oscillatory Shear Flow: Shear Stress Response

    NASA Astrophysics Data System (ADS)

    Gilbert, Peter; Giacomin, A. Jeffrey; Schmalzer, Andrew; Bird, R. B.

    Recent work has focused on understanding the molecular origins of higher harmonics that arise in the shear stress response of polymeric liquids in large-amplitude oscillatory shear flow. These higher harmonics have been explained using only the orientation distribution of a dilute suspension of rigid dumbbells in a Newtonian fluid, which neglects molecular interactions and is the simplest relevant molecular model of polymer viscoelasticity [R.B. Bird et al., J Chem Phys, 140, 074904 (2014)]. We explore these molecular interactions by examining the Curtiss-Bird model, a kinetic molecular theory that accounts for restricted polymer motions arising when chains are concentrated [Fan and Bird, JNNFM, 15, 341 (1984)]. For concentrated systems, the chain motion transverse to the chain axis is more restricted than along the axis. This anisotropy is described by the link tension coefficient, ɛ, for which several special cases arise: ɛ =0 corresponds to reptation, ɛ > 1 1 8 8 to rod-climbing, 1 1 2 2 >= ɛ >= 3 3 4 4 to reasonable shear-thinning predictions in steady simple shear flow, and ɛ =1 to a dilute solution of chains. We examine the shapes of the shear stress versus shear rate loops for the special cases, ɛ = 0 , 1 0 , 1 8 , 3 3 8 8 8 , 3 3 8 8 , 1 , of the Curtiss-Bird model, and we compare these with those

  11. ESTIMATION OF EFFECTIVE SHEAR STRESS WORKING ON FLAT SHEET MEMBRANE USING FLUIDIZED MEDIA IN MBRs

    NASA Astrophysics Data System (ADS)

    Zaw, Hlwan Moe; Li, Tairi; Nagaoka, Hiroshi; Mishima, Iori

    This study was aimed at estimating effective shear stress working on flat sheet membrane by the addition of fluidized media in MBRs. In both of laboratory-scale aeration tanks with and without fluidized media, shear stress variations on membrane surface and water phase velocity variations were measured and MBR operation was conducted. For the evaluation of the effective shear stress working on membrane surface to mitigate membrane surface, simulation of trans-membrane pressure increase was conducted. It was shown that the time-averaged absolute value of shear stress was smaller in the reactor with fluidized media than without fluidized media. However, due to strong turbulence in the reactor with fluidized media caused by interaction between water-phase and media and also due to the direct interaction between membrane surface and fluidized media, standard deviation of shear stress on membrane surface was larger in the reactor with fluidized media than without media. Histograms of shear stress variation data were fitted well to normal distribution curves and mean plus three times of standard deviation was defined to be a maximum shear stress value. By applying the defined maximum shear stress to a membrane fouling model, trans-membrane pressure curve in the MBR experiment was simulated well by the fouling model indicting that the maximum shear stress, not time-averaged shear stress, can be regarded as an effective shear stress to prevent membrane fouling in submerged flat-sheet MBRs.

  12. Wall shear stress indicators in abnormal aortic geometries

    NASA Astrophysics Data System (ADS)

    Prahl Wittberg, Lisa; van Wyk, Stevin; Fuchs, Laszlo; Gutmark, Ephraim; Gutmark-Little, Iris

    2015-11-01

    Cardiovascular disease, such as atherosclerosis, occurs at specific locations in the arterial tree. Characterizing flow and forces at these locations is crucial to understanding the genesis of disease. Measures such as time average wall shear stress, oscillatory shear index, relative residence time and temporal wall shear stress gradients have been shown to identify plaque prone regions. The present paper examines these indices in three aortic geometries obtained from patients whose aortas are deformed due to a genetic pathology and compared to one normal geometry. This patient group is known to be prone to aortic dissection and our study aims to identify early indicators that will enable timely intervention. Data obtained from cardiac magnetic resonance imaging is used to reconstruct the aortic arch. The local unsteady flow characteristics are calculated, fully resolving the flow field throughout the entire cardiac cycle. The Quemada model is applied to account for the non-Newtonian properties of blood, an empirical model valid for different red blood cell loading. The impact of the deformed aortic geometries is analyzed to identify flow patterns that could lead to arterial disease at certain locations.

  13. Mitochondria-Derived Reactive Oxygen Species Mediate Heme Oxygenase-1 Expression in Sheared Endothelial CellsS⃞

    PubMed Central

    Han, Zhaosheng; Varadharaj, Saradhadevi; Giedt, Randy J.; Zweier, Jay L.; Szeto, Hazel H.; Alevriadou, B. Rita

    2009-01-01

    Bovine aortic endothelial cells (ECs) respond to nitric oxide (NO) donors by activating the redox-sensitive NF-E2-related factor 2/antioxidant response element pathway and up-regulating heme oxygenase (HO)-1 expression. EC exposure to steady laminar shear stress causes a sustained increase in NO, a transient increase in reactive oxygen species (ROS), and activation of the HO-1 gene. Because steady laminar flow increases the mitochondrial superoxide (\\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{O}}_{2}^{\\overline{.}}\\end{equation*}\\end{document}) production, we hypothesized that mitochondria-derived ROS play a role in shear-induced HO-1 expression. Flow (10 dynes/cm2, 6 h)-induced expression of HO-1 protein was abolished when BAECs were preincubated and sheared in the presence of either NG-nitro-l-arginine methyl ester or N-acetyl-l-cysteine, suggesting that either NO or ROS up-regulates HO-1. Ebselen and diphenylene iodonium blocked HO-1 expression, and uric acid had no effect. The mitochondrial electron transport chain inhibitors, myxothiazol, rotenone, or antimycin A, and the mitochondria-targeted antioxidant peptide, Szeto-Schiller (SS)-31, which scavenges \\documentclass[10pt]{article} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{pmc} \\usepackage[Euler]{upgreek} \\pagestyle{empty} \\oddsidemargin -1.0in \\begin{document} \\begin{equation*}{\\mathrm{O}}_{2}^{\\overline{.}}\\end{equation*}\\end{document}, hydrogen peroxide (H2O2), peroxynitrite, and hydroxyl radicals, markedly inhibited the increase in HO-1 expression. These data collectively suggest that mitochondrial H2O2 mediates the HO-1 induction. Mito

  14. Acute restraint stress induces endothelial dysfunction: role of vasoconstrictor prostanoids and oxidative stress.

    PubMed

    Carda, Ana P P; Marchi, Katia C; Rizzi, Elen; Mecawi, André S; Antunes-Rodrigues, José; Padovan, Claudia M; Tirapelli, Carlos R

    2015-01-01

    We hypothesized that acute stress would induce endothelial dysfunction. Male Wistar rats were restrained for 2 h within wire mesh. Functional and biochemical analyses were conducted 24 h after the 2-h period of restraint. Stressed rats showed decreased exploration on the open arms of an elevated-plus maze (EPM) and increased plasma corticosterone concentration. Acute restraint stress did not alter systolic blood pressure, whereas it increased the in vitro contractile response to phenylephrine and serotonin in endothelium-intact rat aortas. NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase, NOS, inhibitor) did not alter the contraction induced by phenylephrine in aortic rings from stressed rats. Tiron, indomethacin and SQ29548 reversed the increase in the contractile response to phenylephrine induced by restraint stress. Increased systemic and vascular oxidative stress was evident in stressed rats. Restraint stress decreased plasma and vascular nitrate/nitrite (NOx) concentration and increased aortic expression of inducible (i) NOS, but not endothelial (e) NOS. Reduced expression of cyclooxygenase (COX)-1, but not COX-2, was observed in aortas from stressed rats. Restraint stress increased thromboxane (TX)B(2) (stable TXA(2) metabolite) concentration but did not affect prostaglandin (PG)F2α concentration in the aorta. Restraint reduced superoxide dismutase (SOD) activity, whereas concentrations of hydrogen peroxide (H(2)O(2)) and reduced glutathione (GSH) were not affected. The major new finding of our study is that restraint stress increases vascular contraction by an endothelium-dependent mechanism that involves increased oxidative stress and the generation of COX-derived vasoconstrictor prostanoids. Such stress-induced endothelial dysfunction could predispose to the development of cardiovascular diseases.

  15. miR-126 Is Involved in Vascular Remodeling under Laminar Shear Stress

    PubMed Central

    Mondadori dos Santos, Ana; Metzinger, Laurent; Haddad, Oualid; M'baya-Moutoula, Eléonore; Taïbi, Fatiha; Charnaux, Nathalie; Massy, Ziad A.; Hlawaty, Hanna; Metzinger-Le Meuth, Valérie

    2015-01-01

    Morphology and changes in gene expression of vascular endothelium are mainly due to shear stress and inflammation. Cell phenotype modulation has been clearly demonstrated to be controlled by small noncoding micro-RNAs (miRNAs). This study focused on the effect of laminar shear stress (LSS) on human endothelial cells (HUVECs), with an emphasis on the role of miRNA-126 (miR-126). Exposure of HUVECs in vitro to LSS modified the shape of HUVECs and concomitantly regulated the expression of miR-126, vascular cell adhesion molecule 1 (VCAM-1), and syndecan-4 (SDC-4). A significant upregulation of miR-126 during long-term exposure to flow was shown. Interestingly, LSS enhanced SDC-4 expression on the HUVEC membranes. Overexpression of miR-126 in HUVECs decreased the levels of targets stromal cell-derived factor-1 SDF-1/CXCL12 and VCAM-1 but increased the expression of RGS16, CXCR4, and SDC-4. No significant difference in terms of cell proliferation and apoptosis was observed between scramble, anti-miR-126, and pre-miR-126 transfected HUVECs. In Apo-E KO/CKD mice aortas expressing a high level of miR-126, SDC-4 was concomitantly increased. In conclusion, our results suggest that miR-126 (i) is overexpressed by long-term LSS, (ii) has a role in up- and downregulation of genes involved in atherosclerosis, and (iii) affects SDC-4 expression. PMID:26221595

  16. A method for measurement of turbulent wall shear stress

    NASA Astrophysics Data System (ADS)

    Wagner, Peter M.; Leehey, Patrick

    A cylinder is placed near the wall in the viscous sublayer of a turbulent boundary layer. It is suspended torsionally about its axis. The axis is parallel to the wall and transverse to the mean flow direction. The torque on the cylinder is proportional to the shear stress of the fluid on the wall below. In principle the torque is insensitive to the blockage effect of the cylinder. The device has been tested in a laminar shear flow created in a cone-and-plate apparatus. It shows a long range of linear response. There is no evidence of hysteresis upon flow reversal. Plans for dynamic testing in a turbulent oil channel flow and the applicability of micro-machining techniques from silicon technololgy to the further miniaturization of this gauge are discussed.

  17. Role of CD11/CD18 in shear rate-dependent leukocyte-endothelial cell interactions in cat mesenteric venules.

    PubMed Central

    Perry, M A; Granger, D N

    1991-01-01

    In vivo microscopy was used to assess the relationships among shear rate (and shear stress), leukocyte rolling velocity, and leukocyte adherence in a cat mesentery preparation. Shear rate in individual venules and arterioles of 25-35 microns diameter were varied over a wide range by graded occlusion of an arterial loop. There was a linear decline in leukocyte rolling velocity (Vwbc) as red cell velocity (Vrbc) was reduced. The ratio Vwbc/Vrbc remained constant despite variations in shear stress from 5-25 dyn/cm2. A reduction in shear stress was associated with an increased leukocyte adherence, particularly when Vwbc was reduced below 50 microns/s. Reduction in wall shear rate below 500 s-1 in arterioles allowed 1-3 leukocytes to adhere per 100 microns length of vessel, while venules exposed to the same shear rates had 5-16 adherent leukocytes. In arterioles, leukocyte rolling was only observed at low shear rates. At shear rates less than 250 s-1 leukocyte rolling velocity was faster in arterioles than venules, and the ratio Vwbc/Vrbc for arterioles was 0.08 +/- 0.02, which was fourfold higher than the ratio obtained in venules at similar shear rates. Pretreatment with the CD18-specific antibody (mAb) IB4 increased leukocyte rolling velocity in venules by approximately 20 microns/s at red cell velocities below 2,000 microns/s. mAb IB4 largely prevented the leukocyte adherence to arterioles and venules, and increased the ratio Vwbc/Vrbc observed in venules at low shear elicit a CD18-dependent adhesive interaction between leukocytes and microvascular endothelium, and that differences in shear rates cannot explain the greater propensity for leukocyte rolling and adhesion in venules than arterioles. PMID:1673690

  18. Liposome clusters with shear stress-induced membrane permeability.

    PubMed

    Yoshimoto, Makoto; Tamura, Ryota; Natsume, Tomotaka

    2013-09-01

    Clusters of negatively charged liposomes were prepared by the addition of Ca(2+) and characterized in their structure and membrane permeability under shear stress. The liposomes mainly used were composed of zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 20 mol% negatively charged 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and 30 mol% cholesterol. The liposomes with mean diameter of 193 nm were aggregated into the clusters with a distribution peak at about 1.5 μm in the 50mM Tris buffer solution of pH 8.5 at the lipid and Ca(2+) concentrations of 1.0mM and 40 mM, respectively. More than 90% of liposomes were redispersed at the Ca(2+) concentration of 80 mM. POPG-rich liposomes (POPC/POPG/cholesterol=5:65:30 [lipid]=1.0mM) were irreversibly aggregated at [Ca(2+)]≥ 10 mM, indicating the significant contribution of POPC to the reversible clustering of liposomes. The membranes of liposome clusters were impermeable to 5(6)-carboxyfluorescein (CF) in the static liquid system at 25°C due to the decrease in specific surface area of the liposomal system. In the shear flow, in clear contrast, continuous membrane permeation of CF was observed at the shear rate of 1.5 × 10(3)s(-1), exhibiting comparable membrane permeability to the non-clustered liposomes. The theoretical analysis of modified DLVO potential indicated that liposome membranes were not in contact with each other within the clusters. Therefore, the liposome clusters are structurally flexible under the applied shear stress, providing sufficient lipid membrane-water interfacial area for the permeation of CF. The results obtained would be important to control the formation of liposome clusters and their permeabilization for biochemical and biomedical applications.

  19. Endothelial dysfunction and preeclampsia: role of oxidative stress

    PubMed Central

    Sánchez-Aranguren, Lissette C.; Prada, Carlos E.; Riaño-Medina, Carlos E.; Lopez, Marcos

    2014-01-01

    Preeclampsia (PE) is an often fatal pathology characterized by hypertension and proteinuria at the 20th week of gestation that affects 5–10% of the pregnancies. The problem is particularly important in developing countries in where the incidence of hypertensive disorders of pregnancy is higher and maternal mortality rates are 20 times higher than those reported in developed countries. Risk factors for the development of PE include obesity, insulin resistance and hyperlipidemia that stimulate inflammatory cytokine release and oxidative stress leading to endothelial dysfunction (ED). However, how all these clinical manifestations concur to develop PE is still not very well understood. The related poor trophoblast invasion and uteroplacental artery remodeling described in PE, increases reactive oxygen species (ROS), hypoxia and ED. Here we aim to review current literature from research showing the interplay between oxidative stress, ED and PE to the outcomes of current clinical trials aiming to prevent PE with antioxidant supplementation. PMID:25346691

  20. The release of shear stress in metals under dynamic loading

    NASA Astrophysics Data System (ADS)

    Vignjevic, Rade; Bourne, Neil

    2013-06-01

    Metals under shock loading relieve shear stress by slip after. This work focuses on the types of loading where a metal initially responds entirely elastically and plasticity with deformation mechanisms developing over time and determined by the material's state and microstructure. Finite kinetics in shock is mirrored in several commonly observed responses including elastic precursor decay and the measurement of shear stress histories during load. FCC and BCC metals have different kinetics, with those of BCC metals slower. A model, under development, is implemented here to depict the behaviour observed by assigning a finite time to the return of the state point from the quasi equilibrium yield surface to the equilibrium yield surface. This delays the softening of the material and reproduces observed response in the weak shock regime. The model is based on the assumption that formation and self-organisation of dislocation structures at various scales maximises dissipation rate (minimize the free energy) in the material. Initial validation of the model is performed on tantalum by comparing stress histories under shock and shock-less loading with experimental data in order to assess its ability to reproduce experimentally observed features.

  1. Experimental Stress Analysis of Stiffened Cylinders with Cutouts : Shear Load

    NASA Technical Reports Server (NTRS)

    Rosecrans, Richard; Schlechte , Floyd R

    1954-01-01

    A cylindrical semimonocoque shell of circular cross section was mounted as a cantilever and loaded by a direct shear at the tip. The cylinder was tested with no cutout, with a rectangular cutout on the tension side, and with the cutout centered on the neutral axis on one side of the cylinder. The cutout was successively enlarged through six sizes varying from 30 degrees to 130 degrees in circumference and from 1 and 2 bays in length. Strain measurements were made with resistance-type wire strain gages near the cutout on the stringers, the skin, and the rings for each case, and the stresses obtained are presented in tables. (author)

  2. Role of fluid shear stress in regulating VWF structure, function and related blood disorders

    PubMed Central

    Gogia, Shobhit; Neelamegham, Sriram

    2015-01-01

    Von Willebrand factor (VWF) is the largest glycoprotein in blood. It plays a crucial role in primary hemostasis via its binding interaction with platelet and endothelial cell surface receptors, other blood proteins and extra-cellular matrix components. This protein is found as a series of repeat units that are disulfide bonded to form multimeric structures. Once in blood, the protein multimer distribution is dynamically regulated by fluid shear stress which has two opposing effects: it promotes the aggregation or self-association of multiple VWF units, and it simultaneously reduces multimer size by facilitating the force-dependent cleavage of the protein by various proteases, most notably ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type repeats, motif 1 type 13). In addition to these effects, fluid shear also controls the solution and substrate-immobilized structure of VWF, the nature of contact between blood platelets and substrates, and the biomechanics of the GpIbα–VWF bond. These features together regulate different physiological and pathological processes including normal hemostasis, arterial and venous thrombosis, von Willebrand disease, thrombotic thrombocytopenic purpura and acquired von Willebrand syndrome. This article discusses current knowledge of VWF structure–function relationships with emphasis on the effects of hydrodynamic shear, including rapid methods to estimate the nature and magnitude of these forces in selected conditions. It shows that observations made by many investigators using solution and substrate-based shearing devices can be reconciled upon considering the physical size of VWF and the applied mechanical force in these different geometries. PMID:26600266

  3. Obesity-induced Endoplasmic Reticulum Stress Causes Lung Endothelial Dysfunction and Promotes Acute Lung Injury.

    PubMed

    Shah, Dilip; Romero, Freddy; Guo, Zhi; Sun, Jianxin; Li, Jonathan; Kallen, Caleb B; Naik, Ulhas P; Summer, Ross

    2017-03-09

    Obesity is a significant risk factor for the acute respiratory distress syndrome (ARDS). The mechanisms underlying this association are unknown. We recently showed that diet-induced obese (DIO) mice exhibit pulmonary vascular endothelial dysfunction which is associated with enhanced susceptibility to lipopolysaccharide (LPS)-induced lung injury. Here, we demonstrate that lung endothelial dysfunction in DIO mice coincides with increased endoplasmic reticulum (ER) stress. Specifically, we observed enhanced expression of the major sensors of misfolded proteins including PERK, IREα and ATF6, in whole lung and in lung endothelial cells isolated from DIO mice. Further, we found that lung endothelial cells exposed to serum from obese mice, or to saturated fatty acids that mimic obese serum, resulted in enhanced expression of markers of ER stress and the induction of other biological responses that typify the lung endothelium of DIO mice. Similar changes were observed in lung endothelial cells and in whole lung tissue after exposure to tunicamycin, a compound that causes ER stress by blocking N-linked glycosylation; indicating that ER stress causes endothelial dysfunction in the lung. Treatment with 4-PBA, a chemical protein chaperone that reduces ER stress, restored vascular endothelial cell expression of adhesion molecules and protected against LPS-induced acute lung injury in DIO mice. Our work indicates that fatty acids in obese serum induce ER stress in the pulmonary endothelium leading to pulmonary endothelial cell dysfunction. Our work suggests that reducing protein load in the endoplasmic reticulum of pulmonary endothelial cells might protect against ARDS in obese individuals.

  4. Interfacial shear stress in stratified flow in a horizontal rectangular duct

    SciTech Connect

    Lorencez, C.; Kawaji, M.; Murao, Y.

    1995-09-01

    Interfacial shear stress has been experimentally examined for both cocurrent and countercurrent stratified wavy flows in a horizontal interfacial shear stress from the measurements were examined and the results have been compared with existing correlations. Some differences were found in the estimated interfacial shear stress from the measurements were examined and the results have been compared with existing correlations. Some differences were found in the estimated interfacial shear stress values at high gas flow rates which could be attributed to the assumptions and procedures involved in each method. The interfacial waves and secondary motions were also found to have significant effects on the accuracy of Reynolds stress and turbulence kinetic energy extrapolation methods.

  5. Shear Stress, Energy Losses, and Costs: A Resolved Dilemma of Pulsatile Cardiac Assist Devices

    PubMed Central

    Liu, Jia; Dai, Gang; Carbognani, Daniel; Yang, Daya; Wu, Guifu; Wang, Qinmei; Chachques, Juan Carlos

    2014-01-01

    Cardiac assist devices (CAD) cause endothelial dysfunction with considerable morbidity. Employment of pulsatile CAD remains controversial due to inadequate perfusion curves and costs. Alternatively, we are proposing a new concept of pulsatile CAD based on a fundamental revision of the entire circulatory system in correspondence with the physiopathology and law of physics. It concerns a double lumen disposable tube device that could be adapted to conventional cardiopulmonary bypass (CPB) and/or CAD, for inducing a homogenous, downstream pulsatile perfusion mode with lower energy losses. In this study, the device's prototypes were tested in a simulated conventional pediatric CPB circuit for energy losses and as a left ventricular assist device (LVAD) in ischemic piglets model for endothelial shear stress (ESS) evaluations. In conclusion and according to the study results the pulsatile tube was successfully capable of transforming a conventional CPB and/or CAD steady flow into a pulsatile perfusion mode, with nearly physiologic pulse pressure and lower energy losses. This represents a cost-effective promising method with low mortality and morbidity, especially in fragile cardiac patients. PMID:24511541

  6. A review of Reynolds stress models for turbulent shear flows

    NASA Technical Reports Server (NTRS)

    Speziale, Charles G.

    1995-01-01

    A detailed review of recent developments in Reynolds stress modeling for incompressible turbulent shear flows is provided. The mathematical foundations of both two-equation models and full second-order closures are explored in depth. It is shown how these models can be systematically derived for two-dimensional mean turbulent flows that are close to equilibrium. A variety of examples are provided to demonstrate how well properly calibrated versions of these models perform for such flows. However, substantial problems remain for the description of more complex turbulent flows where there are large departures from equilibrium. Recent efforts to extend Reynolds stress models to nonequilibrium turbulent flows are discussed briefly along with the major modeling issues relevant to practical naval hydrodynamics applications.

  7. Shear stress paradigm for perinatal fractal arterial network remodeling in lambs with pulmonary hypertension and increased pulmonary blood flow.

    PubMed

    Ghorishi, Zahra; Milstein, Jay M; Poulain, Francis R; Moon-Grady, Anita; Tacy, Theresa; Bennett, Stephen H; Fineman, Jeffery R; Eldridge, Marlowe W

    2007-06-01

    Congenital heart disease with increased blood flow commonly leads to the development of increased pulmonary vascular reactivity and pulmonary arterial hypertension by mechanisms that remain unclear. We hypothesized a shear stress paradigm of hemodynamic reactivity and network remodeling via the persistence and/or exacerbation of a fetal diameter bifurcation phenotype [parent diameter d(0) and daughters d(1) >or= d(2) with alpha < 2 in (d(1)/d(0))(alpha) + (d(2)/d(0))(alpha) and area ratio beta < 1 in beta = (d(1)(2)+ d(2)(2))/ d(0)(2)] that mechanically acts as a high resistance magnifier/shear stress amplifier to blood flow. Evidence of a hemodynamic influence on network remodeling was assessed with a lamb model of high-flow-induced secondary pulmonary hypertension in which an aortopulmonary graft was surgically placed in one twin in utero (Shunt twin) but not in the other (Control twin). Eight weeks after birth arterial casts were made of the left pulmonary arterial circulation. Bifurcation diameter measurements down to 0.010 mm in the Shunt and Control twins were then compared with those of an unoperated fetal cast. Network organization, cumulative resistance, and pressure/shear stress distributions were evaluated via a fractal model whose dimension D(0) approximately alpha delineates hemodynamic reactivity. Fetus and Control twin D(0) differed: fetus D(0)=1.72, a high-resistance/shear stress amplifying condition; control twin D(0) = 2.02, an area-preserving transport configuration. The Shunt twin (D(0)=1.72) maintained a fetal design but paradoxically remodeled diameter geometry to decrease cumulative resistance relative to the Control twin. Our results indicate that fetal/neonatal pulmonary hemodynamic reactivity remodels in response to shear stress, but the response to elevated blood flow and pulmonary hypertension involves the persistence and exacerbation of a fetal diameter bifurcation phenotype that facilitates endothelial dysfunction/injury.

  8. Mass Transport and Shear Stress in the Carotid Artery Bifurcation

    NASA Astrophysics Data System (ADS)

    Gorder, Riley; Aliseda, Alberto

    2010-11-01

    The carotid artery bifurcation (CAB) is one of the leading sites for atherosclerosis, a major cause of death and disability in the developed world. The specific processes by which the complex flow found at the bifurcation and carotid sinus promotes plaque formation and growth are not fully understood. Shear stress, mass transport, and flow residence times are considered key factors. Although the governing equations closely link shear stress and mass transfer, the pulsatile, transitional, and detached flow found at the CAB can lead to differences between regions of WSS and mass transfer statistics. In this study, CAB geometries are reconstructed from patient specific 3D ultrasound medical imaging. Using ANSYS FLUENT, the fluid flow and scalar transport was solved using realistic flow conditions and various mass transfer boundary conditions. The spatial and temporal resolution was validated against the analytical solution of the Graetz-Nusselt problem with constant wall flux to ensure the scalar transport is resolved for a Peclet number up to 100,000. High residence time regions are investigated by determining the number of cardiac cycles required to flush out the carotid sinus. The correlations between regions of low WSS, high OSI, and scalar concentration are computed and interpreted in the context of atherosclerotic plaque origin and progression.

  9. Complete Release of Horizontal Shear Stresses During Geothermal Reservoir Stimulation

    NASA Astrophysics Data System (ADS)

    Schoenball, M.; Gaucher, E.; Wellmann, F.; Kohl, T.

    2013-12-01

    Seismicity can be induced in previously seismically inactive regions by man-made changes of the stress field. Notable stress perturbations are created by injection or withdrawal of fluids such as wastewater, fresh water or hydrocarbons. Over the last decades our knowledge of the physical processes of induced seismicity has improved largely. However, the driving force of seismicity, i.e. the actual perturbation of the stress field in the reservoir during fluid injection, remains largely unknown up to now. Measurements of fluid pressure at the well are not enough to extrapolate the pressure change in the reservoir. Here we study the evolution of the stress field during a massive hydraulic stimulation of a 5 km deep well at the enhanced geothermal system at Soultz-sous-Forêts, France. Fresh water was pumped with rates of 30 to 50 ls-1 for 6 days. Locations of 7215 events with maximum magnitude of MW=2.5 were obtained, for 715 events with MW > 1 focal mechanism solutions were derived. At first we present observations of several peculiar phenomena of the seismicity migration, of fluid flow and earthquake mechanisms following the shut-in of the well, which indicate to yet not understood hydro-mechanical coupling mechanisms in connection with shut-in. In order to analyze the changes of the stress field during and after the stimulation we identify the fracture planes from the two nodal planes by a probability-based method where we incorporate structural geological information gained from well logs and uncertainties of the determination of focal mechanism solutions and independent estimates of the stress field. In principle, this approach is able to incorporate further uncertainties, if available. We then conduct stress inversions resolved in time and depth to study spatio-temporal changes of the stress tensor. Our results show an increasingly perturbed stress state with time with a strong reduction of the horizontal shear stresses in areas of highest seismic activity

  10. Viscosity, Shear Waves, and Atomic-Level Stress-Stress Correlations

    NASA Astrophysics Data System (ADS)

    Levashov, V. A.; Morris, J. R.; Egami, T.

    2011-03-01

    The Green-Kubo equation relates the macroscopic stress-stress correlation function to a liquid’s viscosity. The concept of the atomic-level stresses allows the macroscopic stress-stress correlation function in the equation to be expressed in terms of the space-time correlations among the atomic-level stresses. Molecular dynamics studies show surprisingly long spatial extension of stress-stress correlations and also longitudinal and transverse waves propagating in liquids over ranges which could exceed the system size. The results reveal that the range of propagation of shear waves corresponds to the range of distances relevant for viscosity. Thus our results show that viscosity is a fundamentally nonlocal quantity. We also show that the periodic boundary conditions play a nontrivial role in molecular dynamics simulations, effectively masking the long-range nature of viscosity.

  11. Quantifying turbulent wall shear stress in a stenosed pipe using large eddy simulation.

    PubMed

    Gårdhagen, Roland; Lantz, Jonas; Carlsson, Fredrik; Karlsson, Matts

    2010-06-01

    Large eddy simulation was applied for flow of Re=2000 in a stenosed pipe in order to undertake a thorough investigation of the wall shear stress (WSS) in turbulent flow. A decomposition of the WSS into time averaged and fluctuating components is proposed. It was concluded that a scale resolving technique is required to completely describe the WSS pattern in a subject specific vessel model, since the poststenotic region was dominated by large axial and circumferential fluctuations. Three poststenotic regions of different WSS characteristics were identified. The recirculation zone was subject to a time averaged WSS in the retrograde direction and large fluctuations. After reattachment there was an antegrade shear and smaller fluctuations than in the recirculation zone. At the reattachment the fluctuations were the largest, but no direction dominated over time. Due to symmetry the circumferential time average was always zero. Thus, in a blood vessel, the axial fluctuations would affect endothelial cells in a stretched state, whereas the circumferential fluctuations would act in a relaxed direction.

  12. Cell-free layer and wall shear stress variation in microvessels.

    PubMed

    Yin, Xuewen; Zhang, Junfeng

    2012-01-01

    In this study, we simulated multiple red blood cells flowing through straight microvessels with the immersed-boundary lattice-Boltzmann model to examine the shear stress variation on the microvessel surface and its relation to the properties of cell-free layer. Significant variation in shear stress has been observed due to the irregular configuration of blood cells flowing near the microvessel wall. A low shear stress is typically found at locations where there is a cell flowing close to the wall, and a large shear stress at locations with a relatively wide gap between cell and wall. This relationship between the shear stress magnitude and the distance between cell and wall has been attributed to the reverse pressure difference developed between the front and rear sides of a cell flowing near the vessel wall. We further studied the effects of several hemodynamic factors on the variation of shear stress, including the cell deformability, the flow rate, and the aggregation among red blood cells. These simulations show that the shear stress variation is less profound in situations with wider cell-free layers, since the reverse pressure difference around the edge cells is less evident, and the influence of this pressure difference on wall shear stress becomes weaker. This study also demonstrates the complexity of the flow field in the gap between cell and wall. More precise experimental techniques are required accurately measure such shear stress variation in microcirculation.

  13. High Shear Stresses under Exercise Condition Destroy Circulating Tumor Cells in a Microfluidic System

    PubMed Central

    Regmi, Sagar; Fu, Afu; Luo, Kathy Qian

    2017-01-01

    Circulating tumor cells (CTCs) are the primary targets of cancer treatment as they cause distal metastasis. However, how CTCs response to exercise-induced high shear stress is largely unknown. To study the effects of hemodynamic microenvironment on CTCs, we designed a microfluidic circulatory system that produces exercise relevant shear stresses. We explore the effects of shear stresses on breast cancer cells with different metastatic abilities, cancer cells of ovarian, lung and leukemic origin. Three major findings were obtained. 1) High shear stress of 60 dynes/cm2 achievable during intensive exercise killed more CTCs than low shear stress of 15 dynes/cm2 present in human arteries at the resting state. 2) High shear stress caused necrosis in over 90% of CTCs within the first 4 h of circulation. More importantly, the CTCs that survived the first 4 h-circulation, underwent apoptosis during 16–24 h of post-circulation incubation. 3) Prolonged high shear stress treatment effectively reduced the viability of highly metastatic and drug resistant breast cancer cells. As high shear stress had much less damaging effects on leukemic cells mimicking the white blood cells, we propose that intensive exercise may be a good strategy for generating high shear stress that can destroy CTCs and prevent cancer metastasis. PMID:28054593

  14. A Single Parameter to Characterize Wall Shear Stress Developed from an Underexpanded Axisymmetric Impinging Jet

    NASA Astrophysics Data System (ADS)

    Fillingham, Patrick; Murali, Harikrishnan

    2016-11-01

    Wall shear stress is characterized for underexpanded axisymmetric impinging jets for the application of aerodynamic particle resuspension from a surface. Analysis of the flow field and the wall shear stress resulted from normally impinging axisymmetric jets is conducted using Computational Fluid Dynamics. A normally impinging jet is modeled with a constant area nozzle, while varying height to diameter ratio (H/D) and inlet pressures. Schlieren photography is used to visualize the density gradient of the flow field for validation of the CFD. The Dimensionless Jet Parameter (DJP) is developed to describe flow regimes and characterize the shear stress. The DJP is defined as being proportional to the jet pressure ratio divided by the H/D ratio squared. Maximum wall shear stress is examined as a function of DJP with three distinct regimes: (i) subsonic impingement (DJP<1), (ii) transitional (12). Due to the jet energy dissipation in shock structures, which become a dominant dissipation mechanism in the supersonic impingement regime, wall shear stress is limited to a finite value. Additionally, formation of shock structures in the wall flow were observed for DJP>2 resulting in difficulties with dimensionless analysis. In the subsonic impingement and transitional regimes equations as a function of the DJP are obtained for the maximum wall shear stress magnitude, maximum shear stress location, and shear stress decay. Using these relationships wall shear stress can be predicted at all locations along the impingement surface.

  15. Shear Stress-Normal Stress (Pressure) Ratio Decides Forming Callus in Patients with Diabetic Neuropathy.

    PubMed

    Amemiya, Ayumi; Noguchi, Hiroshi; Oe, Makoto; Takehara, Kimie; Ohashi, Yumiko; Suzuki, Ryo; Yamauchi, Toshimasa; Kadowaki, Takashi; Sanada, Hiromi; Mori, Taketoshi

    2016-01-01

    Aim. Callus is a risk factor, leading to severe diabetic foot ulcer; thus, prevention of callus formation is important. However, normal stress (pressure) and shear stress associated with callus have not been clarified. Additionally, as new valuables, a shear stress-normal stress (pressure) ratio (SPR) was examined. The purpose was to clarify the external force associated with callus formation in patients with diabetic neuropathy. Methods. The external force of the 1st, 2nd, and 5th metatarsal head (MTH) as callus predilection regions was measured. The SPR was calculated by dividing shear stress by normal stress (pressure), concretely, peak values (SPR-p) and time integral values (SPR-i). The optimal cut-off point was determined. Results. Callus formation region of the 1st and 2nd MTH had high SPR-i rather than noncallus formation region. The cut-off value of the 1st MTH was 0.60 and the 2nd MTH was 0.50. For the 5th MTH, variables pertaining to the external forces could not be determined to be indicators of callus formation because of low accuracy. Conclusions. The callus formation cut-off values of the 1st and 2nd MTH were clarified. In the future, it will be necessary to confirm the effect of using appropriate footwear and gait training on lowering SPR-i.

  16. Analysis of bonded joints. [shear stress and stress-strain diagrams

    NASA Technical Reports Server (NTRS)

    Srinivas, S.

    1975-01-01

    A refined elastic analysis of bonded joints which accounts for transverse shear deformation and transverse normal stress was developed to obtain the stresses and displacements in the adherends and in the bond. The displacements were expanded in terms of polynomials in the thicknesswise coordinate; the coefficients of these polynomials were functions of the axial coordinate. The stress distribution was obtained in terms of these coefficients by using strain-displacement and stress-strain relations. The governing differential equations were obtained by integrating the equations of equilibrium, and were solved. The boundary conditions (interface or support) were satisfied to complete the analysis. Single-lap, flush, and double-lap joints were analyzed, along with the effects of adhesive properties, plate thicknesses, material properties, and plate taper on maximum peel and shear stresses in the bond. The results obtained by using the thin-beam analysis available in the literature were compared with the results obtained by using the refined analysis. In general, thin-beam analysis yielded reasonably accurate results, but in certain cases the errors were high. Numerical investigations showed that the maximum peel and shear stresses in the bond can be reduced by (1) using a combination of flexible and stiff bonds, (2) using stiffer lap plates, and (3) tapering the plates.

  17. Shear Stress-Normal Stress (Pressure) Ratio Decides Forming Callus in Patients with Diabetic Neuropathy

    PubMed Central

    Noguchi, Hiroshi; Takehara, Kimie; Ohashi, Yumiko; Suzuki, Ryo; Yamauchi, Toshimasa; Kadowaki, Takashi; Sanada, Hiromi

    2016-01-01

    Aim. Callus is a risk factor, leading to severe diabetic foot ulcer; thus, prevention of callus formation is important. However, normal stress (pressure) and shear stress associated with callus have not been clarified. Additionally, as new valuables, a shear stress-normal stress (pressure) ratio (SPR) was examined. The purpose was to clarify the external force associated with callus formation in patients with diabetic neuropathy. Methods. The external force of the 1st, 2nd, and 5th metatarsal head (MTH) as callus predilection regions was measured. The SPR was calculated by dividing shear stress by normal stress (pressure), concretely, peak values (SPR-p) and time integral values (SPR-i). The optimal cut-off point was determined. Results. Callus formation region of the 1st and 2nd MTH had high SPR-i rather than noncallus formation region. The cut-off value of the 1st MTH was 0.60 and the 2nd MTH was 0.50. For the 5th MTH, variables pertaining to the external forces could not be determined to be indicators of callus formation because of low accuracy. Conclusions. The callus formation cut-off values of the 1st and 2nd MTH were clarified. In the future, it will be necessary to confirm the effect of using appropriate footwear and gait training on lowering SPR-i. PMID:28050567

  18. Sirtuin1 protects endothelial Caveolin-1 expression and preserves endothelial function via suppressing miR-204 and endoplasmic reticulum stress

    PubMed Central

    Kassan, M.; Vikram, A.; Kim, Y. R.; Li, Q.; Kassan, A.; Patel, H. H.; Kumar, S.; Gabani, M.; Liu, J.; Jacobs, J. S.; Irani, K.

    2017-01-01

    Sirtuin1 (Sirt1) is a class III histone deacetylase that regulates a variety of physiological processes, including endothelial function. Caveolin1 (Cav1) is also an important determinant of endothelial function. We asked if Sirt1 governs endothelial Cav1 and endothelial function by regulating miR-204 expression and endoplasmic reticulum (ER) stress. Knockdown of Sirt1 in endothelial cells, and in vivo deletion of endothelial Sirt1, induced endothelial ER stress and miR-204 expression, reduced Cav1, and impaired endothelium-dependent vasorelaxation. All of these effects were reversed by a miR-204 inhibitor (miR-204 I) or with overexpression of Cav1. A miR-204 mimic (miR-204 M) decreased Cav1 in endothelial cells. In addition, high-fat diet (HFD) feeding induced vascular miR-204 and reduced endothelial Cav1. MiR-204-I protected against HFD-induced downregulation of endothelial Cav1. Moreover, pharmacologic induction of ER stress with tunicamycin downregulated endothelial Cav1 and impaired endothelium-dependent vasorelaxation that was rescued by overexpressing Cav1. In conclusion, Sirt1 preserves Cav1-dependent endothelial function by mitigating miR-204-mediated vascular ER stress. PMID:28181559

  19. Healing and Shear Stress Reduction on Single Fracture of Rock Salt and Limestone under Slide-Hold-Slide Direct Shear Condition

    NASA Astrophysics Data System (ADS)

    Kishida, K.; Yano, T.; Yasuhara, H.

    2012-12-01

    In order to clarify the influence of the holding state on the shear strength in the shear process of a single rock fracture, slide-hold-slide (SHS) direct shear-flow coupling tests were carried out on single rock fractures at several confining stresses and under saturated/unsaturated conditions (Kishida, et al., 2011). Consequently, the mortar specimen could be confirmed as the significant shear strength recovery on the SHS process. In this research, the SHS direct shear tests are carried out on the halite (rock salt) and the limestone. In the case of rock salt, a single tensile fracture is artificially created by cutting away. On the other hand, the limestone has a natural rock joint. The experiments are carried out under various normal confining stress conditions and are employed various holding period at the residual state. Figure 1 shows the shear stress - shear displacement of the SHS direct shear experiments on the rock salt. From all cases, the shear stress increases at the initial phase of the experiments, and then, the shear stress reaches at the peak shear strength. After that, the shear stress slightly decreases such as strain softening. Finally, the shear stress reaches to the residual stress state. In every SHS processes, the shear stress is reducing in various hold period. And then, the shear stress is increasing in the process of re-sliding. The shear stress in the process of re-sliding takes over the value at the start time of the holding process. The shear stress reaches at the peak, and then, it reaches the residual stress state. In all cases, as the holding period becomes longer, it is confirmed that the decrement of the shear stress in the holding process is increasing and the increment of the shear stress at the re-sliding process is increasing. Therefore, it is confirmed that the time dependence of shear strength recovery can be observed. In addition, Dieterich's A constant value for the regression lines (Dieterich, 1972, 1994) is plotted

  20. Interlaminar shear stress effects on the postbuckling response of graphite-epoxy panels

    NASA Technical Reports Server (NTRS)

    Engelstad, S. P.; Knight, N. F., Jr.; Reddy, J. N.

    1990-01-01

    The influence of shear flexibility on overall postbuckling response was assessed, and transverse shear stress distributions in relation to panel failure were examined. Nonlinear postbuckling results are obtained for finite element models based on classical laminated plate theory and first-order shear deformation theory. Good correlation between test and analysis is obtained. The results presented analytically substantiate the experimentally observed failure mode.

  1. Duration of exposure to high fluid shear stress is critical in shear-induced platelet activation-aggregation.

    PubMed

    Zhang, Jian-ning; Bergeron, Angela L; Yu, Qinghua; Sun, Carol; McBride, Latresha; Bray, Paul F; Dong, Jing-fei

    2003-10-01

    Platelet functions are increasingly measured under flow conditions to account for blood hydrodynamic effects. Typically, these studies involve exposing platelets to high shear stress for periods significantly longer than would occur in vivo. In the current study, we demonstrate that the platelet response to high shear depends on the duration of shear exposure. In response to a 100 dyn/cm2 shear stress for periods less than 10-20 sec, platelets in PRP or washed platelets were aggregated, but minimally activated as demonstrated by P-selectin expression and binding of the activation-dependent alphaIIbbeta3 antibody PAC-1 to sheared platelets. Furthermore, platelet aggregation under such short pulses of high shear was subjected to rapid disaggregation. The disaggregated platelets could be re-aggregated by ADP in a pattern similar to unsheared platelets. In comparison, platelets that are exposed to high shear for longer than 20 sec are activated and aggregated irreversibly. In contrast, platelet activation and aggregation were significantly greater in whole blood with significantly less disaggregation. The enhancement is likely via increased collision frequency of platelet-platelet interaction and duration of platelet-platelet association due to high cell density. It may also be attributed to the ADP release from other cells such as red blood cells because increased platelet aggregation in whole blood was partially inhibited by ADP blockage. These studies demonstrate that platelets have a higher threshold for shear stress than previously believed. In a pathologically relevant timeframe, high shear alone is likely to be insufficient in inducing platelet activation and aggregation, but acts synergistically with other stimuli.

  2. Flow Instability and Wall Shear Stress Ocillation in Intracranial Aneurysms

    NASA Astrophysics Data System (ADS)

    Baek, Hyoungsu; Jayamaran, Mahesh; Richardson, Peter; Karniadakis, George

    2009-11-01

    We investigate the flow dynamics and oscillatory behavior of wall shear stress (WSS) vectors in intracranial aneurysms using high-order spectral/hp simulations. We analyze four patient- specific internal carotid arteries laden with aneurysms of different characteristics : a wide-necked saccular aneurysm, a hemisphere-shaped aneurysm, a narrower-necked saccular aneurysm, and a case with two adjacent saccular aneurysms. Simulations show that the pulsatile flow in aneurysms may be subject to a hydrodynamic instability during the decelerating systolic phase resulting in a high-frequency oscillation in the range of 30-50 Hz. When the aneurysmal flow becomes unstable, both the magnitude and the directions of WSS vectors fluctuate. In particular, the WSS vectors around the flow impingement region exhibit significant spatial and temporal changes in direction as well as in magnitude.

  3. Wrinkling Phenomena of Thin Flat Plates Subjected to Shear Stresses

    NASA Technical Reports Server (NTRS)

    Bollenrath, F

    1931-01-01

    This report covers a series of tests on thin flat elastic strips restrained at two parallel edges and subjected to shear by conversely directed stresses. Theoretical treatments, particularly those of Lilly, Southwell and Skan, and Timoshenko are briefly outlined. The problem to be solved by these tests was to find out whether, and to what extent the conditions and assumptions upon which the calculations are based are complied with in the tests. Three materials were used: celluloid, duralumin, brass. Owing to the high elastic deformability of celluloid, it was not only possible to observe the beginning but also to ascertain the type of deflection. The test data on celluloid was affirmed by the experiments with duralumin and brass.

  4. Discovery of shear- and side-specific mRNAs and miRNAs in human aortic valvular endothelial cells

    PubMed Central

    Holliday, Casey J.; Ankeny, Randall F.; Nerem, Robert M.

    2011-01-01

    The role of endothelial cells (ECs) in aortic valve (AV) disease remains relatively unknown; however, disease preferentially occurs in the fibrosa. We hypothesized oscillatory shear (OS) present on the fibrosa stimulates ECs to modify mRNAs and microRNAs (miRNAs) inducing disease. Our goal was to identify mRNAs and miRNAs differentially regulated by OS and laminar shear (LS) in human AVECs (HAVECs) from the fibrosa (fHAVECs) and ventricularis (vHAVECs). HAVECs expressed EC markers as well as some smooth muscle cell markers and functionally aligned with the flow. HAVECs were exposed to OS and LS for 24 h, and total RNA was analyzed by mRNA and miRNA microarrays. We found over 700 and 300 mRNAs down- and upregulated, respectively, by OS; however, there was no side dependency. mRNA microarray results were validated for 26 of 28 tested genes. Ingenuity Pathway Analysis revealed thrombospondin 1 (Thbs1) and NF-κB inhibitor-α (Nfkbia) as highly connected, shear-sensitive genes. miRNA array analysis yielded 30 shear-sensitive miRNAs and 3 side-specific miRNAs. miRNA validation confirmed 4 of 17 shear-sensitive miRNAs and 1 of 3 side-dependent miRNAs. Using miRWalk and several filtering steps, we identified shear-sensitive mRNAs potentially targeted by shear-sensitive miRNAs. These genes and signaling pathways could act as therapeutic targets of AV disease. PMID:21705672

  5. Endothelial Plasticity: Shifting Phenotypes through Force Feedback

    PubMed Central

    Krenning, Guido; Barauna, Valerio G.; Krieger, José E.; Harmsen, Martin C.; Moonen, Jan-Renier A. J.

    2016-01-01

    The endothelial lining of the vasculature is exposed to a large variety of biochemical and hemodynamic stimuli with different gradients throughout the vascular network. Adequate adaptation requires endothelial cells to be highly plastic, which is reflected by the remarkable heterogeneity of endothelial cells in tissues and organs. Hemodynamic forces such as fluid shear stress and cyclic strain are strong modulators of the endothelial phenotype and function. Although endothelial plasticity is essential during development and adult physiology, proatherogenic stimuli can induce adverse plasticity which contributes to disease. Endothelial-to-mesenchymal transition (EndMT), the hallmark of endothelial plasticity, was long thought to be restricted to embryonic development but has emerged as a pathologic process in a plethora of diseases. In this perspective we argue how shear stress and cyclic strain can modulate EndMT and discuss how this is reflected in atherosclerosis and pulmonary arterial hypertension. PMID:26904133

  6. Interactions between stainless steel, shear stress, and monocytes.

    PubMed

    Messer, Regina L W; Mickalonis, John; Lewis, Jill B; Omata, Yo; Davis, Cortney M; Brown, Yolanda; Wataha, John C

    2008-10-01

    Angioplasty with stent placement is commonly used to treat coronary atherosclerosis. However, 20-40% of stainless steel stents restenose within 6 months via a prolonged inflammatory response mediated by monocytic infiltration and cytokine secretion. In the current study, we tested a hypothesis that blood flow and monocytes interact to alter stent corrosion. We assessed the effects of THP1 monocytes on the corrosion rate of 316L stainless steel (316LSS) under shear stress (0.5-50 dyn/cm(2)). In addition, THP1 cytokine secretion was determined using cytokine arrays and ELISA analyses. Data were compared using ANOVA and Tukey post hoc analysis (alpha = 0.05). Monocytes significantly lowered 316LSS corrosion rates without limiting current density. However, shear stress alone did not alter the corrosion rate of 316LSS. THP1 cells adhered to the 316LSS surface at all flow rates. Exposure to the 316LSS/corrosion test under high fluid flow rates increased (>twofold) the secretion of 7 of the 42 cytokines tested (angeogenin, GRO, I309, interleukin 8, interleukin 6, interleukin 1beta, and macrophage chemoattractant protein-1). Each of these cytokines play a role in wound healing, macrophage differentiation, and cell proliferation, all hallmarks of in-stent restenosis. Furthermore, only IL8 levels were significantly higher than any of the system controls during the 316LSS/corrosion test conditions. The IL8 levels from the 316LSS/corrosion tests were not significantly different from the +LPS control. Together, these data suggest that monocytic cells maybe activated by exposure to 316LSS stents and could contribute to in-stent restenosis and altered corrosion of the stent.

  7. Understanding the fluid mechanics behind transverse wall shear stress.

    PubMed

    Mohamied, Yumnah; Sherwin, Spencer J; Weinberg, Peter D

    2017-01-04

    The patchy distribution of atherosclerosis within arteries is widely attributed to local variation in haemodynamic wall shear stress (WSS). A recently-introduced metric, the transverse wall shear stress (transWSS), which is the average over the cardiac cycle of WSS components perpendicular to the temporal mean WSS vector, correlates particularly well with the pattern of lesions around aortic branch ostia. Here we use numerical methods to investigate the nature of the arterial flows captured by transWSS and the sensitivity of transWSS to inflow waveform and aortic geometry. TransWSS developed chiefly in the acceleration, peak systolic and deceleration phases of the cardiac cycle; the reverse flow phase was too short, and WSS in diastole was too low, for these periods to have a significant influence. Most of the spatial variation in transWSS arose from variation in the angle by which instantaneous WSS vectors deviated from the mean WSS vector rather than from variation in the magnitude of the vectors. The pattern of transWSS was insensitive to inflow waveform; only unphysiologically high Womersley numbers produced substantial changes. However, transWSS was sensitive to changes in geometry. The curvature of the arch and proximal descending aorta were responsible for the principal features, the non-planar nature of the aorta produced asymmetries in the location and position of streaks of high transWSS, and taper determined the persistence of the streaks down the aorta. These results reflect the importance of the fluctuating strength of Dean vortices in generating transWSS.

  8. MicroRNA-30 mediates anti-inflammatory effects of shear stress and KLF2 via repression of angiopoietin 2.

    PubMed

    Demolli, Shemsi; Doebele, Carmen; Doddaballapur, Anuradha; Lang, Victoria; Fisslthaler, Beate; Chavakis, Emmanouil; Vinciguerra, Manlio; Sciacca, Sergio; Henschler, Reinhard; Hecker, Markus; Savant, Soniya; Augustin, Hellmut G; Kaluza, David; Dimmeler, Stefanie; Boon, Reinier A

    2015-11-01

    MicroRNAs are endogenously expressed small noncoding RNAs that regulate gene expression. Laminar blood flow induces atheroprotective gene expression in endothelial cells (ECs) in part by upregulating the transcription factor KLF2. Here, we identified KLF2- and flow-responsive miRs that affect gene expression in ECs. Bioinformatic assessment of mRNA expression patterns identified the miR-30-5p seed sequence to be highly enriched in mRNAs that are downregulated by KLF2. Indeed, KLF2 overexpression and shear stress stimulation in vitro and in vivo increased the expression of miR-30-5p family members. Furthermore, we identified angiopoietin 2 (Ang2) as a target of miR-30. MiR-30 overexpression reduces Ang2 levels, whereas miR-30 inhibition by LNA-antimiRs induces Ang2 expression. Consistently, miR-30 reduced basal and TNF-α-induced expression of the inflammatory cell–cell adhesion molecules E-selectin, ICAM1 and VCAM1, which was rescued by stimulation with exogenous Ang2. In summary, KLF2 and shear stress increase the expression of the miR-30-5p family which acts in an anti-inflammatory manner in ECs by impairing the expression of Ang2 and inflammatory cell–cell adhesion molecules. The upregulation of miR-30-5p family members may contribute to the atheroprotective effects of shear stress.

  9. Predicting boundary shear stress and sediment transport over bed forms

    USGS Publications Warehouse

    McLean, S.R.; Wolfe, S.R.; Nelson, J.M.

    1999-01-01

    To estimate bed-load sediment transport rates in flows over bed forms such as ripples and dunes, spatially averaged velocity profiles are frequently used to predict mean boundary shear stress. However, such averaging obscures the complex, nonlinear interaction of wake decay, boundary-layer development, and topographically induced acceleration downstream of flow separation and often leads to inaccurate estimates of boundary stress, particularly skin friction, which is critically important in predicting bed-load transport rates. This paper presents an alternative methodology for predicting skin friction over 2D bed forms. The approach is based on combining the equations describing the mechanics of the internal boundary layer with semiempirical structure functions to predict the velocity at the crest of a bedform, where the flow is most similar to a uniform boundary layer. Significantly, the methodology is directed toward making specific predictions only at the bed-form crest, and as a result it avoids the difficulty and questionable validity of spatial averaging. The model provides an accurate estimate of the skin friction at the crest where transport rates are highest. Simple geometric constraints can be used to derive the mean transport rates as long as bed load is dominant.To estimate bed-load sediment transport rates in flows over bed forms such as ripples and dunes, spatially averaged velocity profiles are frequently used to predict mean boundary shear stress. However, such averaging obscures the complex, nonlinear interaction of wake decay, boundary-layer development, and topographically induced acceleration downstream of flow separation and often leads to inaccurate estimates of boundary stress, particularly skin friction, which is critically important in predicting bed-load transport rates. This paper presents an alternative methodology for predicting skin friction over 2D bed forms. The approach is based on combining the equations describing the mechanics of

  10. Differential roles for endothelial ICAM-1, ICAM-2, and VCAM-1 in shear-resistant T cell arrest, polarization, and directed crawling on blood-brain barrier endothelium.

    PubMed

    Steiner, Oliver; Coisne, Caroline; Cecchelli, Roméo; Boscacci, Rémy; Deutsch, Urban; Engelhardt, Britta; Lyck, Ruth

    2010-10-15

    Endothelial ICAM-1 and ICAM-2 were shown to be essential for T cell diapedesis across the blood-brain barrier (BBB) in vitro under static conditions. Crawling of T cells prior to diapedesis was only recently revealed to occur preferentially against the direction of blood flow on the endothelial surface of inflamed brain microvessels in vivo. Using live cell-imaging techniques, we prove that Th1 memory/effector T cells predominantly crawl against the direction of flow on the surface of BBB endothelium in vitro. Analysis of T cell interaction with wild-type, ICAM-1-deficient, ICAM-2-deficient, or ICAM-1 and ICAM-2 double-deficient primary mouse brain microvascular endothelial cells under physiological flow conditions allowed us to dissect the individual contributions of endothelial ICAM-1, ICAM-2, and VCAM-1 to shear-resistant T cell arrest, polarization, and crawling. Although T cell arrest was mediated by endothelial ICAM-1 and VCAM-1, T cell polarization and crawling were mediated by endothelial ICAM-1 and ICAM-2 but not by endothelial VCAM-1. Therefore, our data delineate a sequential involvement of endothelial ICAM-1 and VCAM-1 in mediating shear-resistant T cell arrest, followed by endothelial ICAM-1 and ICAM-2 in mediating T cell crawling to sites permissive for diapedesis across BBB endothelium.

  11. Surface temperatures and glassy state investigations in tribology, part 3. [limiting shear stress rheological model

    NASA Technical Reports Server (NTRS)

    Bair, S.; Winer, W. O.

    1980-01-01

    Research related to the development of the limiting shear stress rheological model is reported. Techniques were developed for subjecting lubricants to isothermal compression in order to obtain relevant determinations of the limiting shear stress and elastic shear modulus. The isothermal compression limiting shear stress was found to predict very well the maximum traction for a given lubricant. Small amounts of side slip and twist incorporated in the model were shown to have great influence on the rising portion of the traction curve at low slide-roll ratio. The shear rheological model was also applied to a Grubin-like elastohydrodynamic inlet analysis for predicting film thicknesses when employing the limiting shear stress model material behavior.

  12. Modeling aeolian sediment transport thresholds on physically rough Martian surfaces: A shear stress partitioning approach

    NASA Astrophysics Data System (ADS)

    Gillies, John A.; Nickling, William G.; King, James; Lancaster, Nicholas

    2010-09-01

    This paper explores the effect that large roughness elements (0.30 m × 0.26 m × 0.36 m) may have on entrainment of sediment by Martian winds using a shear stress partitioning approach based on a model developed by Raupach et al. (Raupach, M.R., Gillette, D.A., Leys, J.F., 1993. The effect of roughness elements on wind erosion threshold. Journal of Geophysical Research 98(D2), 3023-3029). This model predicts the shear stress partitioning ratio defined as the percent reduction in shear stress on the intervening surface between the roughness elements as compared to the surface in the absence of those elements. This ratio is based on knowledge of the geometric properties of the roughness elements, the characteristic drag coefficients of the elements and the surface, and the assumed effect these elements have on the spatial distribution of the mean and maximum shear stresses. On Mars, unlike on Earth, the shear stress partitioning caused by roughness can be non-linear in that the drag coefficients for the surface as well as for the roughness itself show Reynolds number dependencies for the reported range of Martian wind speeds. The shear stress partitioning model of Raupach et al. is used to evaluate how conditions of the Martian atmosphere will affect the threshold shear stress ratio for Martian surfaces over a range of values of roughness density. Using, as an example, a 125 µm diameter particle with an estimated threshold shear stress on Mars of ≈ 0.06 N m - 2 (shear velocity, u* ≈ 2 m s - 1 on a smooth surface), we evaluate the effect of roughness density on the threshold shear stress ratio for this diameter particle. In general, on Mars higher regional shear stresses are required to initiate particle entrainment for surfaces that have the same physical roughness as defined by the roughness density term ( λ) compared with terrestrial surfaces mainly because of the low Martian atmospheric density.

  13. Shear stress partitioning of overland flow on disturbed and undisturbed rangelands

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physically-based hillslope erosion models commonly estimate soil detachment and transport capacity based on overland flow shear stress applied to soil aggregates. However, vegetation and rock cover counteract the shear stress of overland flow where they occur. Accordingly, partitioning of total sh...

  14. Wall Shear Stress, Wall Pressure and Near Wall Velocity Field Relationships in a Whirling Annular Seal

    NASA Technical Reports Server (NTRS)

    Morrison, Gerald L.; Winslow, Robert B.; Thames, H. Davis, III

    1996-01-01

    The mean and phase averaged pressure and wall shear stress distributions were measured on the stator wall of a 50% eccentric annular seal which was whirling in a circular orbit at the same speed as the shaft rotation. The shear stresses were measured using flush mounted hot-film probes. Four different operating conditions were considered consisting of Reynolds numbers of 12,000 and 24,000 and Taylor numbers of 3,300 and 6,600. At each of the operating conditions the axial distribution (from Z/L = -0.2 to 1.2) of the mean pressure, shear stress magnitude, and shear stress direction on the stator wall were measured. Also measured were the phase averaged pressure and shear stress. These data were combined to calculate the force distributions along the seal length. Integration of the force distributions result in the net forces and moments generated by the pressure and shear stresses. The flow field inside the seal operating at a Reynolds number of 24,000 and a Taylor number of 6,600 has been measured using a 3-D laser Doppler anemometer system. Phase averaged wall pressure and wall shear stress are presented along with phase averaged mean velocity and turbulence kinetic energy distributions located 0.16c from the stator wall where c is the seal clearance. The relationships between the velocity, turbulence, wall pressure and wall shear stress are very complex and do not follow simple bulk flow predictions.

  15. Fluid shear stress sensitizes cancer cells to receptor-mediated apoptosis via trimeric death receptors

    NASA Astrophysics Data System (ADS)

    Mitchell, Michael J.; King, Michael R.

    2013-01-01

    Cancer metastasis, the process of cancer cell migration from a primary to distal location, typically leads to a poor patient prognosis. Hematogenous metastasis is initiated by intravasation of circulating tumor cells (CTCs) into the bloodstream, which are then believed to adhere to the luminal surface of the endothelium and extravasate into distal locations. Apoptotic agents such as tumor necrosis factor apoptosis-inducing ligand (TRAIL), whether in soluble ligand form or expressed on the surface of natural killer cells, have shown promise in treating CTCs to reduce the probability of metastasis. The role of hemodynamic shear forces in altering the cancer cell response to apoptotic agents has not been previously investigated. Here, we report that human colon cancer COLO 205 and prostate cancer PC-3 cells exposed to a uniform fluid shear stress in a cone-and-plate viscometer become sensitized to TRAIL-induced apoptosis. Shear-induced sensitization directly correlates with the application of fluid shear stress, and TRAIL-induced apoptosis increases in a fluid shear stress force- and time-dependent manner. In contrast, TRAIL-induced necrosis is not affected by the application fluid shear stress. Interestingly, fluid shear stress does not sensitize cancer cells to apoptosis when treated with doxorubicin, which also induces apoptosis in cancer cells. Caspase inhibition experiments reveal that shear stress-induced sensitization to TRAIL occurs via caspase-dependent apoptosis. These results suggest that physiological fluid shear forces can modulate receptor-mediated apoptosis of cancer cells in the presence of apoptotic agents.

  16. Response of hot element wall shear stress gages in laminar oscillating flows

    NASA Technical Reports Server (NTRS)

    Cook, W. J.; Murphy, J. D.; Giddings, T. A.

    1986-01-01

    An experimental investigation of the time-dependent response of hot element wall shear stress gages in unsteady periodic air flows is reported. The study has focused on wall shear stress in laminar oscillating flows produced on a flat plate by a free stream velocity composed of a mean component and a superposed sinusoidal variation. Two types of hot element gages, platinum film and flush wire, were tested for values of reduced frequency ranging from 0.14 to 2.36. Values of the phase angle of the wall shear stress variation relative to the free stream velocity, as indicated by the hot element gages, are compared with numerical prediction. The comparisons show that the gages indicate a wall shear stress variation that lags the true variation, and that the gages will also not indicate the correct wall shear stress variation in periodic turbulent flows.

  17. Intracellular pH changes in human aortic smooth muscle cells in response to fluid shear stress

    NASA Technical Reports Server (NTRS)

    Stamatas, G. N.; Patrick, C. W. Jr; McIntire, L. V.

    1997-01-01

    The smooth muscle cell (SMC) layers of human arteries may be exposed to blood flow after endothelium denudation, for example, following balloon angioplasty treatment. These SMCs are also constantly subjected to pressure driven transmural fluid flow. Flow-induced shear stress can alter SMC growth and metabolism. Signal transduction mechanisms involved in these flow effects on SMCs are still poorly understood. In this work, the hypothesis that shear stress alters the intracellular pH (pHi) of SMC is examined. When exposed to venous and arterial levels of shear stress, human aortic smooth muscle cells (hASMC) undergo alkalinization. The alkalinization plateau persisted even after 20 min of cell exposure to flow. Addition of amiloride (10 micromoles) or its 5-(N-ethyl-N-isopropyl) analog (EIPA, 10 micromoles), both Na+/H+ exchanger inhibitors, attenuated intracellular alkalinization, suggesting the involvement of the Na+/H+ exchanger in this response. The same concentrations of these inhibitors did not show an effect on pHi of hASMCs in static culture. 4-Acetamido-4'-isothio-cyanatostilbene-2,2'-disulfonic acid (SITS, 1 mM), a Cl-/HCO3- exchange inhibitor, affected the pHi of hASMCs both in static and flow conditions. Our results suggest that flow may perturb the Na+/H+ exchanger leading to an alkalinization of hASMCs, a different response from the flow-induced acidification seen with endothelial cells at the same levels of shear stress. Understanding the flow-induced signal transduction pathways in the vascular cells is of great importance in the tissue engineering of vascular grafts. In the case of SMCs, the involvement of pHi changes in nitric oxide production and proliferation regulation highlights further the significance of such studies.

  18. Optimization of MR phase-contrast-based flow velocimetry and shear stress measurements.

    PubMed

    Kim, Taeho; Seo, Ji-Hyea; Bang, Seong-Sik; Choi, Hyeon-Woo; Chang, Yongmin; Lee, Jongmin

    2010-02-01

    This study was designed to measure the pixel-by-pixel flow velocity and shear stress from phase-contrast MR images. An optimized method was suggested and the use of the method was confirmed. A self-developed, straight steady flow model system was scanned by MRI with a velocity-encoded phase-contrast sequence. In-house developed software was used for the pixel-by-pixel flow velocity and shear stress measurements and the measurements were compared with physically measured mean velocity and shear stress. A comparison between the use of the in-house velocimetry software and a commercial velocimetry system was also performed. Curved steady flow models were scanned by phase-contrast MRI. Subsequently, velocity and shear stress were measured to confirm the shifted peak flow velocity and shear stress toward the outer side of the lumen. Peak velocity and shear stress were calculated for both the inner and outer half of the lumen and were statistically compared. The mean velocity measured with the use of in-house software had a significant correlation with the physical measurements of mean velocity; in addition, the measurement was more precise compared to the commercial system (R(2) = 0.85 vs. 0.75, respectively). The calculated mean shear stress had a significant correlation with the physical measurements of mean shear stress (R(2) = 0.95). The curved flow model showed a significantly shifted peak velocity and shear stress zones toward the outside of the flow (P < 0.0001). The technique to measure pixel-by-pixel velocity and shear stress of steady flow from velocity-encoded phase-contrast MRI was optimized. This technique had a good correlation with physical measurements and was superior to a commercially available system.

  19. Characteristics of the response of the iliac artery to wall shear stress in the anaesthetized pig.

    PubMed

    Kelly, R F; Snow, H M

    2007-07-15

    The functional significance of shear stress-induced vasodilatation in large conduit arteries is unclear since changes in the diameter have little effect on the resistance to blood flow. However, changes in diameter have a relatively large effect on wall shear stress which suggests that the function of flow-mediated dilatation is to reduce wall shear stress. The mean and pulsatile components of shear stress vary widely throughout the arterial system and areas of low mean and high amplitude of wall shear stress are prone to the development of atheroma. In this study, using an in vivo model with the ability to control flow rate and amplitude of flow independently, we investigated the characteristics of the response of the iliac artery to variations in both the mean and amplitude of wall shear stress. The results of this study confirm that increases in mean wall shear stress are an important stimulus for the release of nitric oxide by the endothelium as indicated by changes in arterial diameter and show for the first time, in vivo, that increases in the amplitude of the pulsatile component of shear stress have a small but significant inhibitory effect on this response. A negative feedback mechanism was identified whereby increases in shear stress brought about by increases in blood flow are reduced by the release of nitric oxide from the endothelium causing dilatation of the artery, thus decreasing the stimulus to cell adhesion and, through a direct action of nitric oxide, inhibiting the process of cell adhesion. The results also provide an explanation for the uneven distribution of atheroma throughout the arterial system, which is related to the ratio of pulsatile to mean shear stress and consequent variability in the production of NO.

  20. Critical combinations of shear and direct axial stress for curved rectangular panels

    NASA Technical Reports Server (NTRS)

    Schildcrout, Murry; Stein, Manuel

    1949-01-01

    A solution is presented for the problem of the buckling of curved rectangular panels subjected to combined shear and direct axial stress. Charts giving theoretical critical combinations of shear and direct axial stress are presented for panels having five different length-width ratios. Because the actual critical compressive stress of rectangular panels having substantial curvature is known to be much lower than the theoretical value, a semiempirical method of analysis of curved panels subjected to combined shear and direct axial stress is presented for use in design. (author

  1. Capillary tone: cyclooxygenase, shear stress, luminal glycocalyx, and hydraulic conductivity (Lp)

    PubMed Central

    Williams, Donna A; Flood, Mary H

    2015-01-01

    Control of capillary hydraulic conductivity (Lp) is the physiological mechanism that underpins systemic hydration. Capillaries form the largest surface of endothelial cells in any species with a cardiovascular system and all capillaries are exposed to the flow-induced force, shear stress (τ). Vasoactive molecules such as prostacyclin (cyclooxygenase product, COX) are released from endothelial cells in response to τ. Little is known about how COX activity impacts capillary Lp. The purpose here was to assess Lp in situ following an acute Δτ stimulus and during COX1/COX2 inhibition. Mesenteric true capillaries (TC) of Rana pipiens (pithed) were cannulated for Lp assessment using the modified Landis technique. Rana were randomized into Control and Test groups. Two capillaries per animal were used (perfusate, 10 mg·mL−1 BSA/frog Ringer's; superfusate, frog Ringer's or indomethacin (10−5 mol·L−1) mixed in frog Ringer's solution). Three distinct responses of Lp to indomethacin (TC2) were demonstrated (TC1 and TC2 medians: Test Subgroup 1, 3.0 vs. 1.8; Test Subgroup 2, 18.2 vs. 2.2; Test Subgroup 3, 4.2 vs. 10.2 × 10−7 cm·sec−1·cm H2O−1). Multiple regression analysis revealed a relationship between capillary Lp and systemic red blood cell concentration or hematocrit, plasma protein concentration, and Δτ (Test Subgroup 1, R2 = 0.59, P < 0.0001; Test Subgroup 2, R2 = 0.96, P = 0.002), but only during COX inhibition. Maintaining red blood cell and plasma protein levels within a normal range may control barrier function in a healthy state. Recovering barrier function may be an unrecognized benefit of transfusions during blood loss or edema formation. PMID:25896981

  2. Capillary tone: cyclooxygenase, shear stress, luminal glycocalyx, and hydraulic conductivity (Lp).

    PubMed

    Williams, Donna A; Flood, Mary H

    2015-04-01

    Control of capillary hydraulic conductivity (Lp) is the physiological mechanism that underpins systemic hydration. Capillaries form the largest surface of endothelial cells in any species with a cardiovascular system and all capillaries are exposed to the flow-induced force, shear stress (τ). Vasoactive molecules such as prostacyclin (cyclooxygenase product, COX) are released from endothelial cells in response to τ. Little is known about how COX activity impacts capillary Lp. The purpose here was to assess Lp in situ following an acute Δτ stimulus and during COX1/COX2 inhibition. Mesenteric true capillaries (TC) of Rana pipiens (pithed) were cannulated for Lp assessment using the modified Landis technique. Rana were randomized into Control and Test groups. Two capillaries per animal were used (perfusate, 10 mg·mL(-1) BSA/frog Ringer's; superfusate, frog Ringer's or indomethacin (10(-5) mol·L(-1)) mixed in frog Ringer's solution). Three distinct responses of Lp to indomethacin (TC2) were demonstrated (TC1 and TC2 medians: Test Subgroup 1, 3.0 vs. 1.8; Test Subgroup 2, 18.2 vs. 2.2; Test Subgroup 3, 4.2 vs. 10.2 × 10(-7) cm·sec(-1)·cm H2O(-1)). Multiple regression analysis revealed a relationship between capillary Lp and systemic red blood cell concentration or hematocrit, plasma protein concentration, and Δτ (Test Subgroup 1, R(2) = 0.59, P < 0.0001; Test Subgroup 2, R(2) = 0.96, P = 0.002), but only during COX inhibition. Maintaining red blood cell and plasma protein levels within a normal range may control barrier function in a healthy state. Recovering barrier function may be an unrecognized benefit of transfusions during blood loss or edema formation.

  3. The production of turbulent stress in a shear flow by irrotational fluctuations

    NASA Technical Reports Server (NTRS)

    Gartshore, I. S.; Durbin, P. A.; Hunt, J. C. R.

    1983-01-01

    Attention is given to the way in which external turbulence affects an initially turbulence-free region in which there is a mean velocity gradient. External turbulence induces irrotational fluctuations in the sheared region which interact with the shear to produce rotational velocity fluctuations and mean Reynolds stresses. Since the actual front between the initial external turbulence and the shear flow is a randomly contorted surface, the turbulence near the front is intermittent, and is presently included in the form of a simple statistical model. In wind tunnel tests, turbulent shear stress was found to grow from zero to significant values in the interaction region. Observed stress magnitude and extent agrees with predictions, and it is concluded that turbulent stresses can be produced by irrotational fluctuations in a region of mean shear.

  4. Wall Shear Stress in Aorta with Coarctation and Post-Stenotic Dilatation - Scale Resolved Simulation of Pulsatile Blood Flow

    NASA Astrophysics Data System (ADS)

    Gardhagen, Roland; Karlsson, Matts

    2012-11-01

    Large eddy simulations of pulsating blood flow in an idealized model of a human aorta with a coarctation and a post-stenotic dilatation were conducted before and after treatment of the stenosis using Ansys Fluent. The aim was to study wall shear stress (WSS), which influences the function of endothelial cells, and turbulence, which may play a role in thrombus formation. Phase average values of WSS before the treatment revealed high shear in the stenosis at peak systole, as expected, but also at the end of the dilatation. In the dilatation backflow causes a negative peak. Diastolic WSS is characterized by low amplitude oscillations, which promotes atherogenesis. Also noticeable is the asymmetric pattern between the inner and outer sides of the vessel caused by the arch upstream of the stenosis. Thus, large spatial, temporal, and probably asymmetric WSS gradients in the already diseased region suggest increased risk for further endothelial dysfunction. This reflects a complex, partly turbulent, flow pattern that may disturb the blood flow in the abdominal aorta. After treatment of the stenosis, but not the dilatation, fluctuations of velocity and WSS were still found, thus harmful flow conditions still exist.

  5. In vitro, time-resolved PIV comparison of the effect of stent design on wall shear stress.

    PubMed

    Charonko, John; Karri, Satyaprakash; Schmieg, Jaime; Prabhu, Santosh; Vlachos, Pavlos

    2009-07-01

    The effect of stent design on wall shear stress (WSS) and oscillatory shear index (OSI) was studied in vitro using time-resolved digital particle image velocimetry (DPIV). Four drug-eluting stents [XIENCE V (Abbott Vascular), TAXUS Liberté (Boston Scientific), Endeavor (Medtronic), and Cypher (J&J Cordis)] and a bare-metal stent [VISION (Abbott Vascular)] were implanted into compliant vessel models, and the flow was measured in physiologically accurate coronary conditions featuring reversal and realistic offsets between pressure and flowrate. DPIV measurements were made at three locations under two different flow rates (resting: Re = 160, f = 70 bpm and exercise: Re = 300, f = 120 bpm). It was observed that design substantially affected the WSS experienced at the vessel walls. Averaged values between struts ranged from 2.05 dynes/cm(2) (Cypher) to 8.52 dynes/cm(2) (XIENCE V) in resting conditions, and from 3.72 dynes/cm(2) (Cypher) to 14.66 dynes/cm(2) (VISION) for the exercise state. Within the stent, the WSS dropped and the OSI increased immediately distal to each strut. In addition, an inverse correlation between average WSS and OSI existed. Comparisons with recently published results from animal studies show strong correlation between the measured WSS and observed endothelial cell coverage. These results suggest the importance of stent design on the WSS experienced by endothelial cells in coronary arteries.

  6. Contact Pressure and Shear Stress Analysis on Conforming Contact Problem

    NASA Astrophysics Data System (ADS)

    Nagatani, Haruo; Imou, Akitoshi

    Two methods to solve a conforming contact problem are proposed. First method is general and can be applicable to the contact case between elastic arbitrary shape bodies. For verification FEA is performed on the convex-concave sphere contact, and the result of this method is well corresponding to the FEA result. However, the accuracy deteriorates when the mesh aspect ratio is extremely large. This phenomenon is caused by the usage of numerical integration for the calculation of influence coefficient. The second method is devised to avoid this problem, while this improved method is applicable only to the case when the contact area can be considered to be on a cylinder surface. By using this method, the contact pressure can be obtained without the deterioration even in the case of edge load occurring between ball bearing race shoulder and ball. The results of the contact pressure and the shear stress that is necessary for bearing life estimation are compared with the FEA result, which showed well correspondence.

  7. Surface chemistry modulates osteoblasts sensitivity to low fluid shear stress.

    PubMed

    Xing, Juan; Li, Yan; Lin, Manping; Wang, Jinfeng; Wu, Jinchuan; Ma, Yufei; Wang, Yuanliang; Yang, Li; Luo, Yanfeng

    2014-11-01

    Low fluid shear stress (FSS) is the mechanical environment encountered by osteoblasts in implanted bones or native bones of bed rest patients. High sensitivity of osteoblasts to low FSS is beneficial to osteogenesis. We hypothesize that this sensitivity might be regulated by chemical microenvironment provided by scaffolds. To confirm this hypothesis, self-assembled monolayers (SAMs) were used to provide various surface chemistries including OH, CH3 , and NH2 while parallel-plate fluid flow system produced low FSS (5 dynes/cm(2) ). Alterations in S-phase cell fraction, alkaline phosphatase activity, fibronectin (Fn), and collagen type I (COL I) secretion compared to those without FSS exposure were detected to characterize the sensitivity. Osteoblasts on OH and CH3 SAMs demonstrated obvious sensitivity while on NH2 SAMs negligible sensitivity was observed. Examination of the cell aspect ratio, orientation, and focal adhesions before and after FSS exposure indicates that the full spreading and robust focal adhesions on NH2 SAMs should be responsible for the negligible sensitivity through increasing the cell tolerance to low FSS. Despite the higher sensitivity, the Fn and COL I depositions on both OH and CH3 SAMs after FSS exposure were still less than on NH2 SAMs without FSS exposure. These results suggest that elaborate design of surface chemical compositions is essential for orchestration of surface chemistry with low FSS to realize both high sensitivity and high matrix secretion, facilitating the formation of functional bone tissues in implanted bone.

  8. Characterizations and Correlations of Wall Shear Stress in Aneurysmal Flow

    PubMed Central

    Arzani, Amirhossein; Shadden, Shawn C.

    2016-01-01

    Wall shear stress (WSS) is one of the most studied hemodynamic parameters, used in correlating blood flow to various diseases. The pulsatile nature of blood flow, along with the complex geometries of diseased arteries, produces complicated temporal and spatial WSS patterns. Moreover, WSS is a vector, which further complicates its quantification and interpretation. The goal of this study is to investigate WSS magnitude, angle, and vector changes in space and time in complex blood flow. Abdominal aortic aneurysm (AAA) was chosen as a setting to explore WSS quantification. Patient-specific computational fluid dynamics (CFD) simulations were performed in six AAAs. New WSS parameters are introduced, and the pointwise correlation among these, and more traditional WSS parameters, was explored. WSS magnitude had positive correlation with spatial/temporal gradients of WSS magnitude. This motivated the definition of relative WSS gradients. WSS vectorial gradients were highly correlated with magnitude gradients. A mix WSS spatial gradient and a mix WSS temporal gradient are proposed to equally account for variations in the WSS angle and magnitude in single measures. The important role that WSS plays in regulating near wall transport, and the high correlation among some of the WSS parameters motivates further attention in revisiting the traditional approaches used in WSS characterizations. PMID:26592536

  9. Design of cellular porous biomaterials for wall shear stress criterion.

    PubMed

    Chen, Yuhang; Zhou, Shiwei; Cadman, Joseph; Li, Qing

    2010-11-01

    The microfluidic environment provided by implanted prostheses has a decisive influence on the viability, proliferation and differentiation of cells. In bone tissue engineering, for instance, experiments have confirmed that a certain level of wall shear stress (WSS) is more advantageous to osteoblastic differentiation. This paper proposes a level-set-based topology optimization method to regulate fluidic WSS distribution for design of cellular biomaterials. The topological boundary of fluid phase is represented by a level-set model embedded in a higher-dimensional scalar function. WSS is determined by the computational fluid dynamics analysis in the scale of cellular base cells. To achieve a uniform WSS distribution at the solid-fluid interface, the difference between local and target WSS is taken as the design criterion, which determines the speed of the boundary evolution in the level-set model. The examples demonstrate the effectiveness of the presented method and exhibit a considerable potential in the design optimization and fabrication of new prosthetic cellular materials for bioengineering applications.

  10. Flow instability and wall shear stress variation in intracranial aneurysms

    PubMed Central

    Baek, H.; Jayaraman, M. V.; Richardson, P. D.; Karniadakis, G. E.

    2010-01-01

    We investigate the flow dynamics and oscillatory behaviour of wall shear stress (WSS) vectors in intracranial aneurysms using high resolution numerical simulations. We analyse three representative patient-specific internal carotid arteries laden with aneurysms of different characteristics: (i) a wide-necked saccular aneurysm, (ii) a narrower-necked saccular aneurysm, and (iii) a case with two adjacent saccular aneurysms. Our simulations show that the pulsatile flow in aneurysms can be subject to a hydrodynamic instability during the decelerating systolic phase resulting in a high-frequency oscillation in the range of 20–50 Hz, even when the blood flow rate in the parent vessel is as low as 150 and 250 ml min−1 for cases (iii) and (i), respectively. The flow returns to its original laminar pulsatile state near the end of diastole. When the aneurysmal flow becomes unstable, both the magnitude and the directions of WSS vectors fluctuate at the aforementioned high frequencies. In particular, the WSS vectors around the flow impingement region exhibit significant spatio-temporal changes in direction as well as in magnitude. PMID:20022896

  11. Vascular wall shear stress in zebrafish model of early atherosclerosis

    NASA Astrophysics Data System (ADS)

    Choi, Woorak; Seo, Eunseok; Yeom, Eunseop; Lee, Sang Joon

    2016-11-01

    Although atherosclerosis is a multifactorial disease, the role of hemodynamic force has strong influence on the outbreak of the disease. Low and oscillating wall shear stress (WSS) is associated with the incidence of atherosclerosis. Many researchers have investigated relationships between WSS and the occurrence of atherosclerosis using in vitro and in vivo models. However, these models possess technological limitations in mimicking real biophysiological conditions and monitoring the temporal progression of atherosclerosis. In this study, a hypercholesterolaemic zebrafish model was established as a novel model to resolve these technical limitations. WSS in blood vessels of 15 days post-fertilisation zebrafish was measured using a micro PIV technique, and the spatial distribution of lipids inside blood vessels was quantitatively visualized using a confocal microscopy. As a result, lipids are mainly deposited in the regions of low WSS. The oscillating WSS is not induced by blood flows in the zebrafish disease model. The present hypercholesterolaemic zebrafish model would be useful for understanding the effect of WSS on the early stage of atherosclerosis. This work was supported by the National Research Foundation of Korea (NRF) under a Grant funded by the Korean government (MSIP) (No. 2008-0061991).

  12. Shear stress variation induced by red blood cell motion in microvessel.

    PubMed

    Xiong, Wenjuan; Zhang, Junfeng

    2010-08-01

    We simulated red blood cells flowing in microvessel to examine the induced wall shear stress variation. A typical peak-valley-peak structure is observed, and it is analyzed in terms of its magnitude, spatial influencing range, and temporal elapsed duration. Effects of red cell deformability, microvessel size, and flow velocity have been investigated. The corresponding variation characters have also been related to cell deformation and flow field. Simulation results show that the variation magnitude is mainly determined by the gap size between cell and vessel wall, while the spatial range of the shear stress variation depends on the cell length as well as the microvessel size. For a certain point on the vessel wall, the shear stress variation lasts a short time at a higher flow velocity, and vice versa. As the cell concentration in the microvessel increases, the shear stress variation structure changes accordingly with the two peaks from two close cells merging together, and eventually only one peak is observed at a hematocrit of 30.72%. However, the effect of hematocrit on the variation magnitude of shear stress is less obvious, and the dynamic nature of shear stress is still significant. This represents the first attempt to study the dynamic shear stress variation on microvessel as red blood cells flow by, and the information obtained in this study could be valuable to relevant research, for example, the mechanotransduction in the endothelia glycocalyx layer.

  13. Numerical and experimental demonstration of shear stress measurement at thick steel plates using acoustoelasticity

    NASA Astrophysics Data System (ADS)

    Abbasi, Zeynab; Ozevin, Didem

    2015-04-01

    The purpose of this article is to numerically quantify the stress state of complex loaded thick steel plates using the fundamental theory of acoustoelasticity, which is the relationship with stress and ultrasonic velocity in the nonlinear regime. The normal and shear stresses of a thick plate can be measured using a phased array placement of ultrasonic sensors and Rayleigh ultrasonic waves. Three measurement angles (i.e., 0 45 and 90 degrees) are selected since three measurements are needed to solve the stress tensor in an isotropic plate. The ultrasonic data is influenced significantly by the frequency of the Rayleigh waves as well as the thickness of the plate being examined; consequently the overall experimental process is influenced by the measurement parameters. In this study, a numerical demonstration is implemented to extract the nonlinearity coefficients using a 3D structural geometry and Murnaghan material model capable of examining the effects of various plate thicknesses and ultrasonic frequencies on the shear stress measurement. The purpose is that as the thickness becomes smaller, the shear stress becomes negligible at the angled measurement. For thicker cross section, shear stress becomes influential if the depth of penetration of Rayleigh wave is greater than the half of the thickness. The correlation between the depth of penetration and shear stress is then obtained. The numerical results are compared with 1 MHz ultrasonic frequency and a 3/8 inch thick steel plate loaded uniaxially while the measurement direction is angled to have the presence of shear stress in the measurement direction.

  14. Multiplexed Fluid Flow Device to Study Cellular Response to Tunable Shear Stress Gradients.

    PubMed

    Ostrowski, Maggie A; Huang, Eva Y; Surya, Vinay N; Poplawski, Charlotte; Barakat, Joseph M; Lin, Gigi L; Fuller, Gerald G; Dunn, Alexander R

    2016-07-01

    Endothelial cells (ECs) line the interior of blood and lymphatic vessels and experience spatially varying wall shear stress (WSS) as an intrinsic part of their physiological function. How ECs, and mammalian cells generally, sense spatially varying WSS remains poorly understood, due in part to a lack of convenient tools for exposing cells to spatially varying flow patterns. We built a multiplexed device, termed a 6-well impinging flow chamber, that imparts controlled WSS gradients to a six-well tissue culture plate. Using this device, we investigated the migratory response of lymphatic microvascular ECs, umbilical vein ECs, primary fibroblasts, and epithelial cells to WSS gradients on hours to days timescales. We observed that lymphatic microvascular ECs migrate upstream, against the direction of flow, a response that was unique among all the cells types investigated here. Time-lapse, live cell imaging revealed that the microtubule organizing center relocated to the upstream side of the nucleus in response to the applied WSS gradient. To further demonstrate the utility of our device, we screened for the involvement of canonical signaling pathways in mediating this upstream migratory response. These data highlight the importance of WSS magnitude and WSS spatial gradients in dictating the cellular response to fluid flow.

  15. Recapitulating physiological and pathological shear stress and oxygen to model vasculature in health and disease

    NASA Astrophysics Data System (ADS)

    Abaci, Hasan Erbil; Shen, Yu-I.; Tan, Scott; Gerecht, Sharon

    2014-05-01

    Studying human vascular disease in conventional cell cultures and in animal models does not effectively mimic the complex vascular microenvironment and may not accurately predict vascular responses in humans. We utilized a microfluidic device to recapitulate both shear stress and O2 levels in health and disease, establishing a microfluidic vascular model (μVM). Maintaining human endothelial cells (ECs) in healthy-mimicking conditions resulted in conversion to a physiological phenotype namely cell elongation, reduced proliferation, lowered angiogenic gene expression and formation of actin cortical rim and continuous barrier. We next examined the responses of the healthy μVM to a vasotoxic cancer drug, 5-Fluorouracil (5-FU), in comparison with an in vivo mouse model. We found that 5-FU does not induce apoptosis rather vascular hyperpermeability, which can be alleviated by Resveratrol treatment. This effect was confirmed by in vivo findings identifying a vasoprotecting strategy by the adjunct therapy of 5-FU with Resveratrol. The μVM of ischemic disease demonstrated the transition of ECs from a quiescent to an activated state, with higher proliferation rate, upregulation of angiogenic genes, and impaired barrier integrity. The μVM offers opportunities to study and predict human ECs with physiologically relevant phenotypes in healthy, pathological and drug-treated environments.

  16. High wall shear stress and high-risk plaque: an emerging concept.

    PubMed

    Eshtehardi, Parham; Brown, Adam J; Bhargava, Ankit; Costopoulos, Charis; Hung, Olivia Y; Corban, Michel T; Hosseini, Hossein; Gogas, Bill D; Giddens, Don P; Samady, Habib

    2017-01-10

    In recent years, there has been a significant effort to identify high-risk plaques in vivo prior to acute events. While number of imaging modalities have been developed to identify morphologic characteristics of high-risk plaques, prospective natural-history observational studies suggest that vulnerability is not solely dependent on plaque morphology and likely involves additional contributing mechanisms. High wall shear stress (WSS) has recently been proposed as one possible causative factor, promoting the development of high-risk plaques. High WSS has been shown to induce specific changes in endothelial cell behavior, exacerbating inflammation and stimulating progression of the atherosclerotic lipid core. In line with experimental and autopsy studies, several human studies have shown associations between high WSS and known morphological features of high-risk plaques. However, despite increasing evidence, there is still no longitudinal data linking high WSS to clinical events. As the interplay between atherosclerotic plaque, artery, and WSS is highly dynamic, large natural history studies of atherosclerosis that include WSS measurements are now warranted. This review will summarize the available clinical evidence on high WSS as a possible etiological mechanism underlying high-risk plaque development.

  17. Quantification of disturbed wall shear stress patterns in complex cardiovascular flows

    NASA Astrophysics Data System (ADS)

    Arzani, Amirhossein; Shadden, Shawn C.

    2014-11-01

    Wall shear stress (WSS) affects the cardiovascular system in numerous ways, and is thought to play an important role in the pathology of many cardiovascular diseases. The (endothelial) cells lining the inner wall of blood vessels, and perhaps the cells inside the vessel wall, can actively sense WSS and respond both chemically and mechanically. The complexity of WSS in cardiovascular flows extends both spatially and temporally. Furthermore, WSS has magnitude and direction. These facets make simple quantification of WSS in cardiovascular applications difficult. In this study we propose a framework to quantify measures such as WSS angle gradient, WSS magnitude gradient, WSS angle time derivative and WSS magnitude time derivative. We will explain the relation of these parameters to the tensorial WSS gradient and WSS vector time derivative, and propose a new methodology to unify these concepts into a single measure. The correlation between these metrics and more common WSS metrics used in the literature will be demonstrated. For demonstration, these methods will be used for the quantification of complex blood flow inside abdominal aortic aneurysms.

  18. NOX4-dependent Hydrogen peroxide promotes shear stress-induced SHP2 sulfenylation and eNOS activation.

    PubMed

    Sánchez-Gómez, Francisco J; Calvo, Enrique; Bretón-Romero, Rosa; Fierro-Fernández, Marta; Anilkumar, Narayana; Shah, Ajay M; Schröder, Katrin; Brandes, Ralf P; Vázquez, Jesús; Lamas, Santiago

    2015-12-01

    Laminar shear stress (LSS) triggers signals that ultimately result in atheroprotection and vasodilatation. Early responses are related to the activation of specific signaling cascades. We investigated the participation of redox-mediated modifications and in particular the role of hydrogen peroxide (H2O2) in the sulfenylation of redox-sensitive phosphatases. Exposure of vascular endothelial cells to short periods of LSS (12 dyn/cm(2)) resulted in the generation of superoxide radical anion as detected by the formation of 2-hydroxyethidium by HPLC and its subsequent conversion to H2O2, which was corroborated by the increase in the fluorescence of the specific peroxide sensor HyPer. By using biotinylated dimedone we detected increased total protein sulfenylation in the bovine proteome, which was dependent on NADPH oxidase 4 (NOX4)-mediated generation of peroxide. Mass spectrometry analysis allowed us to identify the phosphatase SHP2 as a protein susceptible to sulfenylation under LSS. Given the dependence of FAK activity on SHP2 function, we explored the role of FAK under LSS conditions. FAK activation and subsequent endothelial NO synthase (eNOS) phosphorylation were promoted by LSS and both processes were dependent on NOX4, as demonstrated in lung endothelial cells isolated from NOX4-null mice. These results support the idea that LSS elicits redox-sensitive signal transduction responses involving NOX4-dependent generation of hydrogen peroxide, SHP2 sulfenylation, and ulterior FAK-mediated eNOS activation.

  19. Analysis of the complex stress state during early loading in cylindrical compression-shear specimens

    NASA Astrophysics Data System (ADS)

    Pfeiffer, S.; Frint, P.; F-X Wagner, M.

    2017-03-01

    In most engineering applications, materials are subjected to complex load cases rather than the simple uniaxial ones typically used for material characterization. To experimentally study the material behavior under a combination of compression and shear, an inclined compression specimen can be used. This specimen has been applied in various earlier experimental studies, typically to investigate shear localization under quasi-static or impact loading. In this contribution, we analyze the stress state in a compression-shear specimen in detail using an elastic-ideal plastic finite element simulation. The effects of specimen aspect ratio (height/diameter), inclination angle, and friction conditions between specimen and tool plates are investigated using the material parameters of different conventional steels as input. Shear stress distributions in characteristic shear directions on specific planes in the specimen that control the subsequent plastic deformation behavior are evaluated. Our results show that, even in the absence of friction, shear stresses are distributed heterogeneously in the inclined specimen, which differs from the stress distribution in a conventional compression specimen. Moreover, the highest shear and equivalent stresses always occur at the edges of the short diagonal plane of the specimen, independent of the investigated parameters. This study contributes to a more detailed understanding of the elasto-plastic mechanics in compression-shear specimens, and it specifically provides information for the analysis of the onset of early plastic deformation.

  20. Impact of wall shear stress on initial bacterial adhesion in rotating annular reactor.

    PubMed

    Saur, Thibaut; Morin, Emilie; Habouzit, Frédéric; Bernet, Nicolas; Escudié, Renaud

    2017-01-01

    The objective of this study was to investigate the bacterial adhesion under different wall shear stresses in turbulent flow and using a diverse bacterial consortium. A better understanding of the mechanisms governing microbial adhesion can be useful in diverse domains such as industrial processes, medical fields or environmental biotechnologies. The impact of wall shear stress-four values ranging from 0.09 to 7.3 Pa on polypropylene (PP) and polyvinyl chloride (PVC)-was carried out in rotating annular reactors to evaluate the adhesion in terms of morphological and microbiological structures. A diverse inoculum consisting of activated sludge was used. Epifluorescence microscopy was used to quantitatively and qualitatively characterize the adhesion. Attached bacterial communities were assessed by molecular fingerprinting profiles (CE-SSCP). It has been demonstrated that wall shear stress had a strong impact on both quantitative and qualitative aspects of the bacterial adhesion. ANOVA tests also demonstrated the significant impact of wall shear stress on all three tested morphological parameters (surface coverage, number of objects and size of objects) (p-values < 2.10-16). High wall shear stresses increased the quantity of attached bacteria but also altered their spatial distribution on the substratum surface. As the shear increased, aggregates or clusters appeared and their size grew when increasing the shears. Concerning the microbiological composition, the adhered bacterial communities changed gradually with the applied shear.

  1. Fiber bundle models for stress release and energy bursts during granular shearing

    NASA Astrophysics Data System (ADS)

    Michlmayr, Gernot; Or, Dani; Cohen, Denis

    2012-12-01

    Fiber bundle models (FBMs) offer a versatile framework for representing transitions from progressive to abrupt failure in disordered material. We report a FBM-based description of mechanical interactions and associated energy bursts during shear deformation of granular materials. For strain-controlled shearing, where elements fail in a sequential order, we present analytical expressions for strain energy release and failure statistics. Results suggest that frequency-magnitude characteristics of fiber failure vary considerably throughout progressive shearing. Predicted failure distributions were in good agreement with experimentally observed shear stress fluctuations and associated bursts of acoustic emissions. Experiments also confirm a delayed release of acoustic emission energy relative to shear stress buildup, as anticipated by the model. Combined with data-rich acoustic emission measurements, the modified FBM offers highly resolved contact-scale insights into granular media dynamics of shearing processes.

  2. Red blood cell damage by shear stress for different blood types

    NASA Astrophysics Data System (ADS)

    Arwatz, Gilad; Bedkowski, Katherine; Smits, Alexander

    2011-11-01

    In surgical practice, blood damage caused by medical devices is often a limiting factor in the duration of an acute procedure or in chronic exposures such as hemodialysis. In order to establish guidelines for designing medical devices, a study was conducted to determine the relationship between shear stress and damage to red blood cells using a concentric Couette device. By measuring the hemolysis level for various shear stresses and exposure times, a non-dimensional relationship between shear stress and blood damage for different blood types was established. Funding provided by Princeton University's Project X.

  3. Local Oxidative and Nitrosative Stress Increases in the Microcirculation during Leukocytes-Endothelial Cell Interactions

    PubMed Central

    Kar, Saptarshi; Kavdia, Mahendra

    2012-01-01

    Leukocyte-endothelial cell interactions and leukocyte activation are important factors for vascular diseases including nephropathy, retinopathy and angiopathy. In addition, endothelial cell dysfunction is reported in vascular disease condition. Endothelial dysfunction is characterized by increased superoxide (O2•−) production from endothelium and reduction in NO bioavailability. Experimental studies have suggested a possible role for leukocyte-endothelial cell interaction in the vessel NO and peroxynitrite levels and their role in vascular disorders in the arterial side of microcirculation. However, anti-adhesion therapies for preventing leukocyte-endothelial cell interaction related vascular disorders showed limited success. The endothelial dysfunction related changes in vessel NO and peroxynitrite levels, leukocyte-endothelial cell interaction and leukocyte activation are not completely understood in vascular disorders. The objective of this study was to investigate the role of endothelial dysfunction extent, leukocyte-endothelial interaction, leukocyte activation and superoxide dismutase therapy on the transport and interactions of NO, O2•− and peroxynitrite in the microcirculation. We developed a biotransport model of NO, O2•− and peroxynitrite in the arteriolar microcirculation and incorporated leukocytes-endothelial cell interactions. The concentration profiles of NO, O2•− and peroxynitrite within blood vessel and leukocytes are presented at multiple levels of endothelial oxidative stress with leukocyte activation and increased superoxide dismutase accounted for in certain cases. The results showed that the maximum concentrations of NO decreased ∼0.6 fold, O2•− increased ∼27 fold and peroxynitrite increased ∼30 fold in the endothelial and smooth muscle region in severe oxidative stress condition as compared to that of normal physiologic conditions. The results show that the onset of endothelial oxidative stress can cause an increase

  4. An Experimental Investigation of the Risk of Triggering Geological Disasters by Injection under Shear Stress.

    PubMed

    Liu, Yixin; Xu, Jiang; Peng, Shoujian

    2016-12-08

    Fluid injection has been applied in many fields, such as hazardous waste deep well injection, forced circulation in geothermal fields, hydraulic fracturing, and CO2 geological storage. However, current research mainly focuses on geological data statistics and the dominating effects of pore pressure. There are only a few laboratory-conditioned studies on the role of drilling boreholes and the effect of injection pressure on the borehole wall. Through experimental phenomenology, this study examines the risk of triggering geological disasters by fluid injection under shear stress. We developed a new direct shear test apparatus, coupled Hydro-Mechanical (HM), to investigate mechanical property variations when an intact rock experienced step drilling borehole, fluid injection, and fluid pressure acting on the borehole and fracture wall. We tested the peak shear stress of sandstone under different experimental conditions, which showed that drilling borehole, water injection, and increased pore pressure led to the decrease in peak shear stress. Furthermore, as pore pressure increased, peak shear stress dispersion increased due to crack propagation irregularity. Because the peak shear stress changed during the fluid injection steps, we suggest that the risk of triggering geological disaster with injection under shear stress, pore, borehole, and fluid pressure should be considered.

  5. An Experimental Investigation of the Risk of Triggering Geological Disasters by Injection under Shear Stress

    NASA Astrophysics Data System (ADS)

    Liu, Yixin; Xu, Jiang; Peng, Shoujian

    2016-12-01

    Fluid injection has been applied in many fields, such as hazardous waste deep well injection, forced circulation in geothermal fields, hydraulic fracturing, and CO2 geological storage. However, current research mainly focuses on geological data statistics and the dominating effects of pore pressure. There are only a few laboratory-conditioned studies on the role of drilling boreholes and the effect of injection pressure on the borehole wall. Through experimental phenomenology, this study examines the risk of triggering geological disasters by fluid injection under shear stress. We developed a new direct shear test apparatus, coupled Hydro-Mechanical (HM), to investigate mechanical property variations when an intact rock experienced step drilling borehole, fluid injection, and fluid pressure acting on the borehole and fracture wall. We tested the peak shear stress of sandstone under different experimental conditions, which showed that drilling borehole, water injection, and increased pore pressure led to the decrease in peak shear stress. Furthermore, as pore pressure increased, peak shear stress dispersion increased due to crack propagation irregularity. Because the peak shear stress changed during the fluid injection steps, we suggest that the risk of triggering geological disaster with injection under shear stress, pore, borehole, and fluid pressure should be considered.

  6. An Experimental Investigation of the Risk of Triggering Geological Disasters by Injection under Shear Stress

    PubMed Central

    Liu, Yixin; Xu, Jiang; Peng, Shoujian

    2016-01-01

    Fluid injection has been applied in many fields, such as hazardous waste deep well injection, forced circulation in geothermal fields, hydraulic fracturing, and CO2 geological storage. However, current research mainly focuses on geological data statistics and the dominating effects of pore pressure. There are only a few laboratory-conditioned studies on the role of drilling boreholes and the effect of injection pressure on the borehole wall. Through experimental phenomenology, this study examines the risk of triggering geological disasters by fluid injection under shear stress. We developed a new direct shear test apparatus, coupled Hydro-Mechanical (HM), to investigate mechanical property variations when an intact rock experienced step drilling borehole, fluid injection, and fluid pressure acting on the borehole and fracture wall. We tested the peak shear stress of sandstone under different experimental conditions, which showed that drilling borehole, water injection, and increased pore pressure led to the decrease in peak shear stress. Furthermore, as pore pressure increased, peak shear stress dispersion increased due to crack propagation irregularity. Because the peak shear stress changed during the fluid injection steps, we suggest that the risk of triggering geological disaster with injection under shear stress, pore, borehole, and fluid pressure should be considered. PMID:27929142

  7. Interlaminar shear stress effects on the postbuckling response of graphite-epoxy panels

    NASA Technical Reports Server (NTRS)

    Engelstad, S. P.; Reddy, J. N.; Knight, N. F., Jr.

    1990-01-01

    The objectives of the study are to assess the influence of shear flexibility on overall postbuckling response, and to examine transverse shear stress distributions in relation to panel failure. Nonlinear postbuckling results are obtained for finite element models based on classical laminated plate theory and first-order shear deformation theory. Good correlation between test and analysis is obtained. The results presented in this paper analytically substantiate the experimentally observed failure mode.

  8. Method for measuring surface shear stress magnitude and direction using liquid crystal coatings

    NASA Technical Reports Server (NTRS)

    Reda, Daniel C. (Inventor)

    1995-01-01

    A method is provided for determining surface shear magnitude and direction at every point on a surface. The surface is covered with a shear stress sensitive liquid crystal coating and illuminated by white light from a normal direction. A video camera is positioned at an oblique angle above the surface to observe the color of the liquid crystal at that angle. The shear magnitude and direction are derived from the color information. A method of calibrating the device is also provided.

  9. Experimental measurement of dynamic fluid shear stress on the ventricular surface of the aortic valve leaflet

    PubMed Central

    Yap, Choon Hwai; Saikrishnan, Neelakantan

    2015-01-01

    Aortic valve (AV) calcification is a highly prevalent disease with serious impact on mortality and morbidity. The exact causes and mechanisms of AV calcification are unclear, although previous studies suggest that mechanical forces play a role. It has been clinically demonstrated that calcification preferentially occurs on the aortic surface of the AV. This is hypothesized to be due to differences in the mechanical environments on the two sides of the valve. It is thus necessary to characterize fluid shear forces acting on both sides of the leaflet to test this hypothesis. The current study is one of two studies characterizing dynamic shear stress on both sides of the AV leaflets. In the current study, shear stresses on the ventricular surface of the AV leaflets were measured experimentally on two prosthetic AV models with transparent leaflets in an in vitro pulsatile flow loop using two-component Laser Doppler Velocimetry (LDV). Experimental measurements were utilized to validate a theoretical model of AV ventricular surface shear stress based on the Womersley profile in a straight tube, with corrections for the opening angle of the valve leaflets. This theoretical model was applied to in vivo data based on MRI-derived volumetric flow rates and valve dimension obtained from the literature. Experimental results showed that ventricular surface shear stress was dominated by the streamwise component. The systolic shear stress waveform resembled a half-sinusoid during systole and peaks at 64–71 dyn/cm2, and reversed in direction at the end of systole for 15–25 ms, and reached a significant negative magnitude of 40–51 dyn/cm2. Shear stresses from the theoretical model applied to in vivo data showed that shear stresses peaked at 77–92 dyn/cm2 and reversed in direction for substantial period of time (108–110 ms) during late systole with peak negative shear stress of 35–38 dyn/cm2. PMID:21465260

  10. Effect of Wall Shear Stress on Corrosion Inhibitor Film Performance

    NASA Astrophysics Data System (ADS)

    Canto Maya, Christian M.

    In oil and gas production, internal corrosion of pipelines causes the highest incidence of recurring failures. Ensuring the integrity of ageing pipeline infrastructure is an increasingly important requirement. One of the most widely applied methods to reduce internal corrosion rates is the continuous injection of chemicals in very small quantities, called corrosion inhibitors. These chemical substances form thin films at the pipeline internal surface that reduce the magnitude of the cathodic and/or anodic reactions. However, the efficacy of such corrosion inhibitor films can be reduced by different factors such as multiphase flow, due to enhanced shear stress and mass transfer effects, loss of inhibitor due to adsorption on other interfaces such as solid particles, bubbles and droplets entrained by the bulk phase, and due to chemical interaction with other incompatible substances present in the stream. The first part of the present project investigated the electrochemical behavior of two organic corrosion inhibitors (a TOFA/DETA imidazolinium, and an alkylbenzyl dimethyl ammonium chloride), with and without an inorganic salt (sodium thiosulfate), and the resulting enhancement. The second part of the work explored the performance of corrosion inhibitor under multiphase (gas/liquid, solid/liquid) flow. The effect of gas/liquid multiphase flow was investigated using small and large scale apparatus. The small scale tests were conducted using a glass cell and a submersed jet impingement attachment with three different hydrodynamic patterns (water jet, CO 2 bubbles impact, and water vapor cavitation). The large scale experiments were conducted applying different flow loops (hilly terrain and standing slug systems). Measurements of weight loss, linear polarization resistance (LPR), and adsorption mass (using an electrochemical quartz crystal microbalance, EQCM) were used to quantify the effect of wall shear stress on the performance and integrity of corrosion inhibitor

  11. Visualization and Measurement of Surface Shear Stress Vector Distributions Using Liquid Crystal Coatings

    NASA Technical Reports Server (NTRS)

    Reda, Daniel C.; Wilder, Michael C.

    1998-01-01

    When a shear-sensitive liquid crystal coating is illuminated from the normal direction by white light and observed from an oblique above-plane view angle, its color-change response to shear depends on both shear stress vector magnitude and the direction of the applied shear vector relative to the observer's in-plane line of sight. At any point, the maximum color change is always seen or measured when the local shear vector is aligned with, and directed away from, the observer; the magnitude of the color change at this vector/observer aligned orientation scales directly with shear stress magnitude. Conversely, any point exposed to a shear vector with a component directed toward the observer exhibits a noncolor-change response, always characterized by a rusty red or brown color, independent of both shear magnitude and direction. Based on this knowledge, full-surface shear stress vector visualization and measurement methodologies were formulated and successfully demonstrated. The present paper reviews the observations and measurements that led to the development of these methodologies and applications of both are discussed.

  12. Wall shear stress at the initiation site of cerebral aneurysms.

    PubMed

    Geers, A J; Morales, H G; Larrabide, I; Butakoff, C; Bijlenga, P; Frangi, A F

    2017-02-01

    Hemodynamics are believed to play an important role in the initiation of cerebral aneurysms. In particular, studies have focused on wall shear stress (WSS), which is a key regulator of vascular biology and pathology. In line with the observation that aneurysms predominantly occur at regions of high WSS, such as bifurcation apices or outer walls of vascular bends, correlations have been found between the aneurysm initiation site and high WSS. The aim of our study was to analyze the WSS field at an aneurysm initiation site that was neither a bifurcation apex nor the outer wall of a vascular bend. Ten cases with aneurysms on the A1 segment of the anterior cerebral artery were analyzed and compared with ten controls. Aneurysms were virtually removed from the vascular models of the cases to mimic the pre-aneurysm geometry. Computational fluid dynamics (CFD) simulations were created to assess the magnitude, gradient, multidirectionality, and pulsatility of the WSS. To aid the inter-subject comparison of hemodynamic variables, we mapped the branch surfaces onto a two-dimensional parametric space. This approach made it possible to view the whole branch at once for qualitative evaluation. It also allowed us to empirically define a patch for quantitative analysis, which was consistent among subjects and encapsulated the aneurysm initiation sites in our dataset. To test the sensitivity of our results, CFD simulations were repeated with a second independent observer virtually removing the aneurysms and with a 20 % higher flow rate at the inlet. We found that branches harboring aneurysms were characterized by high WSS and high WSS gradients. Among all assessed variables, the aneurysm initiation site most consistently coincided with peaks of temporal variation in the WSS magnitude.

  13. Impact of wall shear stress on initial bacterial adhesion in rotating annular reactor

    PubMed Central

    Saur, Thibaut; Morin, Emilie; Habouzit, Frédéric; Bernet, Nicolas

    2017-01-01

    The objective of this study was to investigate the bacterial adhesion under different wall shear stresses in turbulent flow and using a diverse bacterial consortium. A better understanding of the mechanisms governing microbial adhesion can be useful in diverse domains such as industrial processes, medical fields or environmental biotechnologies. The impact of wall shear stress—four values ranging from 0.09 to 7.3 Pa on polypropylene (PP) and polyvinyl chloride (PVC)—was carried out in rotating annular reactors to evaluate the adhesion in terms of morphological and microbiological structures. A diverse inoculum consisting of activated sludge was used. Epifluorescence microscopy was used to quantitatively and qualitatively characterize the adhesion. Attached bacterial communities were assessed by molecular fingerprinting profiles (CE-SSCP). It has been demonstrated that wall shear stress had a strong impact on both quantitative and qualitative aspects of the bacterial adhesion. ANOVA tests also demonstrated the significant impact of wall shear stress on all three tested morphological parameters (surface coverage, number of objects and size of objects) (p-values < 2.10−16). High wall shear stresses increased the quantity of attached bacteria but also altered their spatial distribution on the substratum surface. As the shear increased, aggregates or clusters appeared and their size grew when increasing the shears. Concerning the microbiological composition, the adhered bacterial communities changed gradually with the applied shear. PMID:28207869

  14. Endothelial Dysfunction in Diabetes Mellitus: Possible Involvement of Endoplasmic Reticulum Stress?

    PubMed Central

    Basha, Basma; Samuel, Samson Mathews; Triggle, Chris R.; Ding, Hong

    2012-01-01

    The vascular complications of diabetes mellitus impose a huge burden on the management of this disease. The higher incidence of cardiovascular complications and the unfavorable prognosis among diabetic individuals who develop such complications have been correlated to the hyperglycemia-induced oxidative stress and associated endothelial dysfunction. Although antioxidants may be considered as effective therapeutic agents to relieve oxidative stress and protect the endothelium, recent clinical trials involving these agents have shown limited therapeutic efficacy in this regard. In the recent past experimental evidence suggest that endoplasmic reticulum (ER) stress in the endothelial cells might be an important contributor to diabetes-related vascular complications. The current paper contemplates the possibility of the involvement of ER stress in endothelial dysfunction and diabetes-associated vascular complications. PMID:22474423

  15. Endothelial dysfunction in diabetes mellitus: possible involvement of endoplasmic reticulum stress?

    PubMed

    Basha, Basma; Samuel, Samson Mathews; Triggle, Chris R; Ding, Hong

    2012-01-01

    The vascular complications of diabetes mellitus impose a huge burden on the management of this disease. The higher incidence of cardiovascular complications and the unfavorable prognosis among diabetic individuals who develop such complications have been correlated to the hyperglycemia-induced oxidative stress and associated endothelial dysfunction. Although antioxidants may be considered as effective therapeutic agents to relieve oxidative stress and protect the endothelium, recent clinical trials involving these agents have shown limited therapeutic efficacy in this regard. In the recent past experimental evidence suggest that endoplasmic reticulum (ER) stress in the endothelial cells might be an important contributor to diabetes-related vascular complications. The current paper contemplates the possibility of the involvement of ER stress in endothelial dysfunction and diabetes-associated vascular complications.

  16. Torsional bridge setup for the characterization of integrated circuits and microsensors under mechanical shear stress.

    PubMed

    Herrmann, M; Gieschke, P; Ruther, P; Paul, O

    2011-12-01

    We present a torsional bridge setup for the electro-mechanical characterization of devices integrated in the surface of silicon beams under mechanical in-plane shear stress. It is based on the application of a torsional moment to the longitudinal axis of the silicon beams, which results in a homogeneous in-plane shear stress in the beam surface. The safely applicable shear stresses span the range of ±50 MPa. Thanks to a specially designed clamping mechanism, the unintended normal stress typically stays below 2.5% of the applied shear stress. An analytical model is presented to compute the induced shear stress. Numerical computations verify the analytical results and show that the homogeneity of the shear stress is very high on the beam surface in the region of interest. Measurements with piezoresistive microsensors fabricated using a complementary metal-oxide-semiconductor process show an excellent agreement with both the computational results and comparative measurements performed on a four-point bending bridge. The electrical connection to the silicon beam is performed with standard bond wires. This ensures that minimal forces are applied to the beam by the electrical interconnection to the external instrumentation and that devices with arbitrary bond pad layout can be inserted into the setup.

  17. Gyrokinetic simulation of momentum transport with residual stress from diamagnetic level velocity shears

    SciTech Connect

    Waltz, R. E.; Staebler, G. M.; Solomon, W. M.

    2011-04-15

    Residual stress refers to the remaining toroidal angular momentum (TAM) flux (divided by major radius) when the shear in the equilibrium fluid toroidal velocity (and the velocity itself) vanishes. Previously [Waltz et al., Phys. Plasmas 14, 122507 (2007); errata 16, 079902 (2009)], we demonstrated with GYRO [Candy and Waltz, J. Comp. Phys. 186, 545 (2003)] gyrokinetic simulations that TAM pinching from (ion pressure gradient supported or diamagnetic level) equilibrium ExB velocity shear could provide some of the residual stress needed to support spontaneous toroidal rotation against normal diffusive loss. Here we show that diamagnetic level shear in the intrinsic drift wave velocities (or ''profile shear'' in the ion and electron density and temperature gradients) provides a comparable residual stress. The individual signed contributions of these small (rho-star level) ExB and profile velocity shear rates to the turbulence level and (rho-star squared) ion energy transport stabilization are additive if the rates are of the same sign. However because of the additive stabilization effect, the contributions to the small (rho-star cubed) residual stress is not always simply additive. If the rates differ in sign, the residual stress from one can buck out that from the other (and in some cases reduce the stabilization.) The residual stress from these diamagnetic velocity shear rates is quantified by the ratio of TAM flow to ion energy (power) flow (M/P) in a global GYRO core simulation of a ''null'' toroidal rotation DIII-D [Mahdavi and Luxon, Fusion Sci. Technol. 48, 2 (2005)] discharge by matching M/P profiles within experimental uncertainty. Comparison of global GYRO (ion and electron energy as well as particle) transport flow balance simulations of TAM transport flow in a high-rotation DIII-D L-mode quantifies and isolates the ExB shear and parallel velocity (Coriolis force) pinching components from the larger ''diffusive'' parallel velocity shear driven component and

  18. Response of human endothelial cells to oxidative stress on Ti6Al4V alloy.

    PubMed

    Tsaryk, Roman; Kalbacova, Marie; Hempel, Ute; Scharnweber, Dieter; Unger, Ronald E; Dieter, Peter; Kirkpatrick, C James; Peters, Kirsten

    2007-02-01

    Titanium and its alloys are amongst the most frequently used materials in bone and dental implantology. The good biocompatibility of titanium(-alloys) is attributed to the formation of a titanium oxide layer on the implant surface. However, implant failures do occur and this appears to be due to titanium corrosion. Thus, cells participating in the wound healing processes around an implanted material, among them endothelial cells, might be subjected to reactive oxygen species (ROS) formed by electrochemical processes during titanium corrosion. Therefore, we studied the response of endothelial cells grown on Ti6Al4V alloy to H(2)O(2) and compared this with the response of endothelial cells grown on cell culture polystyrene (PS). We could show that although the cell number was the same on both surfaces, metabolic activity of endothelial cells grown on Ti6Al4V alloy was reduced compared to the cells on PS and further decreased following prototypic oxidative stress (H(2)O(2)-treatment). The analysis of H(2)O(2)-induced oxidative stress showed a higher ROS formation in endothelial cells on Ti6Al4V than on PS. This correlated with the depletion of reduced glutathione (GSH) in endothelial cells grown on Ti6Al4V surfaces and indicated permanent oxidative stress. Thus, endothelial cells in direct contact with Ti6Al4V showed signs of oxidative stress and higher impairment of cell vitality after an additional oxidative stress. However, the exact nature of the agent of oxidative stress generated from Ti6Al4V remains unclear and requires further investigation.

  19. A High shear stress segment along the San Andreas Fault: Inferences based on near-field stress direction and stress magnitude observations in the Carrizo Plain Area

    SciTech Connect

    Castillo, D. A.,; Younker, L.W.

    1997-01-30

    Nearly 200 new in-situ determinations of stress directions and stress magnitudes near the Carrizo plain segment of the San Andreas fault indicate a marked change in stress state occurring within 20 km of this principal transform plate boundary. A natural consequence of this stress transition is that if the observed near-field ``fault-oblique`` stress directions are representative of the fault stress state, the Mohr-Coulomb shear stresses resolved on San Andreas sub-parallel planes are substantially greater than previously inferred based on fault-normal compression. Although the directional stress data and near-hydrostatic pore pressures, which exist within 15 km of the fault, support a high shear stress environment near the fault, appealing to elevated pore pressures in the fault zone (Byerlee-Rice Model) merely enhances the likelihood of shear failure. These near-field stress observations raise important questions regarding what previous stress observations have actually been measuring. The ``fault-normal`` stress direction measured out to 70 km from the fault can be interpreted as representing a comparable depth average shear strength of the principal plate boundary. Stress measurements closer to the fault reflect a shallower depth-average representation of the fault zone shear strength. If this is true, only stress observations at fault distances comparable to the seismogenic depth will be representative of the fault zone shear strength. This is consistent with results from dislocation monitoring where there is pronounced shear stress accumulation out to 20 km of the fault as a result of aseismic slip within the lower crust loading the upper locked section. Beyond about 20 km, the shear stress resolved on San Andreas fault-parallel planes becomes negligible. 65 refs., 15 figs.

  20. Quantification of Interfibrillar Shear Stress in Aligned Soft Collagenous Tissues via Notch Tension Testing

    PubMed Central

    Szczesny, Spencer E.; Caplan, Jeffrey L.; Pedersen, Pal; Elliott, Dawn M.

    2015-01-01

    The mechanical function of soft collagenous tissues is largely determined by their hierarchical organization of collagen molecules. While collagen fibrils are believed to be discontinuous and transfer load through shearing of the interfibrillar matrix, interfibrillar shear stresses have never been quantified. Scaling traditional shear testing procedures down to the fibrillar length scale is impractical and would introduce substantial artifacts. Here, through the use of a novel microscopic variation of notch tension testing, we explicitly demonstrate the existence of interfibrillar shear stresses within tendon fascicles and provide the first measurement of their magnitude. Axial stress gradients along the sample length generated by notch tension testing were measured and used to calculate a value of 32 kPa for the interfibrillar shear stress. This estimate is comparable to the interfibrillar shear stress predicted by previous multiscale modeling of tendon fascicles, which supports the hypothesis that fibrils are discontinuous and transmit load through interfibrillar shear. This information regarding the structure-function relationships of tendon and other soft collagenous tissues is necessary to identify potential causes for tissue impairment with degeneration and provide the foundation for developing regenerative repair strategies or engineering biomaterials for tissue replacement. PMID:26469396

  1. Quantification of Interfibrillar Shear Stress in Aligned Soft Collagenous Tissues via Notch Tension Testing

    NASA Astrophysics Data System (ADS)

    Szczesny, Spencer E.; Caplan, Jeffrey L.; Pedersen, Pal; Elliott, Dawn M.

    2015-10-01

    The mechanical function of soft collagenous tissues is largely determined by their hierarchical organization of collagen molecules. While collagen fibrils are believed to be discontinuous and transfer load through shearing of the interfibrillar matrix, interfibrillar shear stresses have never been quantified. Scaling traditional shear testing procedures down to the fibrillar length scale is impractical and would introduce substantial artifacts. Here, through the use of a novel microscopic variation of notch tension testing, we explicitly demonstrate the existence of interfibrillar shear stresses within tendon fascicles and provide the first measurement of their magnitude. Axial stress gradients along the sample length generated by notch tension testing were measured and used to calculate a value of 32 kPa for the interfibrillar shear stress. This estimate is comparable to the interfibrillar shear stress predicted by previous multiscale modeling of tendon fascicles, which supports the hypothesis that fibrils are discontinuous and transmit load through interfibrillar shear. This information regarding the structure-function relationships of tendon and other soft collagenous tissues is necessary to identify potential causes for tissue impairment with degeneration and provide the foundation for developing regenerative repair strategies or engineering biomaterials for tissue replacement.

  2. Panoramic diagnostics of shear stresses on the channel wall with a step using the liquid crystals

    NASA Astrophysics Data System (ADS)

    Zharkova, G. M.; Kovrizhina, V. N.; Petrov, A. P.; Pod'yachev, S. P.

    2016-11-01

    Measurements results on the shear stresses of surface friction by means of thin-film coatings based on cholesteric liquid crystals and specialized software for digital processing of experimental video are presented in the paper. The calibration dependencies of shear stress relative to the hue and azimuth angle as well as shear stress spatial distribution at subsonic turbulent flow ( V ∝ = 84 m/s) around a step, trapezoidal in plane (Reynolds number calculated for step height h, Re h = 2.57•104), with a base angle of 46° were derived for two geometries of experiment. The experiments demonstrated high sensitivity of liquid crystals to rearrangement of the near-wall flow structure and possibility to obtain quantitative data about mean shear stress levels.

  3. Estimation of turbulent shear stress in free jets: application to valvular regurgitation.

    PubMed

    Winoto, S H; Shah, D A; Liu, H

    1996-01-01

    In an attempt to better assess the severity of valvular regurgitation, an in-vitro experiment has been conducted to estimate turbulent shear stress levels within free jets issuing from different orifice shapes and sizes by means of hot-wire anemometry. On the basis of the measured mean velocities and the jet profiles, the distributions of the normalized kinematic turbulent shear stress (uv/Um2) were estimated for different jets by using an equation available for self-preserving circular jet. The results indicate that the equation can estimate the distributions of uv/Um2 independent of the orifice shape and Reynolds number of the jet. For the range of Reynolds numbers considered, the estimation of maximum turbulent shear stress inferred from these distributions suggests that the critical shear stress level of approximately 200 N/m2, corresponding to destruction of blood cells, is exceeded for typical blood flow velocity of 5 m/s at the valvular lesion.

  4. An equilibrium method for prediction of transverse shear stresses in a thick laminated plate

    NASA Technical Reports Server (NTRS)

    Chaudhuri, R. Z.

    1986-01-01

    First two equations of equilibrium are utilized to compute the transverse shear stress variation through thickness of a thick laminated plate after in-plane stresses have been computed using an assumed quadratic displacement triangular element based on transverse inextensibility and layerwise constant shear angle theory (LCST). Centroid of the triangle is the point of exceptional accuracy for transverse shear stresses. Numerical results indicate close agreement with elasticity theory. An interesting comparison between the present theory and that based on assumed stress hybrid finite element approach suggests that the latter does not satisfy the condition of free normal traction at the edge. Comparison with numerical results obtained by using constant shear angle theory suggests that LCST is close to the elasticity solution while the CST is closer to classical (CLT) solution. It is also demonstrated that the reduced integration gives faster convergence when the present theory is applied to a thin plate.

  5. The Micro-Pillar Shear-Stress Sensor MPS3 for Turbulent Flow

    PubMed Central

    Große, Sebastian; Schröder, Wolfgang

    2009-01-01

    Wall-shear stress results from the relative motion of a fluid over a body surface as a consequence of the no-slip condition of the fluid in the vicinity of the wall. To determine the two-dimensional wall-shear stress distribution is of utter importance in theoretical and applied turbulence research. In this article, characteristics of the Micro-Pillar Shear-Stress Sensor MPS3, which has been shown to offer the potential to measure the two-directional dynamic wall-shear stress distribution in turbulent flows, will be summarized. After a brief general description of the sensor concept, material characteristics, possible sensor-structure related error sources, various sensitivity and distinct sensor performance aspects will be addressed. Especially, pressure-sensitivity related aspects will be discussed. This discussion will serve as ‘design rules’ for possible new fields of applications of the sensor technology. PMID:22574010

  6. Theory to predict shear stress on cells in turbulent blood flow.

    PubMed

    Morshed, Khandakar Niaz; Bark, David; Forleo, Marcio; Dasi, Lakshmi Prasad

    2014-01-01

    Shear stress on blood cells and platelets transported in a turbulent flow dictates the fate and biological activity of these cells. We present a theoretical link between energy dissipation in turbulent flows to the shear stress that cells experience and show that for the case of physiological turbulent blood flow: (a) the Newtonian assumption is valid, (b) turbulent eddies are universal for the most complex of blood flow problems, and (c) shear stress distribution on turbulent blood flows is possibly universal. Further we resolve a long standing inconsistency in hemolysis between laminar and turbulent flow using the theoretical framework. This work demonstrates that energy dissipation as opposed to bulk shear stress in laminar or turbulent blood flow dictates local mechanical environment of blood cells and platelets universally.

  7. Wall shear stress measurement in blade end-wall corner region

    NASA Technical Reports Server (NTRS)

    Bhargava, R.; Raj, R.; Boldman, D. R.

    1987-01-01

    The magnitude and the direction of wall shear stress and surface pressure in the blade end-wall corner region were investigated. The measurements were obtained on a specially designed Preston tube, the tip of which could be concentrically rotated about its axis of rotation at the measurement location. The magnitude of wall shear stress in the vicinity of the corner was observed to increase significantly (170 percent) compared to its far-upstream value; the increase was consistently higher on the blade surface compared to the value on the plate surface of the blade end-wall corner. On both surfaces in the blade end-wall corner, the variation of the wall shear stress direction was found to be more predominant in the vicinity of the blade leading-edge location. The trend of the measured wall shear stress direction showed good agreement with the limiting streamline directions obtained from the flow visualization studies.

  8. Disturbed flow mediated modulation of shear forces on endothelial plane: A proposed model for studying endothelium around atherosclerotic plaques

    PubMed Central

    Balaguru, Uma Maheswari; Sundaresan, Lakshmikirupa; Manivannan, Jeganathan; Majunathan, Reji; Mani, Krishnapriya; Swaminathan, Akila; Venkatesan, Saravanakumar; Kasiviswanathan, Dharanibalan; Chatterjee, Suvro

    2016-01-01

    Disturbed fluid flow or modulated shear stress is associated with vascular conditions such as atherosclerosis, thrombosis, and aneurysm. In vitro simulation of the fluid flow around the plaque micro-environment remains a challenging approach. Currently available models have limitations such as complications in protocols, high cost, incompetence of co-culture and not being suitable for massive expression studies. Hence, the present study aimed to develop a simple, versatile model based on Computational Fluid Dynamics (CFD) simulation. Current observations of CFD have shown the regions of modulated shear stress by the disturbed fluid flow. To execute and validate the model in real sense, cell morphology, cytoskeletal arrangement, cell death, reactive oxygen species (ROS) profile, nitric oxide production and disturbed flow markers under the above condition were assessed. Endothelium at disturbed flow region which had been exposed to low shear stress and swirling flow pattern showed morphological and expression similarities with the pathological disturbed flow environment reported previously. Altogether, the proposed model can serve as a platform to simulate the real time micro-environment of disturbed flow associated with eccentric plaque shapes and the possibilities of studying its downstream events. PMID:27255968

  9. Disturbed flow mediated modulation of shear forces on endothelial plane: A proposed model for studying endothelium around atherosclerotic plaques

    NASA Astrophysics Data System (ADS)

    Balaguru, Uma Maheswari; Sundaresan, Lakshmikirupa; Manivannan, Jeganathan; Majunathan, Reji; Mani, Krishnapriya; Swaminathan, Akila; Venkatesan, Saravanakumar; Kasiviswanathan, Dharanibalan; Chatterjee, Suvro

    2016-06-01

    Disturbed fluid flow or modulated shear stress is associated with vascular conditions such as atherosclerosis, thrombosis, and aneurysm. In vitro simulation of the fluid flow around the plaque micro-environment remains a challenging approach. Currently available models have limitations such as complications in protocols, high cost, incompetence of co-culture and not being suitable for massive expression studies. Hence, the present study aimed to develop a simple, versatile model based on Computational Fluid Dynamics (CFD) simulation. Current observations of CFD have shown the regions of modulated shear stress by the disturbed fluid flow. To execute and validate the model in real sense, cell morphology, cytoskeletal arrangement, cell death, reactive oxygen species (ROS) profile, nitric oxide production and disturbed flow markers under the above condition were assessed. Endothelium at disturbed flow region which had been exposed to low shear stress and swirling flow pattern showed morphological and expression similarities with the pathological disturbed flow environment reported previously. Altogether, the proposed model can serve as a platform to simulate the real time micro-environment of disturbed flow associated with eccentric plaque shapes and the possibilities of studying its downstream events.

  10. Influence of polymer charge on the shear yield stress of silica aggregated with adsorbed cationic polymers.

    PubMed

    Zhou, Ying; Yu, Hai; Wanless, Erica J; Jameson, Graeme J; Franks, George V

    2009-08-15

    Flocs were produced by adding three cationic polymers (10% charge density, 3.0x10(5) g/mol molecular weight; 40% charge density, 1.1x10(5) g/mol molecular weight; and 100% charge density, 1.2x10(5) g/mol molecular weight) to 90 nm diameter silica particles. The shear yield stresses of the consolidated sediment beds from settled and centrifuged flocs were determined via the vane technique. The polymer charge density plays an important role in influencing the shear yield stresses of sediment beds. The shear yield stresses of sediment beds from flocs induced by the 10% charged polymer were observed to increase with an increase in polymer dose, initial solid concentration and background electrolyte concentration at all volume fractions. In comparison, polymer dose has a marginal effect on the shear yield stresses of sediment beds from flocs induced by the 40% and 100% charged polymers. The shear yield stresses of sediments from flocs induced by the 40% charged polymer are independent of salt concentration whereas the addition of salt decreases the shear yield stresses of sediments from flocs induced by the 100% charged polymer. When flocculated at the optimum dose for each polymer (12 mg/g silica for the 10% charged polymer at 0.03 M NaCl, 12 mg/g for 40% and 2 mg/g for 100%), shear yield stress increases as polymer charge increases. The effects observed are related to the flocculation mechanism (bridging, patch attraction or charge neutralisation) and the magnitude of the adhesive force. Comparison of shear and compressive yield stresses show that the network is only slightly weaker in shear than in compression. This is different than many other systems (mainly salt and pH coagulation) which have shear yield stress much less than compressive yield stress. The existing models relating the power law exponent of the volume fraction dependence of the shear yield stress to the network fractal structure are not satisfactory to predict all the experimental behaviour.

  11. Liposomal drug deposits in poly(dopamine) coatings: effect of their composition, cell type, uptake pathway considerations, and shear stress.

    PubMed

    Lynge, Martin E; Fernandez-Medina, Marina; Postma, Almar; Städler, Brigitte

    2014-12-01

    Implantable devices equipped with coatings which have the ability to carry and deliver active compounds are of great interest. We report the assembly of liposome-containing poly(dopamine) films, and their interaction with adhering cells. The liposome composition is varied by adding lipophilic dopamine-conjugates and charged lipids. The cell mean fluorescence (CMF) of adhering cells due to the internalization of fluorescent cargo is found to be similar for coatings with the lipophilic-dopamine conjugates, while the charge affects the amount and location of the internalized cargo. The uptake mechanism for cargo by myoblasts using chemical inhibitors is found to be dependent on the used type of liposome. The CMF is significantly reduced for endothelial cells adhering to coatings with applied shear stress.

  12. Activation and shedding of platelet glycoprotein IIb/IIIa under non-physiological shear stress.

    PubMed

    Chen, Zengsheng; Mondal, Nandan K; Ding, Jun; Koenig, Steven C; Slaughter, Mark S; Griffith, Bartley P; Wu, Zhongjun J

    2015-11-01

    The purpose of this study was to investigate the influence of non-physiological high shear stress on activation and shedding of platelet GP IIb/IIIa receptors. The healthy donor blood was exposed to three levels of high shear stresses (25, 75, 125 Pa) from the physiological to non-physiological status with three short exposure time (0.05, 0.5, 1.5 s), created by a specific blood shearing system. The activation and shedding of the platelet GPIIb/IIIa were analyzed using flow cytometry and enzyme-linked immunosorbent assay. In addition, platelet P-selectin expression of sheared blood, which is a marker for activated platelets, was also analyzed. The results from the present study showed that the number of activated platelets, as indicated by the surface GPIIb/IIIa activation and P-selectin expression, increased with increasing the shear stress level and exposure time. However, the mean fluorescence of GPIIb/IIIa on the platelet surface, decreased with increasing the shear stress level and exposure time. The reduction of GPIIb/IIIa on the platelet surface was further proved by the reduction of further activated platelet GPIIb/IIIa surface expression induced by ADP and the increase in GPIIb/IIIa concentration in microparticle-free plasma with increasing the applied shear stress and exposure time. It is clear that non-physiological shear stress induce a paradoxical phenomenon, in which both activation and shedding of the GPIIb/IIIa on the platelet surface occur simultaneously. This study may offer a new perspective to explain the reason of both increased thrombosis and bleeding events in patients implanted with high shear blood-contacting medical devices.

  13. ESTIMATION OF SHEAR STRESS WORKING ON SUBMERGED HOLLOW FIBRE MEMBRANE BY CFD METHOD IN MBRs

    NASA Astrophysics Data System (ADS)

    Zaw, Hlwan Moe; Li, Tairi; Nagaoka, Hiroshi

    This study was conducted to evaluate shear stress working on submerged hollow fibre membrane by CFD (Computation Fluid Dynamics) method in MBRs. Shear stress on hollow fibre membrane caused by aeration was measured directly using a two-direction load sensor. The measurement of water-phase flow velocity was done also by using laser doppler velocimeter. It was confirmed that the shear stress was possible to be evaluated from the water-phase flow velocityby the result of comparison of time average shear stress actually measured with one hollow fibre membrane and the one calculated by the water-phase flow velocity. In the estimation of the water-phase flow velocity using the CFD method, time average water-phase flow velocity estimated by consideration of the fluid resistance of the membrane module nearly coincided with the measured values, and it was shown that it was possible to be estimated also within the membrane module. Moreover, the measured shear stress and drag force well coincided with the values calculated from the estimated water-phase flow velocity outside of membrane module and in the center of membrane module, and it was suggested that the shear stress on the hollow fibre membrane could be estimated by the CFD method in MBRs.

  14. Transverse shear stresses and their sensitivity coefficients in multilayered composite panels

    NASA Technical Reports Server (NTRS)

    Noor, Ahmed K.; Kim, Yong H.; Peters, Jeanne M.

    1994-01-01

    A computational procedure is presented for the accurate determination of transverse shear stresses and their sensitivity coefficients in flat multilayered composite panels subjected to mechanical and thermal loads. The sensitivity coefficients measure the sensitivity of the transverse shear stresses to variations in the different lamination and material parameters of the panel. The panel is discretized by using either a three-field mixed finite element model based on a two-dimensional first- order shear deformation plate theory or a two-field degenerate solid element with each of the displacement components having a linear variation throughout the thickness of the laminate. The evaluation of transverse shear stresses can be conveniently divided into two phases. The first phase consists of using a superconvergent recovery technique for evaluating the in-plane stresses in the different layers. In the second phase, the transverse shear stresses are evaluated by using piecewise integration, in the thickness direction, of the three-dimensional equilibrium equations. The same procedure is used for evaluating the sensitivity coefficients of the transverse shear stresses. The effectiveness of the computational procedure is demonstrated by means of numerical examples of multilayered cross-ply panels subjected to transverse loading, uniform temperature change, and uniform temperature gradient through the thickness of the panel. In each case the standard of the comparison is taken to be the exact solution of the three dimensional thermoelasticity equations of the panel.

  15. Orbital fluid shear stress promotes osteoblast metabolism, proliferation and alkaline phosphates activity in vitro.

    PubMed

    Aisha, M D; Nor-Ashikin, M N K; Sharaniza, A B R; Nawawi, H; Froemming, G R A

    2015-09-10

    Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250 RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases.

  16. Application of Entropy Concept for Shear Stress Distribution in Laminar Pipe Flow

    NASA Astrophysics Data System (ADS)

    Choo, Yeon Moon; Choo, Tai Ho; Jung, Donghwi; Seon, Yun Gwan; Kim, Joong Hoon

    2016-04-01

    In the river fluid mechanics, shear stress is calculated from frictional force caused by viscosity and fluctuating velocity. Traditional shear stress distribution equations have been widely used because of their simplicity. However, they have a critical limitation of requiring energy gradient which is generally difficult to estimate in practice. Especially, measuring velocity/velocity gradient on the boundary layer is difficult in practice. It requires point velocity throughout the entire cross section to calculate velocity gradient. This study proposes shear stress distribution equations for laminar flow based on entropy theory using mean velocity and entropy coefficient. The proposed equations are demonstrated and compared with measured shear stress distribution using Nikuradse's data. Results showed that the coefficient of determination is around 0.99 indicating that the proposed method well describes the true shear stress distribution. Therefore, it was proved that shear stress distribution can be easily and accurately estimated by using the proposed equations. (This research was supported by a gran(13AWMP-B066744-01) from Advanced Water Management Research Program funded by Ministry of Land, Infrastructure and Transport of Korean Government)

  17. Doppler optical coherence tomography imaging of local fluid flow and shear stress within microporous scaffolds

    NASA Astrophysics Data System (ADS)

    Jia, Yali; Bagnaninchi, Pierre O.; Yang, Ying; Haj, Alicia El; Hinds, Monica T.; Kirkpatrick, Sean J.; Wang, Ruikang K.

    2009-05-01

    Establishing a relationship between perfusion rate and fluid shear stress in a 3D cell culture environment is an ongoing and challenging task faced by tissue engineers. We explore Doppler optical coherence tomography (DOCT) as a potential imaging tool for in situ monitoring of local fluid flow profiles inside porous chitosan scaffolds. From the measured fluid flow profiles, the fluid shear stresses are evaluated. We examine the localized fluid flow and shear stress within low- and high-porosity chitosan scaffolds, which are subjected to a constant input flow rate of 0.5 ml.min-1. The DOCT results show that the behavior of the fluid flow and shear stress in micropores is strongly dependent on the micropore interconnectivity, porosity, and size of pores within the scaffold. For low-porosity and high-porosity chitosan scaffolds examined, the measured local fluid flow and shear stress varied from micropore to micropore, with a mean shear stress of 0.49+/-0.3 dyn.cm-2 and 0.38+/-0.2 dyn.cm-2, respectively. In addition, we show that the scaffold's porosity and interconnectivity can be quantified by combining analyses of the 3D structural and flow images obtained from DOCT.

  18. Using two soft computing methods to predict wall and bed shear stress in smooth rectangular channels

    NASA Astrophysics Data System (ADS)

    Khozani, Zohreh Sheikh; Bonakdari, Hossein; Zaji, Amir Hossein

    2017-03-01

    Two soft computing methods were extended in order to predict the mean wall and bed shear stress in open channels. The genetic programming (GP) and Genetic Algorithm Artificial Neural Network (GAA) were investigated to determine the accuracy of these models in estimating wall and bed shear stress. The GP and GAA model results were compared in terms of testing dataset in order to find the best model. In modeling both bed and wall shear stress, the GP model performed better with RMSE of 0.0264 and 0.0185, respectively. Then both proposed models were compared with equations for rectangular open channels, trapezoidal channels and ducts. According to the results, the proposed models performed the best in predicting wall and bed shear stress in smooth rectangular channels. The obtained equation for rectangular channels could estimate values closer to experimental data, but the equations for ducts had poor, inaccurate results in predicting wall and bed shear stress. The equation presented for trapezoidal channels did not have acceptable accuracy in predicting wall and bed shear stress either.

  19. Effect of Varying Fluid Shear Stress on Cancer Stem Cell Viability & Protein Expression

    NASA Astrophysics Data System (ADS)

    Domier, Ria; Kim, Yonghyun; Dozier, David; Triantafillu, Ursula

    2013-11-01

    Cancer stem cells cultured in vitro in stirred bioreactors are exposed to shear stress. By observing the effect of shear stress on cancer stem cell viability, laboratory cell growth could be optimized. In addition, metastasized cancer stem cells in vivo are naturally exposed to shear stress, a factor influencing stem cell differentiation, while circulating in the bloodstream. Changes in protein expression after exposure to shear stress could allow for identification and targeting of circulating cancer cells. In this study, blood flow through capillaries was simulated by using a syringe pump to inject suspensions of Kasumi-1 leukemia stem cells into model blood vessels composed of PEEK tubing 125 microns in diameter. The Hagen-Poisseuille equation was used to solve for operating flow rates based on specified amounts of shear stress. After exposure, cell counts and viabilities were observed using an optical microscope and proteins were analyzed using Western blotting. It was observed that at a one minute exposure to stress, cell viability increased as the amount of shear was increased from 10 to 60 dynes per square centimeter. Results from this research are applicable to optimization of large-scale stem cell growth in bioreactors as well as to the design of targeted cancer therapies. Funding from NSF REU grant #1062611 is gratefully acknowledged.

  20. RhoA and Membrane Fluidity Mediates the Spatially Polarized Src/FAK Activation in Response to Shear Stress

    PubMed Central

    Liu, Bo; Lu, Shaoying; Hu, Ying-li; Liao, Xiaoling; Ouyang, Mingxing; Wang, Yingxiao

    2014-01-01

    While Src plays crucial roles in shear stress-induced cellular processes, little is known on the spatiotemporal pattern of high shear stress (HSS)-induced Src activation. HSS (65 dyn/cm2) was applied on bovine aortic endothelial cells to visualize the dynamic Src activation at subcellular levels utilizing a membrane-targeted Src biosensor (Kras-Src) based on fluorescence resonance energy transfer (FRET). A polarized Src activation was observed with higher activity at the side facing the flow, which was enhanced by a cytochalasin D-mediated disruption of actin filaments but inhibited by a benzyl alcohol-mediated enhancement of membrane fluidity. Further experiments revealed that HSS decreased RhoA activity, with a constitutively active RhoA mutant inhibiting while a negative RhoA mutant enhancing the HSS-induced Src polarity. Cytochalasin D can restore the polarity in cells expressing the active RhoA mutant. Further results indicate that HSS stimulates FAK activation with a spatial polarity similar to Src. The inhibition of Src by PP1, as well as the perturbation of RhoA activity and membrane fluidity, can block this HSS-induced FAK polarity. These results indicate that the HSS-induced Src and subsequently FAK polarity depends on the coordination between intracellular tension distribution regulated by RhoA, its related actin structures and the plasma membrane fluidity. PMID:25387906

  1. Influence of high deformation rate, brain region, transverse compression, and specimen size on rat brain shear stress morphology and magnitude.

    PubMed

    Haslach, Henry W; Gipple, Jenna M; Leahy, Lauren N

    2017-01-26

    An external mechanical insult to the brain, such as a blast, may create internal stress and deformation waves, which have shear and longitudinal components that can induce combined shear and compression of the brain tissue. To isolate the consequences of such interactions for the shear stress and to investigate the role of the extracellular fluid in the mechanical response, translational shear stretch at 10/s, 60/s, and 100/s translational shear rates under either 0% or 33% fixed transverse compression is applied without preconditioning to rat brain specimens. The specimens from the cerebrum, the cerebellum grey matter, and the brainstem white matter are nearly the full length of their respective regions. The translational shear stress response to translational shear deformation is characterized by the effect that each of four factors, high deformation rate, brain region, transverse compression, and specimen size, have on the shear stress magnitude averaged over ten specimens for each combination of factors. Increasing the deformation rate increases the magnitude of the shear stress at a given translational shear stretch, and as tested by ANOVAs so does applying transverse fixed compression of 33% of the thickness. The stress magnitude differs by the region that is the specimen source: cerebrum, cerebellum or brainstem. The magnitude of the shear stress response at a given deformation rate and stretch depends on the specimen length, called a specimen size effect. Surprisingly, under no compression a shorter length specimen requires more shear stress, but under 33% compression a shorter length specimen requires less shear stress, to meet a required shear deformation rate. The shear specimen size effect calls into question the applicability of the classical shear stress definition to hydrated soft biological tissue.

  2. Experimental research of mechanical behavior of porcine brain tissue under rotational shear stress.

    PubMed

    Li, Gang; Zhang, Jianhua; Wang, Kan; Wang, Mingyu; Gao, Changqing; Ma, Chao

    2016-04-01

    The objective of this paper is to investigate mechanical behavior of porcine brain tissue with a series of rotational shear stress control experiments. To this end, several experiments including stress sweep tests, frequency sweep tests and quasi-static creep tests were designed and conducted with a standard rheometer (HAAKE RheoStress6000). The effects of the loading stress rates to mechanical properties of brain tissue were also studied in stress sweep tests. The results of stress sweep tests performed on the same brain showed that brain tissue had an obvious regional inhomogeneity and the mechanical damage occurred at the rotational shear stress of 10-15Pa. The experimental data from three different loading stress rates demonstrated that the mechanical behavior of porcine brain tissue was loading stress rate dependent. With the decrease of loading stress rate, a stiffer mechanical characteristic of brain tissue was observed and the occurrence of mechanical damage can be delayed to a higher stress. From the results of frequency sweep tests we found that brain tissue had almost completely elastic properties at high frequency area. The nonlinear creep response under the rotational shear stress of 1, 3, 5, 7 and 9Pa was shown in results of creep tests. A new nonlinear viscoelastic solid model was proposed for creep tests and matched well with the test data. Considering the regional differences, loading stress rates and test conditions effects, loss tangent tan δ in porcine brain tissue showed a high uniformity of 0.25-0.45.

  3. Analysis of shearing stress in the limited durability of bovine pericardium used as a biomaterial.

    PubMed

    Carrera San Martin, A; García Paez, J M; García Sestafe, J V; Herrero, E J; Navidad, R; Cordón, A; Castillo-Olivares, J L

    1998-02-01

    The objective of the study was to determine the shearing stress exerted by the suture thread under conditions of normal working stress. Thirty-six samples of calf pericardium, similar to that employed in the manufacture of bioprosthetic cardiac valve leaflets, were subjected to tensile testing. Prior to the trial, a continuous suture was sewn in the central zone of each sample, at a 45 degrees angle to the longest axis of the sample, using commercially-available threads (silk, Gore-Tex, Surgilene and nylon). Application of the Mohr circle for combined wear revealed that the shearing stress ranged between 2.68-fold greater (for samples sewn with silk) and 5.48-fold greater (for samples sewn with nylon) than the working tensile stress in the region of the suture. It is concluded that the shearing stress is responsible for the limited durability of sutured samples of calf pericardium prepared to simulate bioprosthetic cardiac valve leaflets.

  4. A new technique for the measurement of surface shear stress vectors using liquid crystal coatings

    NASA Technical Reports Server (NTRS)

    Reda, Daniel C.; Muratore, J. J., Jr.

    1994-01-01

    Research has recently shown that liquid crystal coating (LCC) color-change response to shear depends on both shear stress magnitude and direction. Additional research was thus conducted to extend the LCC method from a flow-visualization tool to a surface shear stress vector measurement technique. A shear-sensitive LCC was applied to a planar test surface and illuminated by white light from the normal direction. A fiber optic probe was used to capture light scattered by the LCC from a point on the centerline of a turbulent, tangential-jet flow. Both the relative shear stress magnitude and the relative in-plane view angle between the sensor and the centerline shear vector were systematically varied. A spectrophotometer was used to obtain scattered-light spectra which were used to quantify the LCC color (dominant wavelength) as a function of shear stress magnitude and direction. At any fixed shear stress magnitude, the minimum dominant wavelength was measured when the shear vector was aligned with and directed away from the observer; changes in the relative in-plane view angle to either side of this vector/observer aligned position resulted in symmetric Gaussian increases in measured dominant wavelength. Based on these results, a vector measurement methodology, involving multiple oblique-view observations of the test surface, was formulated. Under present test conditions, the measurement resolution of this technique was found to be +/- 1 deg for vector orientations and +/- 5% for vector magnitudes. An approach t o extend the present methodology to full-surface applications is proposed.

  5. Working Principle Simulations of a Dynamic ResonantWall Shear Stress Sensor Concept.

    PubMed

    Zhang, Xu; Naughton, Jonathan W; Lindberg, William R

    2008-04-17

    This paper discusses a novel dynamic resonant wall shear stress sensor concept based on an oscillating sensor operating near resonance. The interaction between the oscillating sensor surface and the fluid above it is modelled using the unsteady laminar boundary layer equations. The numerical experiment shows that the effect of the oscillating shear stress is well correlated by the Hummer number, the ratio of the steady shear force caused by the outside flow to the oscillating viscous force created by the sensor motion. The oscillating shear stress predicted by the fluid model is used in a mechanical model of the sensor to predict the sensor's dynamic motion. Static calibration curves for amplitude and frequency influences are predicted. These results agree with experimental results on some extent, and shows some expectation for further development of the dynamic resonant sensor concept.

  6. The production of turbulent stress in a shear flow by irrotational fluctuations

    NASA Technical Reports Server (NTRS)

    Gartshore, I. S.; Durbin, P. A.; Hunt, J. C. R.

    1983-01-01

    This paper examines, both theoretically and experimentally, the effect produced by irrotational fluctuations, associated with a nearby turbulent field, in a region where the turbulence is initially very low but where there is a mean shear. Calculations are based on rapid distortion theory and experiments use linearized hot wire anemometers in an open circuit wind tunnel. Turbulent shear stress is observed to grow from zero to significant values in the interaction region. The magnitude and extent of this observed shear stress agree reasonably well with predictions of the analysis, when intermittency effects are included. It is concluded that turbulent stresses can be produced by irrotational fluctuations in a region of mean shear and that this effect can be estimated using rapid distortion theory if the overall strain ratio is not large.

  7. Effect of cell size and shear stress on bacterium growth rate

    NASA Astrophysics Data System (ADS)

    Fadlallah, Hadi; Jarrahi, Mojtaba; Herbert, Éric; Peerhossaini, Hassan; PEF Team

    2015-11-01

    Effect of shear stress on the growth rate of Synechocystis and Chlamydomonas cells is studied. An experimental setup was prepared to monitor the growth rate of the microorganisms versus the shear rate inside a clean room, under atmospheric pressure and 20 °C temperature. Digital magnetic agitators are placed inside a closed chamber provided with airflow, under a continuous uniform light intensity over 4 weeks. In order to study the effect of shear stress on the growth rate, different frequencies of agitation are tested, 2 vessels filled with 150 ml of each specie were placed on different agitating system at the desired frequency. The growth rate is monitored daily by measuring the optical density and then correlate it to the cellular concentration. The PH was adjusted to 7 in order to maintain the photosynthetic activity. Furthermore, to measure the shear stress distribution, the flow velocity field was measured using PIV. Zones of high and low shear stress were identified. Results show that the growth rate is independent of the shear stress magnitude, mostly for Synechocystis, and with lower independency for Chlamydomonas depending on the cell size for each species.

  8. The Effects of Stress at Work and at Home on Inflammation and Endothelial Dysfunction

    PubMed Central

    Non, Amy L.; Rimm, Eric B.; Kawachi, Ichiro; Rewak, Marissa A.; Kubzansky, Laura D.

    2014-01-01

    This study examined whether stress at work and at home may be related to dysregulation of inflammation and endothelial function, two important contributors to the development of cardiovascular disease. In order to explore potential biological mechanisms linking stress with cardiovascular health, we investigated cross-sectional associations between stress at work and at home with an inflammation score (n's range from 406–433) and with two endothelial biomarkers (intercellular and vascular adhesion molecules, sICAM-1 and sVCAM-1; n's range from 205–235) in a cohort of healthy US male health professionals. No associations were found between stress at work or at home and inflammation. Men with high or medium levels of stress at work had significantly higher levels of sVCAM-1 (13% increase) and marginally higher levels of sICAM-1 (9% increase), relative to those reporting low stress at work, independent of health behaviors. Men with high levels of stress at home had marginally higher levels of both sVCAM-1 and sICAM-1 than those with low stress at home. While lack of findings related to inflammation are somewhat surprising, if replicated in future studies, these findings may suggest that endothelial dysfunction is an important biological mechanism linking stress at work with cardiovascular health outcomes in men. PMID:24722508

  9. Irisin improves endothelial function in type 2 diabetes through reducing oxidative/nitrative stresses.

    PubMed

    Zhu, Di; Wang, Haichang; Zhang, Jinglong; Zhang, Xiaotian; Xin, Chao; Zhang, Fuyang; Lee, Yan; Zhang, Ling; Lian, Kun; Yan, Wenjun; Ma, Xinliang; Liu, Yi; Tao, Ling

    2015-10-01

    Vascular complications are the major causes of death in patients with diabetes, and endothelial dysfunction is the earliest event in vascular complications of diabetes. It has been reported that plasma irisin level is significantly reduced in patients with type 2 diabetic patients. The present study aimed to investigate whether irisin improved endothelial function in type 2 diabetes as well as the underlying mechanisms. The type 2 diabetes model was established by feeding C57BL/6 mice with high-fat diet. The type 2 diabetic mice exhibited reduced serum irisin level and impaired endothelial function. Irisin treatment (0.5 mg/kg/d) for two weeks improved vascular function based on the evaluation of endothelium-dependent vasorelaxation and p-VASP levels. To investigate the direct endothelial protective effects of irisin, diabetic aortic segments were incubated with irisin (1 μg/ml) ex vivo. Exposure to irisin improved endothelium-dependent vasorelaxation of diabetic aortas. Mechanically, the diabetic aortic segments exhibited increased oxidative/nitrative stresses. Irisin reduced the diabetes-induced oxidative/nitrative stresses evidenced by reducing overproduction of superoxide and peroxynitrite, and down-regulation of iNOS and gp91(phox). To further investigate the protective effects of irisin on endothelial cells and the underlying mechanisms, human umbilical vein endothelial cells (HUVECs) cultured in high-glucose/high-fat (HG/HF) medium were pre-incubated with irisin. Irisin (1 μg/ml) reduced the oxidative/nitrative stresses and apoptosis induced by HG/HF in HUVECs probably via inhibiting activation of PKC-β/NADPH oxidase and NF-κB/iNOS pathways. Taken together, irisin alleviates endothelial dysfunction in type 2 diabetes partially via reducing oxidative/nitrative stresses through inhibiting signaling pathways implicating PKC-β/NADPH oxidase and NF-κB/iNOS, suggesting that irisin may be a promising molecule for the treatment of vascular complications of

  10. Orbital fluid shear stress promotes osteoblast metabolism, proliferation and alkaline phosphates activity in vitro

    SciTech Connect

    Aisha, M.D.; Nor-Ashikin, M.N.K.; Sharaniza, A.B.R.; Nawawi, H.; Froemming, G.R.A.

    2015-09-10

    Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250 RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases. - Highlights: • OFS stress transmits anabolic signals to osteoblasts. • Actin and tubulin fibers are rearranged under OFS stress. • OFS stress increases mitochondrial metabolism and proliferation. • Reduced RANKL/OPG ratio in response to OFS inhibits osteoclastogenesis. • OFS stress prevents apoptosis and stimulates ALP and OCN.

  11. Fluid shear stress stimulates phosphorylation-dependent nuclear export of HDAC5 and mediates expression of KLF2 and eNOS.

    PubMed

    Wang, Weiye; Ha, Chang Hoon; Jhun, Bong Sook; Wong, Chelsea; Jain, Mukesh K; Jin, Zheng-Gen

    2010-04-08

    Fluid shear stress generated by steady laminar blood flow protects vessels from atherosclerosis. Krüppel-like factor 2 (KLF2) and endothelial nitric oxide synthase (eNOS) are fluid shear stress-responsive genes and key mediators in flow anti-inflammatory and antiatherosclerotic actions. However, the molecular mechanisms underlying flow induction of KLF2 and eNOS remain largely unknown. Here, we show a novel role of histone deacetylase 5 (HDAC5) in flow-mediated KLF2 and eNOS expression. We found for the first time that fluid shear stress stimulated HDAC5 phosphorylation and nuclear export in endothelial cells through a calcium/calmodulin-dependent pathway. Consequently, flow induced the dissociation of HDAC5 and myocyte enhancer factor-2 (MEF2) and enhanced MEF2 transcriptional activity, which leads to expression of KLF2 and eNOS. Adenoviral overexpression of a HDAC5 phosphorylation-defective mutant (Ser259/Ser498 were replaced by Ala259/Ala498, HDAC5-S/A), which shows resistance to flow-induced nuclear export, suppressed flow-mediated MEF2 transcriptional activity and expression of KLF2 and eNOS. Importantly, HDAC5-S/A attenuated the flow-inhibitory effect on monocyte adhesion to endothelial cells. Taken together, our results reveal that phosphorylation-dependent derepression of HDAC5 mediates flow-induced KLF2 and eNOS expression as well as flow anti-inflammation, and suggest that HDAC5 could be a potential therapeutic target for the prevention of atherosclerosis.

  12. Soluble surfactants favorably modify fluid structure and wall shear stress profiles during near-occluding bubble motion in a computational model of intravascular gas embolism

    NASA Astrophysics Data System (ADS)

    Swaminathan, T. N.; Ayyaswamy, P. S.; Eckmann, D. M.

    2009-11-01

    Finite sized gas bubble motion in a blood vessel causes temporal and spatial gradients of shear stress at the endothelial cell surface lining the vessel wall as the bubble approaches the cell, moves over it and passes it by. Rapid reversals occur in the sign of the shear stress imparted to the cell surface during this motion. The sign-reversing shear is a potently coupled source of cell surface mechanical stretch, potentiating cell injury. The presence of a suitable soluble surfactant in the bulk medium considerably reduces the level of the shear stress gradients imparted to the cell surface as compared to an equivalent surfactant-free system. The bubble shape and the film thickness between the bubble and the vessel wall are also different. Furthermore, the bubble residence time near the proximity of a cell surface changes in comparison. These results based on our modeling may help explain several phenomena observed in experimental studies related to gas embolism, a significant problem in cardiac surgery and decompression sickness.

  13. Accurate prediction of wall shear stress in a stented artery: newtonian versus non-newtonian models.

    PubMed

    Mejia, Juan; Mongrain, Rosaire; Bertrand, Olivier F

    2011-07-01

    A significant amount of evidence linking wall shear stress to neointimal hyperplasia has been reported in the literature. As a result, numerical and experimental models have been created to study the influence of stent design on wall shear stress. Traditionally, blood has been assumed to behave as a Newtonian fluid, but recently that assumption has been challenged. The use of a linear model; however, can reduce computational cost, and allow the use of Newtonian fluids (e.g., glycerine and water) instead of a blood analog fluid in an experimental setup. Therefore, it is of interest whether a linear model can be used to accurately predict the wall shear stress caused by a non-Newtonian fluid such as blood within a stented arterial segment. The present work compares the resulting wall shear stress obtained using two linear and one nonlinear model under the same flow waveform. All numerical models are fully three-dimensional, transient, and incorporate a realistic stent geometry. It is shown that traditional linear models (based on blood's lowest viscosity limit, 3.5 Pa s) underestimate the wall shear stress within a stented arterial segment, which can lead to an overestimation of the risk of restenosis. The second linear model, which uses a characteristic viscosity (based on an average strain rate, 4.7 Pa s), results in higher wall shear stress levels, but which are still substantially below those of the nonlinear model. It is therefore shown that nonlinear models result in more accurate predictions of wall shear stress within a stented arterial segment.

  14. The Role of Shear Stress in Arteriovenous Fistula Maturation and Failure: A Systematic Review

    PubMed Central

    Browne, Leonard D.; Bashar, Khalid; Griffin, Philip; Kavanagh, Eamon G.; Walsh, Stewart R.; Walsh, Michael T.

    2015-01-01

    Introduction Non-maturation and post-maturation venous stenosis are the primary causes of failure within arteriovenous fistulae (AVFs). Although the exact mechanisms triggering failure remain unclear, abnormal hemodynamic profiles are thought to mediate vascular remodelling and can adversely impact on fistula patency. Aim The review aims to clarify the role of shear stress on outward remodelling during maturation and evaluate the evidence supporting theories related to the localisation and development of intimal hyperplasia within AVFs. Methods A systematic review of studies comparing remodelling data with hemodynamic data obtained from computational fluid dynamics of AVFs during and after maturation was conducted. Results Outward remodelling occurred to reduce or normalise the level of shear stress over time in fistulae with a large radius of curvature (curved) whereas shear stress was found to augment over time in fistulae with a small radius of curvature (straight) coinciding with minimal to no increases in lumen area. Although this review highlighted that there is a growing body of evidence suggesting low and oscillating shear stress may stimulate the initiation and development of intimal medial thickening within AVFs. Further lines of evidence are needed to support the disturbed flow theory and outward remodelling findings before surgical configurations and treatment strategies are optimised to conform to them. This review highlighted that variation between the time of analysis, classification of IH, resolution of simulations, data processing techniques and omission of various shear stress metrics prevented forming pooling of data amongst studies. Conclusion Standardised measurements and data processing techniques are needed to comprehensively evaluate the relationship between shear stress and intimal medial thickening. Advances in image acquisition and flow quantifications coupled with the increasing prevalence of longitudinal studies commencing from fistula

  15. Shear Stress Partitioning in Large Patches of Roughness in the Atmospheric Inertial Sublayer

    NASA Technical Reports Server (NTRS)

    Gillies, John A.; Nickling, William G.; King, James

    2007-01-01

    Drag partition measurements were made in the atmospheric inertial sublayer for six roughness configurations made up of solid elements in staggered arrays of different roughness densities. The roughness was in the form of a patch within a large open area and in the shape of an equilateral triangle with 60 m long sides. Measurements were obtained of the total shear stress (tau) acting on the surfaces, the surface shear stress on the ground between the elements (tau(sub S)) and the drag force on the elements for each roughness array. The measurements indicated that tau(sub S) quickly reduced near the leading edge of the roughness compared with tau, and a tau(sub S) minimum occurs at a normalized distance (x/h, where h is element height) of approx. -42 (downwind of the roughness leading edge is negative), then recovers to a relatively stable value. The location of the minimum appears to scale with element height and not roughness density. The force on the elements decreases exponentially with normalized downwind distance and this rate of change scales with the roughness density, with the rate of change increasing as roughness density increases. Average tau(sub S): tau values for the six roughness surfaces scale predictably as a function of roughness density and in accordance with a shear stress partitioning model. The shear stress partitioning model performed very well in predicting the amount of surface shear stress, given knowledge of the stated input parameters for these patches of roughness. As the shear stress partitioning relationship within the roughness appears to come into equilibrium faster for smaller roughness element sizes it would also appear the shear stress partitioning model can be applied with confidence for smaller patches of smaller roughness elements than those used in this experiment.

  16. Forward modeling of ice topography on Mars to infer basal shear stress conditions

    NASA Astrophysics Data System (ADS)

    Banks, M. E.; Pelletier, J. D.

    2008-01-01

    Understanding the history of ice caps on Mars could reveal important information about Martian geologic and climatic history. To do this, an ice reconstruction model is needed that operates over complex topography and can be constrained with a limited number of free parameters. In this study we developed a threshold-sliding model for ice cap morphology based on the classic model of Nye later incorporated into the models of Reeh and colleagues. We have updated the Nye-Reeh model with a new numerical algorithm. Although the model was originally developed to model perfectly plastic deformation, it is applicable to any ice body that deforms when a threshold basal shear stress is exceeded. The model requires three inputs: a digital elevation model of bed topography, a ``mask'' grid that defines the position of the ice terminus, and a function defining the threshold basal shear stress. To test the robustness of the model, the morphology of the Greenland ice sheet is reconstructed using an empirical equation between threshold basal shear stress and ice surface slope. The model is then used to reconstruct the morphology of ice draping impact craters on the margins of the south polar layered deposits using an inferred constant basal shear stress of ~0.6 bar for the majority of the examples. This inferred basal shear stress value is almost 1/3 of the average basal shear stress calculated for the Greenland ice sheet. What causes this lower basal shear stress value on Mars is unclear but could involve the strain-weakening behavior of ice.

  17. Exploring the Role of Shear Stress and Severe Turbulence in Downstream Fish Passage

    SciTech Connect

    Cada, G.; Carlson, T.; Ferguson, J.; Richmond, M.; Sale, M.

    1999-07-06

    Fish may be exposed to damaging levels of fluid shear stress and turbulence while passing through hydroelectric power plants. The generally assumed locations for such potential damage are the turbine and draft tube passages, although it is possible that fish are also injured during passage over the spillway or through sluiceways and fish bypass outfalls. Unless mitigated, fluid-induced injuries and mortality could frustrate efforts to develop advanced, fish-friendly turbines or to provide safe alternate downstream passages. The effects of shear stress and turbulence on fish are poorly understood, in part because of the difficulties in conceptualizing these phenomena, determining their magnitudes and distribution within hydroelectric systems, and then recreating them in a controlled laboratory environment. We define the fluid phenomena that are relevant to the assessment of effects on fish. The magnitudes of fluid stresses associated with man-altered aquatic environments are often considerably higher than those found in natural environments (e.g., normal river flows). However, levels of shear stresses that occur during flash floods appear to be comparable to those expected within a turbine. Past studies of the effects of shear stress on fish are of limited value, mainly because of their narrow scope and lack of instrumentation to measure velocities on appropriately small scales. A laboratory experiment to study the effects of shear stress and turbulence on fish is described.

  18. The role of wall shear stress in the assessment of right ventricle hydraulic workload.

    PubMed

    Kheyfets, Vitaly; Thirugnanasambandam, Mirunalini; Rios, Lourdes; Evans, Daniel; Smith, Triston; Schroeder, Theodore; Mueller, Jeffrey; Murali, Srinivas; Lasorda, David; Spotti, Jennifer; Finol, Ender

    2015-03-01

    Pulmonary hypertension (PH) is a devastating disease affecting approximately 15-50 people per million, with a higher incidence in women. PH mortality is mostly attributed to right ventricle (RV) failure, which results from RV hypotrophy due to an overburdened hydraulic workload. The objective of this study is to correlate wall shear stress (WSS) with hemodynamic metrics that are generally accepted as clinical indicators of RV workload and are well correlated with disease outcome. Retrospective right heart catheterization data for 20 PH patients were analyzed to derive pulmonary vascular resistance (PVR), arterial compliance (C), and an index of wave reflections (Γ). Patient-specific contrast-enhanced computed tomography chest images were used to reconstruct the individual pulmonary arterial trees up to the seventh generation. Computational fluid dynamics analyses simulating blood flow at peak systole were conducted for each vascular model to calculate WSS distributions on the endothelial surface of the pulmonary arteries. WSS was found to be decreased proportionally with elevated PVR and reduced C. Spatially averaged WSS (SAWSS) was positively correlated with PVR (R (2) = 0.66), C (R (2) = 0.73), and Γ (R (2) = 0.5) and also showed promising preliminary correlations with RV geometric characteristics. Evaluating WSS at random cross sections in the proximal vasculature (main, right, and left pulmonary arteries), the type of data that can be acquired from phase-contrast magnetic resonance imaging, did not reveal the same correlations. In conclusion, we found that WSS has the potential to be a viable and clinically useful noninvasive metric of PH disease progression and RV health. Future work should be focused on evaluating whether SAWSS has prognostic value in the management of PH and whether it can be used as a rapid reactivity assessment tool, which would aid in selection of appropriate therapies.

  19. Coenzyme Q10 prevents high glucose-induced oxidative stress in human umbilical vein endothelial cells.

    PubMed

    Tsuneki, Hiroshi; Sekizaki, Naoto; Suzuki, Takashi; Kobayashi, Shinjiro; Wada, Tsutomu; Okamoto, Tadashi; Kimura, Ikuko; Sasaoka, Toshiyasu

    2007-07-02

    Hyperglycemia-induced oxidative stress plays a crucial role in the pathogenesis of vascular complications in diabetes. Although some clinical evidences suggest the use of an antioxidant reagent coenzyme Q10 in diabetes with hypertension, the direct effect of coenzyme Q10 on the endothelial functions has not been examined. In the present study, we therefore investigated the protective effect of coenzyme Q10 against high glucose-induced oxidative stress in human umbilical vein endothelial cells (HUVEC). HUVEC exposed to high glucose (30 mM) exhibited abnormal properties, including the morphological and biochemical features of apoptosis, overproduction of reactive oxygen species, activation of protein kinase Cbeta2, and increase in endothelial nitric oxide synthase expression. Treatment with coenzyme Q10 strongly inhibited these changes in HUVEC under high glucose condition. In addition, coenzyme Q10 inhibited high glucose-induced cleavage of poly(ADP-ribose) polymerase, an endogenous caspase-3 substrate. These results suggest that coenzyme Q10 prevents reactive oxygen species-induced apoptosis through inhibition of the mitochondria-dependent caspase-3 pathway. Moreover, consistent with previous reports, high glucose caused upregulation of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) in HUVEC, and promoted the adhesion of U937 monocytic cells. Coenzyme Q10 displayed potent inhibitory effects against these endothelial abnormalities. Thus, we provide the first evidence that coenzyme Q10 has a beneficial effect in protecting against the endothelial dysfunction by high glucose-induced oxidative stress in vitro.

  20. Shear wave transducer for stress measurements in boreholes

    DOEpatents

    Mao, Nai-Hsien

    1987-01-01

    A technique and apparatus for estimating in situ stresses by measuring stress-induced velocity anisotropy around a borehole. Two sets each of radially and tangentially polarized transducers are placed inside the hole with displacement directions either parallel or perpendicular to the principal stress directions. With this configuration, relative travel times are measured by both a pulsed phase-locked loop technique and a cross correlation of digitized waveforms. The biaxial velocity data is used to back-calculate the applied stress.

  1. Inhibition of bacterial and leukocyte adhesion under shear stress conditions by material surface chemistry.

    PubMed

    Patel, Jasmine D; Ebert, Michael; Stokes, Ken; Ward, Robert; Anderson, James M

    2003-01-01

    Biomaterial-centered infections, initiated by bacterial adhesion, persist due to a compromised host immune response. Altering implant materials with surface modifying endgroups (SMEs) may enhance their biocompatibility by reducing bacterial and inflammatory cell adhesion. A rotating disc model, which generates shear stress within physiological ranges, was used to characterize adhesion of leukocytes and Staphylococcus epidermidis on polycarbonate-urethanes and polyetherurethanes modified with SMEs (polyethylene oxide, fluorocarbon and dimethylsiloxane) under dynamic flow conditions. Bacterial adhesion in the absence of serum was found to be mediated by shear stress and surface chemistry, with reduced adhesion exhibited on materials modified with polydimethylsiloxane and polyethylene oxide SMEs. In contrast, bacterial adhesion was enhanced on materials modified with fluorocarbon SMEs. In the presence of serum, bacterial adhesion was primarily neither material nor shear dependent. However, bacterial adhesion in serum was significantly reduced to < or = 10% compared to adhesion in serum-free media. Leukocyte adhesion in serum exhibited a shear dependency with increased adhesion occurring in regions exposed to lower shear-stress levels of < or = 7 dyne/cm2. Additionally, polydimethylsiloxane and polyethylene oxide SMEs reduced leukocyte adhesion on polyether-urethanes. In conclusion, these results suggest that surface chemistry and shear stress can mediate bacterial and cellular adhesion. Furthermore, materials modified with polyethylene oxide SMEs are capable of inhibiting bacterial adhesion, consequently minimizing the probability of biomaterial-centered infections.

  2. [Oxidative stress in endothelial cells and in diabetes type 2].

    PubMed

    Eckers, A; Altschmied, J; Haendeler, J

    2012-02-01

    Reactive oxygen species (ROS) are important signaling molecules in human cells. At physiological concentrations, they can for instance protect against apoptosis and act as secondary messengers in many different signaling pathways. Disturbance of redox homeostasis, i.e., the physiological balance between ROS generation and degradation, leads to not only increased ROS levels, so-called oxidative stress, but also results in damage to macromolecules and promotes the development of diseases and accelerates the aging process. The organism has various enzyme systems at hand to eliminate excess ROS. Their inactivation or degradation under conditions of oxidative stress is tightly linked to endothelial dysfunction due to endothelial cell apoptosis, a loss of telomerase activity, and telomere shortening. Restricted endothelial function causes cardiovascular diseases and diabetes type 2.

  3. Interaction of Vascular Smooth Muscle Cells Under Low Shear Stress

    NASA Technical Reports Server (NTRS)

    Seidel, Charles L.

    1998-01-01

    The blood vessel wall consists of three cellular layers, an outer adventitial, a middle medial and an inner intimal layer. When the blood vessel forms in the embryo it begins as a tube composed of a single cell type called endothelial cells. Over time, other cells are recruited from the surrounding tissue to form additional layers on the outer surface of the endothelial tube. The cells that are recruited are called mesenchymal cells. Mesenchymal cells are responsible for the production of connective tissue that holds the blood vessel together and for developing into vascular smooth muscle cells that are responsible for regulating the diameter of the vessel (1) and therefore, blood flow. In a fully developed blood vessel, the endothelial cells make- up the majority of cells in the intimal layer while the mesenchymal cells make-up the majority of cells in the medial and adventitial layers. Within the medial layer of a mature vessel, cells are organized into multiple circular layers of alternating bands of connective tissue and cells. The cell layer is composed of a mixture of mesenchymal cells that have not developed into smooth muscle cells and fully developed smooth muscle cells (2). The assembly and organization of complex tissues is directed in part by a signaling system composed of proteins on the cell surface called adhesion molecules. Adhesion molecules enable cells to recognize each other as well as the composition of the connective tissue in which they reside (3). It was hypothesized that the different cell types that compose the vascular wall possess different adhesion molecules that enable them to recognize each other and through this recognition system, form the complex layered organization of the vascular wall. In other words, the layered organization is an intrinsic property of the cells. If this hypothesis is correct then the different cells that make up the vessel wall, when mixed together, should organize themselves into a layered structure

  4. Postprandial endothelial function, inflammation, and oxidative stress in obese children and adolescents.

    PubMed

    Metzig, Andrea M; Schwarzenberg, Sarah J; Fox, Claudia K; Deering, Mary M; Nathan, Brandon M; Kelly, Aaron S

    2011-06-01

    Most studies in adults suggest that acute glucose consumption induces a transient impairment in endothelial function. We hypothesized that obese youth would demonstrate reduced endothelial function and increased inflammation and oxidative stress following acute glucose ingestion and that transient elevations in plasma glucose would correlate with endothelial dysfunction, inflammation, and oxidative stress. Thirty-four obese (BMI ≥ 95th percentile) children and adolescents (age 12.4 ± 2.6 years; BMI = 37.9 ± 6.7 kg/m2; 50% females) underwent measurement of endothelial function (reactive hyperemic index (RHI)), glucose, insulin, C-reactive protein (CRP), interleukin-6 (IL-6), circulating oxidized low-density lipoprotein (oxLDL), and myeloperoxidase (MPO) in a fasting state and at 1- and 2-h following glucose ingestion. Repeated measures ANOVA with Tukey post-tests and Pearson correlations were performed. Glucose and insulin levels significantly increased at 1- and 2-h (all P values < 0.001). Compared to baseline, there were no statistically significant differences in 1- and 2-h RHI, CRP, IL-6, and oxLDL. However, MPO significantly decreased at the 1- (P < 0.05) and 2-h (P < 0.001) time points. At the 1-h time point, glucose level was significantly inversely correlated with RHI (r = -0.40, P < 0.05) and at the 2-h time point, glucose level was positively correlated with MPO (r = 0.40, P < 0.05). An acute oral glucose load does not reduce endothelial function or increase levels of inflammation or oxidative stress in obese youth. However, associations of postprandial hyperglycemia with endothelial function and oxidative stress may have implications for individuals with impaired glucose tolerance or frank type 2 diabetes.

  5. Shear stress-induced mechanotransduction protein deregulation and vasculopathy in a mouse model of progeria

    PubMed Central

    2014-01-01

    Introduction A mouse model of progeria derived by insertion of the human mutant LMNA gene (mLMNA), producing mutant lamin A, shows loss of smooth muscle cells in the media of the ascending aorta. We hypothesized that high shear stress, in the presence of mutant lamin A, induces this vasculopathy and tried to define the molecular and cellular basis for aortic vasculopathy. Methods Ascending and descending aortas from wild type (WT) and mLMNA+ mice were compared using proteomics, Western blots, PCR and immunostaining. To determine whether high fluidic shear stress, known to occur in the ascending aorta, contributed to the vasculopathy, we exposed descending aortas of mLMNA+ mice, with no apparent vasculopathy, to 75 dynes/cm2 shear stress for 30 minutes using a microfluidic system. Results When the mice were one year of age, expression of several mechanotransduction proteins in the ascending aorta, including vimentin, decreased in mLMNA+ mice but no decrease occurred in the descending aorta. High fluidic shear stress produced a significant reduction in vimentin of mLMNA+ mice but not in similarly treated WT mice. Conclusions The occurrence of mutant lamin A and high shear stress correlate with a reduction in the level of mechanotransduction proteins in smooth muscle cells of the media. Reduction of these proteins may contribute over time to development of vasculopathy in the ascending aorta in progeria syndrome. PMID:24661531

  6. Large scale structures in a turbulent boundary layer and their imprint on wall shear stress

    NASA Astrophysics Data System (ADS)

    Pabon, Rommel; Barnard, Casey; Ukeiley, Lawrence; Sheplak, Mark

    2015-11-01

    Experiments were performed on a turbulent boundary layer developing on a flat plate model under zero pressure gradient flow. A MEMS differential capacitive shear stress sensor with a 1 mm × 1 mm floating element was used to capture the fluctuating wall shear stress simultaneously with streamwise velocity measurements from a hot-wire anemometer traversed in the wall normal direction. Near the wall, the peak in the cross correlation corresponds to an organized motion inclined 45° from the wall. In the outer region, the peak diminishes in value, but is still significant at a distance greater than half the boundary layer thickness, and corresponds to a structure inclined 14° from the wall. High coherence between the two signals was found for the low-frequency content, reinforcing the belief that large scale structures have a vital impact on wall shear stress. Thus, estimation of the wall shear stress from the low-frequency velocity signal will be performed, and is expected to be statistically significant in the outer boundary layer. Additionally, conditionally averaged mean velocity profiles will be presented to assess the effects of high and low shear stress. This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under Grant No. DGE-1315138.

  7. Black tea protects against hypertension-associated endothelial dysfunction through alleviation of endoplasmic reticulum stress

    PubMed Central

    San Cheang, Wai; Yuen Ngai, Ching; Yen Tam, Ye; Yu Tian, Xiao; Tak Wong, Wing; Zhang, Yang; Wai Lau, Chi; Chen, Zhen Yu; Bian, Zhao-Xiang; Huang, Yu; Ping Leung, Fung

    2015-01-01

    Hypertensive patients have been found to be associated with elevated levels of homocysteine, known as hyperhomocysteinemia. Homocysteine (Hcy) can induce endoplasmic reticulum (ER) stress in endothelial cells. This study aims to investigate whether black tea (BT) protects against hypertension-associated endothelial dysfunction through alleviation of ER stress. Rat aortae and cultured rat aortic endothelial cells were treated with Hcy, BT extract, and theaflavin-3,3’-digallate (TF3). Male Sprague Dawley rats were infused with angiotensin II (Ang II) to induce hypertension and orally administrated with BT extract at 15 mg/kg/day for 2 weeks. Hcy impaired endothelium-dependent relaxations of rat aortae and led to ER stress in endothelial cells, which were ameliorated by co-incubation of BT extract and TF3. The blood pressure of Ang II-infused rats and plasma Hcy level were normalized by BT consumption. Impaired endothelium-dependent relaxations in renal arteries, carotid arteries and aortae, and flow-mediated dilatations in third-order mesenteric resistance arteries were improved. Elevations of ER stress markers and ROS level, plus down-regulation of Hcy metabolic enzymes in aortae from Ang II-infused rats were prevented by BT treatment. Our data reveal the novel cardiovascular benefits of BT in ameliorating vascular dysfunctions, providing insight into developing BT into beneficial dietary supplements in hypertensive patients. PMID:25976123

  8. Rheological regional properties of brain tissue studied under cyclic creep/ recovery shear stresses

    NASA Astrophysics Data System (ADS)

    Boudjema, F.; Lounis, M.; Khelidj, B.; Bessai, N.

    2015-04-01

    The rheological properties of brain tissue were studied by repeated creep-recovery shear tests under static conditions for different regions. Corpus callosum CC, Thalamus Th and Corona radiata CR. Non-linear viscoelastic model was also proposed to characterize the transient/steady states of shear creep results. From the creep-recovery data it was obvious that the brain tissues show high regional anisotropy. However. the both samples exhibit fluid viscoelastic properties in the first shear stress cycle of 100 Pa, while this behaviour evolutes to solid viscoelastic with cyclic effect.

  9. Bed shear stress estimation on an open intertidal flat using in situ measurements

    NASA Astrophysics Data System (ADS)

    Zhu, Q.; van Prooijen, B. C.; Wang, Z. B.; Ma, Y. X.; Yang, S. L.

    2016-12-01

    Accurate estimations for the bed shear stress are essential to predict the erosion and deposition processes in estuaries and coasts. This study used high-frequency in situ measurements of water depths and near-bed velocities to estimate bed shear stress on an open intertidal flat in the Yangtze Delta, China. To determine the current-induced bed shear stress (τc) the in situ near-bed velocities were first decomposed from the turbulent velocity into separate wave orbital velocities using two approaches: a moving average (MA) and energy spectrum analysis (ESA). τc was then calculated and evaluated using the log-profile (LP), turbulent kinetic energy (TKE), modified TKE (TKEw), Reynolds stress (RS), and inertial dissipation (ID) methods. Wave-induced bed shear stress (τw) was estimated using classic linear wave theory. The total bed shear stress (τcw) was determined based on the Grant-Madsen wave-current interaction model (WCI). The results demonstrate that when the ratio of significant wave height to water depth (Hs/h) is greater than 0.25, τcw is significantly overestimated because the vertical velocity fluctuations are contaminated by the surface waves generated by high winds. In addition, wind enhances the total bed shear stress as a result of the increases in both τw and τc generated by the greater wave height and reinforcing of vertical turbulence, respectively. From a comparison of these various methods, the TKEw method associated with ESA decomposition was found to be the best approach because: (1) this method generates the highest mean index of agreement; (2) it uses vertical velocities that are less affected by Doppler noise; and (3) it is less sensitive to the near-bed stratification structure and uncertainty in bed location and roughness.

  10. Effects of fluid shear stress on polyelectrolyte multilayers by neutron scattering studies

    SciTech Connect

    Singh, Saurabh; Junghans, Ann; Watkins, Erik; Kapoor, Yash; Toomey, Ryan; Majewski, Jaroslaw

    2015-02-17

    The structure of layer-by-layer (LbL) deposited nanofilm coatings consists of alternating polyethylenimine (PEI) and polystyrenesulfonate (PSS) films deposited on a single crystal quartz substrate. LbL-deposited nanofilms were investigated by neutron reflectomery (NR) in contact with water in the static and fluid shear stress conditions. The fluid shear stress was applied through a laminar flow of the liquid parallel to the quartz/polymer interface in a custom-built solid–liquid interface cell. The scattering length density profiles obtained from NR results of these polyelectrolyte multilayers (PEM), measured under different shear conditions, showed proportional decrease of volume fraction of water hydrating the polymers. For the highest shear rate applied (ca. 6800 s–1) the water volume fraction decreased by approximately 7%. The decrease of the volume fraction of water was homogeneous through the thickness of the film. Since there were not any significant changes in the total polymer thickness, it resulted in negative osmotic pressures in the film. The PEM films were compared with the behavior of thin films of thermoresponsive poly(N-isopropylacrylamide) (pNIPAM) deposited via spin-coating. The PEM and pNIPAM differ in their interactions with water molecules, and they showed opposite behaviors under the fluid shear stress. In both cases the polymer hydration was reversible upon the restoration of static conditions. Furthermore, a theoretical explanation is given to explain this difference in the effect of shear on hydration of polymeric thin films.

  11. Lamin A/C deficiency reduces circulating tumor cell resistance to fluid shear stress

    PubMed Central

    Denais, Celine; Chan, Maxine F.; Wang, Zhexiao; Lammerding, Jan

    2015-01-01

    Metastasis contributes to over 90% of cancer-related deaths and is initiated when cancer cells detach from the primary tumor, invade the basement membrane, and enter the circulation as circulating tumor cells (CTCs). While metastasis is viewed as an inefficient process with most CTCs dying within the bloodstream, it is evident that some CTCs are capable of resisting hemodynamic shear forces to form secondary tumors in distant tissues. We hypothesized that nuclear lamins A and C (A/C) act as key structural components within CTCs necessary to resist destruction from elevated shear forces of the bloodstream. Herein, we show that, compared with nonmalignant epithelial cells, tumor cells are resistant to elevated fluid shear forces in vitro that mimic those within the bloodstream, as evidenced by significant decreases in cellular apoptosis and necrosis. Knockdown of lamin A/C significantly reduced tumor cell resistance to fluid shear stress, with significantly increased cell death compared with parental tumor cell and nontargeting controls. Interestingly, lamin A/C knockdown increased shear stress-induced tumor cell apoptosis, but did not significantly affect cellular necrosis. These data demonstrate that lamin A/C is an important structural component that enables tumor cell resistance to fluid shear stress-mediated death in the bloodstream, and may thus facilitate survival and hematogenous metastasis of CTCs. PMID:26447202

  12. Tumor cell cycle arrest induced by shear stress: Roles of integrins and Smad

    PubMed Central

    Chang, Shun-Fu; Chang, Cheng Allen; Lee, Ding-Yu; Lee, Pei-Ling; Yeh, Yu-Ming; Yeh, Chiuan-Ren; Cheng, Cheng-Kung; Chien, Shu; Chiu, Jeng-Jiann

    2008-01-01

    Interstitial flow in and around tumor tissue affects the mechanical microenvironment to modulate tumor cell growth and metastasis. We investigated the roles of flow-induced shear stress in modulating cell cycle distribution in four tumor cell lines and the underlying mechanisms. In all four cell lines, incubation under static conditions for 24 or 48 h led to G0/G1 arrest; in contrast, shear stress (12 dynes/cm2) induced G2/M arrest. The molecular basis of the shear effect was analyzed, and the presentation on molecular mechanism is focused on human MG63 osteosarcoma cells. Shear stress induced increased expressions of cyclin B1 and p21CIP1 and decreased expressions of cyclins A, D1, and E, cyclin-dependent protein kinases (Cdk)-1, -2, -4, and -6, and p27KIP1 as well as a decrease in Cdk1 activity. Using specific antibodies and small interfering RNA, we found that the shear-induced G2/M arrest and corresponding changes in G2/M regulatory protein expression and activity were mediated by αvβ3 and β1 integrins through bone morphogenetic protein receptor type IA-specific Smad1 and Smad5. Shear stress also down-regulated runt-related transcription factor 2 (Runx2) binding activity and osteocalcin and alkaline phosphatase expressions in MG63 cells; these responses were mediated by αvβ3 and β1 integrins through Smad5. Our findings provide insights into the mechanism by which shear stress induces G2/M arrest in tumor cells and inhibits cell differentiation and demonstrate the importance of mechanical microenvironment in modulating molecular signaling, gene expression, cell cycle, and functions in tumor cells. PMID:18310319

  13. Injectable shear-thinning hydrogels to deliver endothelial progenitor cells, enhance cell engraftment, and improve ischemic myocardium

    PubMed Central

    Gaffey, Ann C.; Chen, Minna H.; Venkataraman, Chantel M.; Trubelja, Alen; Rodell, Christopher B.; Dinh, Patrick V.; Hung, George; MacArthur, John W.; Soopan, Renganaden V.; Burdick, Jason A.; Atluri, Pavan

    2015-01-01

    OBJECTIVES The clinical translation of cell based therapies for ischemic heart disease has been limited due to low cell retention (<1%) within and poor targeting to ischemic myocardium. To address these issues, we developed an injectable shear-thinning hyaluronic acid hydrogel (STG) and endothelial progenitor cell construct (STG-EPC). The STG assembles due to interactions of adamantine and β-cyclodextrin modified hyaluronic acid. It is shear-thinning to permit delivery via a syringe, and self-heals upon injection within the ischemic myocardium. This directed therapy to the ischemic myocardial borderzone enables direct cell delivery to address adverse remodeling after myocardial infarction. We hypothesize that this system will enhance vasculogenesis to improve myocardial stabilization in the context of a clinically translatable therapy. METHODS EPCs (DiLDL+ VEGFR2+ CD34+) were harvested from adult male Wistar Rats, cultured, and then suspended in the STG. In vitro viability was quantified using a live-dead stain of EPCs. STG-EPC constructs were injected at the borderzone of ischemic rat myocardium after acute myocardial infarction (left anterior descending coronary artery ligation). The migration of the eGFP+ EPCs from the construct to ischemic myocardium was analyzed using fluorescent microscopy. Vasculogenesis, myocardial remodeling, and hemodynamic function were analyzed in 4 groups: control (PBS injection), intramyocardial injection of EPCs alone (EPC), injection of the STG alone (STG), and treatment with the gel-EPC construct (STG-EPC). Hemodynamics and ventricular geometry were quantified using echocardiography and Doppler flow analysis. RESULTS EPCs demonstrated viability within the STG. A marked increase in EPC engraftment was observed one-week post-injection within the treated myocardium with gel delivery when compared to EPC injection alone (17.2 ± 0.8 cells/HPF vs. 3.5 cells ± 1.3 cells/HPF, p = 0.0002). A statistically significant increase in

  14. Crack initiation observation and local stress analysis in shear fracture tests of ultra-high strength steels

    NASA Astrophysics Data System (ADS)

    Ma, Ninshu; Takada, Kenji; Sugimoto, Nao

    2016-08-01

    To investigate the local strain and stress at the crack initiation position in shear fracture test pieces of ultra-high strength steels, a butterfly shear fracture specimen was employed. The crack initiation position and propagation direction were observed during shear fracture tests by high speed cameras and investigated through analysing the fracture surface by scanning electron microscope. Further, the finite element method was employed and the stress-triaxiality at the crack initiation position was investigated. It can be obtained that the crack initiated at the position where the stress state is close to uniaxial tensile state or plane strain state more than pure shear stress state.

  15. Modeling the curvature and interface shear stress of GaN-sapphire system

    NASA Astrophysics Data System (ADS)

    Li, Jia; Shi, Junjie; Wu, Jiejun; Liu, Huizhao

    2016-03-01

    The curvature and interface shear stress of GaN-sapphire system are studied by establishing the mechanical equations based on two main assumptions: (a) the thickness of GaN film can be compared to the thickness of sapphire substrate, and (b) the thickness of GaN film is non-uniform. Our results show that the curvature of GaN-sapphire system is a variable within the whole circular system. The interface shear stress changes direction around at the middle of radius for the circular system, and the curvature have an important effect on the interface shear stress due to the consideration of non-uniform thickness for GaN film.

  16. An integrated temperature-compensated flexible shear-stress sensor microarray with concentrated leading-wire.

    PubMed

    Tang, Jian; Liu, Wu; Zhang, Weiping; Sun, Yongming; Chen, Honghai

    2016-02-01

    Flexible shear stress sensor is quite important for characterizing curved surface flows. In this work, a novel integrated shear stress sensor microarray is designed with twenty parallel channels, which share the concentrated leading-wire to transmit the ground signal. Electrical pads in rows are easily connected to the circuits with two separate Wheatstone bridges and constant-temperature-difference mode operation is provided for the hot-wires. Temperature crosstalk between adjacent hot-wires is prevented well and the effectiveness of the temperature compensated circuits is verified. Relatively large output response is obtained as the shear stress varies and the sensitivity of the sensors is measured about 0.086 V(2)/Pa(1/3) with nonlinearity lower than 1%, revealing high performance characteristic of the sensors.

  17. The Effects of Hemodynamic Shear Stress on Stemness of Acute Myelogenous Leukemia (AML)

    NASA Astrophysics Data System (ADS)

    Raddatz, Andrew; Triantafillu, Ursula; Kim, Yonghyun (John)

    2015-11-01

    Cancer stem cells (CSCs) have recently been identified as the root cause of tumors generated from cancer cell populations. This is because these CSCs are drug-resistant and have the ability to self-renew and differentiate. Current methods of culturing CSCs require much time and money, so cancer cell culture protocols, which maximize yield of CSCs are needed. It was hypothesized that the quantity of Acute myelogenous leukemia stem cells (LSCs) would increase after applying shear stress to the leukemia cells based on previous studies with breast cancer in bioreactors. The shear stress was applied by pumping the cells through narrow tubing to mimic the in vivo bloodstream environment. In support of the hypothesis, shear stress was found to increase the amount of LSCs in a given leukemia population. This work was supported by NSF REU Site Award 1358991.

  18. Alteration of mean wall shear stress near an oscillating stagnation point.

    PubMed

    Hazel, A L; Pedley, T J

    1998-04-01

    The site opposite an end-to-side anastomosis, resulting from femoral bypass surgery, and the carotid sinus are two regions well known to be prone to fibrous intimal hyperplasia or atherogenesis, respectively. The blood flow at these two sites features a stagnation point, which oscillates in strength and position. Mathematical models are used to determine some of the features of such a flow; in particular, the mean wall shear stress is calculated. The positional oscillations cause a significant change in the distribution and magnitude of the mean wall shear stress from that of the well-studied case of a stagnation point that oscillates only in strength. It is therefore proposed that the recorded effect of time dependence in the flow upon atherogenesis could still be a result of the distribution of the mean and not the time-varying components of the wall shear stress.

  19. The Effects of Static Coulomb, Normal and Shear Stress Changes on Earthquake Occurrence in Southern California

    NASA Astrophysics Data System (ADS)

    Strader, A. E.; Jackson, D. D.

    2011-12-01

    Deng & Sykes (1997) found a strong correlation between receiver earthquake location and positive increase in Coulomb stress (ΔCFF). Assuming a coefficient of friction of 0.6, and resolving stresses onto assumed fault planes with uniform orientation parallel to average Pacific-North American plate motion, they found that only 15% of receiver earthquakes occur in "stress shadows" where the Coulomb stress change should impede faulting. We extended their study by adding two source earthquakes (Hector Mine, 1999 and El Mayor-Cucupah, 2010), and calculating the stress changes at the locations of 134 receiver earthquakes with magnitude 4.4 and greater after 1999. We examined shear stress, normal stress, and Coulomb stress, resolving stresses onto four different hypothetical fault planes: smoothed seismicity-based planes, a weighted average of nearby fault-plane orientations, and the two nodal planes of weighed average moment tensors of nearby earthquakes. We also computed shear, normal, and Coulomb stress histories oriented according to the four choices of fault orientation, and tested the effect of total stress change on receiver earthquake magnitude. Our chi square test results indicate that, with 95% confidence, receiver earthquakes do not tend to avoid stress shadows, and that the choice of plane onto which stress is resolved does not affect the result. On average, 39% of earthquakes occur at the time of maximum stress at the event location, with no significant variation depending on the choice of rupture plane or type of stress change. We found no correlation between earthquake magnitude and total stress change at the events' locations. These results suggest that instantaneous cumulative Coulomb stress, as we and Deng & Sykes modeled it, does not strongly control the locations of future earthquakes. The lack of correlation between Coulomb stress change and magnitude suggests that modeled Coulomb stress change does not control the size of earthquakes once they

  20. Shear stress transmission model for the flagellar rotary motor.

    PubMed

    Mitsui, Toshio; Ohshima, Hiroyuki

    2008-09-01

    Most bacteria that swim are propelled by flagellar filaments, which are driven by a rotary motor powered by proton flux. The mechanism of the flagellar motor is discussed by reforming the model proposed by the present authors in 2005. It is shown that the mean strength of Coulomb field produced by a proton passing the channel is very strong in the Mot assembly so that the Mot assembly can be a shear force generator and induce the flagellar rotation. The model gives clear calculation results in agreement with experimental observations, e g., for the characteristic torque-velocity relationship of the flagellar rotation.

  1. Theory and Practice of Shear/Stress Strain Gage Hygrometry

    NASA Technical Reports Server (NTRS)

    Shams, Qamar A.; Fenner, Ralph L.

    2006-01-01

    Mechanical hygrometry has progressed during the last several decades from crude hygroscopes to state-of-the art strain-gage sensors. The strain-gage devices vary from different metallic beams to strain-gage sensors using cellulose crystallite elements, held in full shear restraint. This old technique is still in use but several companies are now actively pursuing development of MEMS miniaturized humidity sensors. These new sensors use polyimide thin film for water vapor adsorption and desorption. This paper will provide overview about modern humidity sensors.

  2. Shear-stress fluctuations in self-assembled transient elastic networks

    NASA Astrophysics Data System (ADS)

    Wittmer, J. P.; Kriuchevskyi, I.; Cavallo, A.; Xu, H.; Baschnagel, J.

    2016-06-01

    Focusing on shear-stress fluctuations, we investigate numerically a simple generic model for self-assembled transient networks formed by repulsive beads reversibly bridged by ideal springs. With Δ t being the sampling time and t(f ) ˜1 /f the Maxwell relaxation time (set by the spring recombination frequency f ), the dimensionless parameter Δ x =Δ t /t(f ) is systematically scanned from the liquid limit (Δ x ≫1 ) to the solid limit (Δ x ≪1 ) where the network topology is quenched and an ensemble average over m -independent configurations is required. Generalizing previous work on permanent networks, it is shown that the shear-stress relaxation modulus G (t ) may be efficiently determined for all Δ x using the simple-average expression G (t ) =μA-h (t ) with μA=G (0 ) characterizing the canonical-affine shear transformation of the system at t =0 and h (t ) the (rescaled) mean-square displacement of the instantaneous shear stress as a function of time t . This relation is compared to the standard expression G (t ) =c ˜(t ) using the (rescaled) shear-stress autocorrelation function c ˜(t ) . Lower bounds for the m configurations required by both relations are given.

  3. Interface shear stresses during ambulation with a below-knee prosthetic limb

    PubMed Central

    Sanders, Joan E.; Daly, Colin H.; Burgess, Ernest M.

    2015-01-01

    Shear stresses on a residual limb in a prosthetic socket are considered clinically to contribute to tissue breakdown in below-knee amputees. When applied simultaneously with normal stresses, they can cause injury within the skin or can generate an abrasion on the surface. To gain insight into shear stresses and parameters that affect them, interface stresses were recorded on below-knee amputee subjects during walking trials. On the tibial flares, resultant shear ranged from 5.6 kPa to 39.0 kPa, while on the posterior surface it ranged from 5.0 kPa to 40.7 kPa. During stance phase, anterior resultant shears on a socket were directed toward the apex while posterior resultant shears were directed downward approximately perpendicular to the ground. Waveform shapes were usually double-peaked, with the first peak at 25% to 40% into stance phase and the second peak at 65% to 85% into stance. Application of these results to residual limb tissue mechanics and prosthetic design is discussed. PMID:1432723

  4. Estimation of wall shear stress in bypass grafts with computational fluid dynamics method.

    PubMed

    Goubergrits, L; Affeld, K; Wellnhofer, E; ZurbrüggR; Holmer, T

    2001-03-01

    Coronary artery bypass graft (CABG) operation for coronary artery disease with different types of grafts has a large clinical application world wide. Immediately after this operation patients are usually relieved of their chest pain and have improved cardiac function. However, after a while, these bypass grafts may fail due to for example, neointimal hyperplasia or thrombosis. One of the causes for this bypass graft failure is assumed to be the blood flow with low wall shear stress. The aim of this research is to estimate the wall shear stress in a graft and thus to locate areas were wall shear stress is low. This was done with the help of a blood flow computer model. Post-operative biplane angiograms of the graft were recorded, and from these the three-dimensional geometry of the graft was reconstructed and imported into the computational fluid dynamics (CFD) program FLUENT. The stationary diastolic flow through the grafts was calculated, and the wall shear stress distribution was estimated. This procedure was carried out for one native vessel and two different types of bypass grafts. One bypass graft was a saphenous vein and the other one was a varicose saphenous vein encased in a fine, flexible metal mesh. The mesh was attached to give the graft a defined diameter. The computational results show that each graft has distinct areas of low wall shear stress. The graft with the metal mesh has an area of low wall shear stress (< 1 Pa, stationary flow), which is four times smaller than the respective areas in the other graft and in the native vessel. This is thought to be caused by the smaller and more uniform diameter of the metal mesh-reinforced graft.

  5. Critical shear stress for erosion of cohesive soils subjected to temperatures typical of wildfires

    USGS Publications Warehouse

    Moody, J.A.; Dungan, Smith J.; Ragan, B.W.

    2005-01-01

    [1] Increased erosion is a well-known response after wildfire. To predict and to model erosion on a landscape scale requires knowledge of the critical shear stress for the initiation of motion of soil particles. As this soil property is temperature-dependent, a quantitative relation between critical shear stress and the temperatures to which the soils have been subjected during a wildfire is required. In this study the critical shear stress was measured in a recirculating flume using samples of forest soil exposed to different temperatures (40??-550??C) for 1 hour. Results were obtained for four replicates of soils derived from three different types of parent material (granitic bedrock, sandstone, and volcanic tuffs). In general, the relation between critical shear stress and temperature can be separated into three different temperature ranges (275??C), which are similar to those for water repellency and temperature. The critical shear stress was most variable (1.0-2.0 N m-2) for temperatures 2.0 N m-2) between 175?? and 275??C, and was essentially constant (0.5-0.8 N m-2) for temperatures >275??C. The changes in critical shear stress with temperature were found to be essentially independent of soil type and suggest that erosion processes in burned watersheds can be modeled more simply than erosion processes in unburned watersheds. Wildfire reduces the spatial variability of soil erodibility associated with unburned watersheds by eliminating the complex effects of vegetation in protecting soils and by reducing the range of cohesion associated with different types of unburned soils. Our results indicate that modeling the erosional response after a wildfire depends primarily on determining the spatial distribution of the maximum soil temperatures that were reached during the wildfire. Copyright 2005 by the American Geophysical Union.

  6. Role of endothelial nitric oxide synthase (eNOS) in chronic stress-promoted tumour growth

    PubMed Central

    Barbieri, Antonio; Palma, Giuseppe; Rosati, Alessandra; Giudice, Aldo; Falco, Antonia; Petrillo, Antonella; Petrillo, Mario; Bimonte, Sabrina; Benedetto, Maria Di; Esposito, Giuseppe; Stiuso, Paola; Abbruzzese, Alberto; Caraglia, Michele; Arra, Claudio

    2012-01-01

    Abstract Accumulating evidence suggests that chronic stress can be a cofactor for the initiation and progression of cancer. Here we evaluated the role of endothelial nitric oxide synthase (eNOS) in stress-promoted tumour growth of murine B16F10 melanoma cell line in C57BL/6 mice. Animals subjected to restraint stress showed increased levels adrenocorticotropic hormone, enlarged adrenal glands, reduced thymus weight and a 3.61-fold increase in tumour growth in respect to no-stressed animals. Tumour growth was significantly reduced in mice treated with the β-antagonist propranolol. Tumour samples obtained from stressed mice displayed high levels of vascular endothelial growth factor (VEGF) protein in immunohistochemistry. Because VEGF can induce eNOS increase, and nitric oxide is a relevant factor in angiogenesis, we assessed the levels of eNOS protein by Western blot analysis. We found a significant increase in eNOS levels in tumour samples from stressed mice, indicating an involvement of this enzyme in stress-induced tumour growth. Accordingly, chronic stress did not promote tumour growth in eNOS−/− mice. These results disclose for the first time a pivotal role for eNOS in chronic stress-induced initiation and promotion of tumour growth. PMID:21722303

  7. Distribution of shear stress over smooth muscle cells in deformable arterial wall.

    PubMed

    Dabagh, Mahsa; Jalali, Payman; Konttinen, Yrjö T; Sarkomaa, Pertti

    2008-07-01

    A biphasic, anisotropic model of the deformable aortic wall in combination with computational fluid dynamics is used to investigate the variation of shear stress over smooth muscle cells (SMCs) with transmural pressure. The media layer is modeled as a porous medium consisting of SMCs and a homogeneous porous medium of interstitial fluid and elastin, collagen and proteoglycans fibers. Interstitial fluid enters the media through fenestral pores, which are distributed over the internal elastic lamina (IEL). The IEL is considered as an impermeable barrier to fluid flow except at fenestral pores. The thickness and the radius of aortic wall vary with transmural pressure ranging from 10 to 180 mm Hg. It is assumed that SMCs are cylinders with a circular cross section at 0 mm Hg. As the transmural pressure increases, SMCs elongate with simultaneous change of cross sectional shape into ellipse according to the strain field in the media. Results demonstrate that the variation of shear stress within the media layer is significantly dependent on the configuration and cross sectional shape of SMCs. In the staggered array of SMCs, the shear stress over the first SMC nearest to the IEL is about 2.2 times lower than that of the square array. The shear stress even over the second nearest SMC to the IEL is considerably higher (about 15%) in the staggered array. In addition to configuration and cross sectional shape of SMCs, the variation of structural properties of the media layer with pressure and the sensitivity of the local shear stress to the minimum distance between SMCs and the IEL (reducing with transmural pressure) between SMCs and the IEL are studied. At 180 mm Hg, the ratio of the local shear stress of the nearest SMC to that of the second nearest SMC is 4.8 in the square array, whereas it reduces to about 1.8 in the staggered array. The importance of the fluid shear stress is associated with its role in the biomolecular state of smooth muscle cells bearing the shear

  8. The significance of electrically induced shear stress in drainage of thin aqueous films

    NASA Astrophysics Data System (ADS)

    Ajaev, Vladimir; Ketelaar, Christiaan

    2014-11-01

    We develop a model of drainage of a microscale thin aqueous film separating a gas bubble and a solid wall. In contrast to previous studies, the electrostatic effects are accounted for not only in the normal but also in the shear stress balance at the liquid-gas interface. We show that the action of the tangential component of the electric field leads to potentially strong spatially variable shear stress at the deforming charged interface. This previously overlooked effect turns out to be essential for correctly estimating the long-time drainage rates. Time-dependent fluid interface shapes predicted by our model are in very good agreement with the experimental data.

  9. Significance of electrically induced shear stress in drainage of thin aqueous films

    NASA Astrophysics Data System (ADS)

    Ketelaar, Christiaan; Ajaev, Vladimir S.

    2015-05-01

    We develop a novel model of drainage of microscale thin aqueous film separating a gas bubble and a solid wall. In contrast to previous studies, the electrostatic effects are accounted for not only in the normal but also in the shear stress balance at the liquid-gas interface. We show that the action of the tangential component of the electric field leads to potentially strong spatially variable shear stress at the deforming charged interface. This previously overlooked effect turns out to be essential for correctly estimating the long-time drainage rates. Comparison of time-dependent fluid interface shapes predicted by our model with the experimental data is discussed.

  10. Beta Blockers Suppress Dextrose-Induced Endoplasmic Reticulum Stress, Oxidative Stress, and Apoptosis in Human Coronary Artery Endothelial Cells.

    PubMed

    Haas, Michael J; Kurban, William; Shah, Harshit; Onstead-Haas, Luisa; Mooradian, Arshag D

    Beta blockers are known to have favorable effects on endothelial function partly because of their capacity to reduce oxidative stress. To determine whether beta blockers can also prevent dextrose-induced endoplasmic reticulum (ER) stress in addition to their antioxidative effects, human coronary artery endothelial cells and hepatocyte-derived HepG2 cells were treated with 27.5 mM dextrose for 24 hours in the presence of carvedilol (a lipophilic beta blockers with alpha blocking activity), propranolol (a lipophilic nonselective beta blockers), and atenolol (a water-soluble selective beta blockers), and ER stress, oxidative, stress and cell death were measured. ER stress was measured using the placental alkaline phosphatase assay and Western blot analysis of glucose regulated protein 78, c-Jun-N-terminal kinase (JNK), phospho-JNK, eukaryotic initiating factor 2α (eIF2α), and phospho-eIF2α and measurement of X-box binding protein 1 (XBP1) mRNA splicing using reverse transcriptase-polymerase chain reaction. Superoxide (SO) generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride (MCLA) chemiluminescence. Cell viability was measured by propidium iodide staining method. The ER stress, SO production, and cell death induced by 27.5 mM dextrose were inhibited by all 3 beta blockers tested. The antioxidative and ER stress reducing effects of beta blockers were also observed in HepG2 cells. The salutary effects of beta blockers on endothelial cells in reducing both ER stress and oxidative stress may contribute to the cardioprotective effects of these agents.

  11. Surface Shear Stress Around a Single Flexible Live Plant and a Rigid Cylinder

    NASA Astrophysics Data System (ADS)

    Walter, B. A.; Gromke, C.; Leonard, K. C.; Clifton, A.; Lehning, M.

    2010-12-01

    The sheltering effect of vegetation against soil erosion and snow transport has direct implications on land degradation and local water storage as snow in many arid and semi arid regions. Plants influence the erosion, transport and redeposition of soil and snow by the wind through momentum absorption, local stress concentration, trapping particles in motion and reducing the area of sediment exposed to the wind. The shear stress distributions on the ground beneath plant canopies determine the onset and magnitude of differential soil and snow erosion on rough or vegetated surfaces, but this has been studied exclusively with artificial and rigid vegetation elements thus far. Real plants have highly irregular structures that can be extremely flexible and porous. They align with the flow at higher wind speeds, resulting in considerable changes to the drag and flow regimes relative to rigid imitations of comparable size. We present measurements in the SLF atmospheric boundary layer wind tunnel of the surface shear stress distribution around a live grass plant (Lolium Perenne) and a solid cylinder of comparable size. Irwin sensors are used to measure pressure differences close to the surface which can be calibrated with surface shear stress velocities. The basal to frontal area index of the plant and the cylinder as well as the Reynolds number of the two experimental setups have been checked for similarity and show good agreement. Distinctive differences between the shear stress pattern around the plant and the cylinder can be attributed to the influence of the plant’s porosity and flexibility. The sheltered zone behind the plant is narrower in cross-stream and longer in streamwise direction than that of the cylinder. For the plant, the lowest shear stresses in the sheltered zone are 50% lower than the mean surface shear stress (τ = 0.15 N/m2) in the undisturbed flow. The sheltering was higher behind the cylinder with values reduced by 70% relative to background.

  12. Mechanism and kinetics of biofilm growth process influenced by shear stress in sewers.

    PubMed

    Ai, Hainan; Xu, Jingwei; Huang, Wei; He, Qiang; Ni, Bingjie; Wang, Yinliang

    2016-01-01

    Sewer biofilms play an important role in the biotransformation of substances for methane and sulfide emission in sewer networks. The dynamic flows and the particular shear stress in sewers are the key factors determining the growth of the sewer biofilm. In this work, the development of sewer biofilm with varying shear stress is specifically investigated to gain a comprehensive understanding of the sewer biofilm dynamics. Sewer biofilms were cultivated in laboratory-scale gravity sewers under different hydraulic conditions with the corresponding shell stresses are 1.12 Pa, 1.29 Pa and 1.45 Pa, respectively. The evolution of the biofilm thickness were monitored using microelectrodes, and the variation in total solids (TS) and extracellular polymer substance (EPS) levels in the biofilm were also measured. The results showed that the steady-state biofilm thickness were highly related to the corresponding shear stresses with the biofilm thickness of 2.4 ± 0.1 mm, 2.7 ± 0.1 mm and 2.2 ± 0.1 mm at shear stresses of 1.12 Pa, 1.29 Pa and 1.45 Pa, respectively, which the chemical oxygen demand concentration is 400 mg/L approximately. Based on these observations, a kinetic model for describing the development of sewer biofilms was developed and demonstrated to be capable of reproducing all the experimental data.

  13. Seasonal Variation in Basal Shear Stress Beneath the Greenland Ice Sheet

    NASA Astrophysics Data System (ADS)

    Joughin, I.; Alley, R. B.; Behn, M. D.; Das, S. B.; Flowers, G. E.

    2015-12-01

    Over the last decade, it has been well established that in the ablation zone of the Greenland Ice Sheet, surface melt water makes its way to the bed and seasonally modulates ice-flow speed. With a conventional sliding law, the basal shear stress is proportional to the nonlinear product of the sliding speed and the effective pressure (difference between ice overburden and water pressure). Thus, when seasonal surface melting raises subglacial water pressure, it lowers the effective pressure, requiring additional sliding to restore the basal shear stress to maintain an overall force balance. This variation need not be uniform, however, and the basal hydrological system may produce variability at different spatial scales. To examine variability at scales of a few ice thicknesses, we use control-method inverse techniques to determine the basal shear stress using a shallow-shelf, ice-flow model constrained by speckle-tracked velocities measured over 11 and 22-day intervals. We begin by determining a reference basal shear stress estimated for a typical winter velocity field (typically over a 30-by-50 km region). We then determine the corresponding estimates for the region during periods of enhanced summer flow. In general, we find that relative to the winter data, summer basal shear stress tends to increase in areas of steep surface slope (high driving stress) and decrease, despite elevated speeds, in low slope regions, which often correspond to the basins where supraglacial lakes form. Computing the ratio of summer to winter effective pressure indicates little seasonal change in effective pressure for areas of high basal shear stress and a summer decrease in low-slope regions. This pattern is consistent with surface and bed slopes that drive water away from areas of high slopes and stress concentration (e.g., where ice flows over bedrock bumps) toward weak, low-slope regions of the bed. The net result is that, during the summer delivery of water to the bed, basal shear

  14. The microchannel flow model under shear stress and higher frequencies

    NASA Astrophysics Data System (ADS)

    Parker, K. J.

    2017-04-01

    The microchannel flow model provides a framework for considering the effect of the vascular bed on the time domain and frequency domain response of soft tissues. The derivation originates with a single small fluid-filled vessel in an elastic medium under uniaxial compression. A fractal branching vasculature is also assumed to be present in the tissue under consideration. This note considers two closely related issues. First, the response of the element under compression or shear as a function of the orientation of the fluid-filled vessel is considered. Second, the transition from quasistatic (Poiseuille’s Law) to dynamic (Womersley equations) fluid flow is examined to better predict the evolution of behavior at higher frequencies. These considerations expand the conceptual framework of the microchannel flow model, particularly the range and limits of validity.

  15. The microchannel flow model under shear stress and higher frequencies.

    PubMed

    Parker, Kevin J

    2017-02-24

    The microchannel flow model provides a framework for considering the effect of the vascular bed on the time domain and frequency domain response of soft tissues. The derivation originates with a single small fluid filled vessel in an elastic medium under uniaxial compression. A fractal branching vasculature is also assumed to be present in the tissue under consideration. This short technical note considers two closely related issues. First, the response of the element under compression or shear as a function of the orientation of the fluid-filled vessel is considered. Second, the transition from quasistatic (Poiseuille's Law) to dynamic (Womersley equations) fluid flow is examined to better predict the evolution of behavior at higher frequencies. These considerations expand the conceptual framework of the microchannel flow model, particularly the range and limits of validity.

  16. Design optimization of scaffold microstructures using wall shear stress criterion towards regulated flow-induced erosion.

    PubMed

    Chen, Yuhang; Schellekens, Michiel; Zhou, Shiwei; Cadman, Joseph; Li, Wei; Appleyard, Richard; Li, Qing

    2011-08-01

    Tissue scaffolds aim to provide a cell-friendly biomechanical environment for facilitating cell growth. Existing studies have shown significant demands for generating a certain level of wall shear stress (WSS) on scaffold microstructural surfaces for promoting cellular response and attachment efficacy. Recently, its role in shear-induced erosion of polymer scaffold has also drawn increasing attention. This paper proposes a bi-directional evolutionary structural optimization (BESO) approach for design of scaffold microstructure in terms of the WSS uniformity criterion, by downgrading highly-stressed solid elements into fluidic elements and/or upgrading lowly-stressed fluidic elements into solid elements. In addition to this, a computational model is presented to simulate shear-induced erosion process. The effective stiffness and permeability of initial and optimized scaffold microstructures are characterized by the finite element based homogenization technique to quantify the variations of mechanical properties of scaffold during erosion. The illustrative examples show that a uniform WSS is achieved within the optimized scaffold microstructures, and their architectural and biomechanical features are maintained for a longer lifetime during shear-induced erosion process. This study provides a mathematical means to the design optimization of cellular biomaterials in terms of the WSS criterion towards controllable shear-induced erosion.

  17. Non-Newtonian stress tensor and thermal conductivity tensor in granular plane shear flow

    NASA Astrophysics Data System (ADS)

    Alam, Meheboob; Saha, Saikat

    2014-11-01

    The non-Newtonian stress tensor and the heat flux in the plane shear flow of smooth inelastic disks are analysed from the Grad-level moment equations using the anisotropic Gaussian as a reference. Closed-form expressions for shear viscosity, pressure, first normal stress difference (N1) and the dissipation rate are given as functions of (i) the density or the area fraction (ν), (ii) the restitution coefficient (e), (iii) the dimensionless shear rate (R), (iv) the temperature anisotropy [ η, the difference between the principal eigenvalues of the second moment tensor] and (v) the angle (ϕ) between the principal directions of the shear tensor and the second moment tensor. Particle simulation data for a sheared hard-disk system is compared with theoretical results, with good agreement for p, μ and N1 over a large range of density. In contrast, the predictions from a Navier-Stokes order constitutive model are found to deviate significantly from both the simulation and the moment theory even at moderate values of e. We show that the gradient of the deviatoric part of the kinetic stress drives a heat current and the thermal conductivity is characterized by an anisotropic 2nd rank tensor for which explicit expressions are derived.

  18. The effect of bilayer composition on calcium ion transport facilitated by fluid shear stress.

    PubMed

    Giorgio, T D; Yek, S H

    1995-10-04

    Passive calcium ion permeability across liposome bilayers is increased during exposure to fluid shear forces attainable in the mammalian vasculature. In this study, liposomes prepared from three different lipid mixtures (phosphatidylcholine alone; phosphatidylcholine and cholesterol; a mixture of anionic and cationic phospholipids plus cholesterol) are exposed to uniform shear stress in a rotational viscometer. Liposome permeability to calcium ion is estimated from continuous measurement of free intraliposome calcium ion concentration using a fluorescence technique. Calcium ion permeability in the absence of fluid force and susceptibility to shear-induced permeability modulation are positively correlated with estimated bilayer compressibility. Fluid shear forces are presumed to influence bilayer packing and modulate defect formation in proportion to bilayer compressibility. Bilayer defects produced by fluid forces may increase liposome permeability.

  19. Hemodynamic wall shear stress profiles influence the magnitude and pattern of stenosis in a pig AV fistula.

    PubMed

    Krishnamoorthy, Mahesh K; Banerjee, Rupak K; Wang, Yang; Zhang, Jianhua; Roy, Abhijit Sinha; Khoury, Saeb F; Arend, Lois J; Rudich, Steve; Roy-Chaudhury, Prabir

    2008-12-01

    Venous stenosis is a significant problem in arteriovenous fistulae, likely due to anatomical configuration and wall shear stress profiles. To identify linkages between wall shear stress and the magnitude and pattern of vascular stenosis, we produced curved and straight fistulae in a pig model. A complete wall stress profile was calculated for the curved configuration and correlated with luminal stenosis. Computer modeling techniques were then used to derive a wall shear stress profile for the straight arteriovenous fistula. Differences in the wall shear stress profile of the curved and straight fistula were then related to histological findings. There was a marked inverse correlation between the magnitude of wall shear stress within different regions of the curved arteriovenous fistula and luminal stenosis in these same regions. There were also significantly greater differences in wall shear stress between the outer and inner walls of the straight as compared to curved arteriovenous fistula, which translated into a more eccentric histological pattern of intima-media thickening. Our results suggest a clear linkage between anatomical configuration, wall shear stress profiles, and the pattern of luminal stenosis and intima-media thickening in a pig model of arteriovenous fistula stenosis. These results suggest that fistula failure could be reduced by using computer modeling prior to surgical placement to alter the anatomical and, consequently, the wall shear stress profiles in an arteriovenous fistula.

  20. Methamphetamine disrupts blood-brain barrier function by induction of oxidative stress in brain endothelial cells.

    PubMed

    Ramirez, Servio H; Potula, Raghava; Fan, Shongshan; Eidem, Tess; Papugani, Anil; Reichenbach, Nancy; Dykstra, Holly; Weksler, Babette B; Romero, Ignacio A; Couraud, Pierre O; Persidsky, Yuri

    2009-12-01

    Methamphetamine (METH), a potent stimulant with strong euphoric properties, has a high abuse liability and long-lasting neurotoxic effects. Recent studies in animal models have indicated that METH can induce impairment of the blood-brain barrier (BBB), thus suggesting that some of the neurotoxic effects resulting from METH abuse could be the outcome of barrier disruption. In this study, we provide evidence that METH alters BBB function through direct effects on endothelial cells and explore possible underlying mechanisms leading to endothelial injury. We report that METH increases BBB permeability in vivo, and exposure of primary human brain microvascular endothelial cells (BMVEC) to METH diminishes the tightness of BMVEC monolayers in a dose- and time-dependent manner by decreasing the expression of cell membrane-associated tight junction (TJ) proteins. These changes were accompanied by the enhanced production of reactive oxygen species, increased monocyte migration across METH-treated endothelial monolayers, and activation of myosin light chain kinase (MLCK) in BMVEC. Antioxidant treatment attenuated or completely reversed all tested aspects of METH-induced BBB dysfunction. Our data suggest that BBB injury is caused by METH-mediated oxidative stress, which activates MLCK and negatively affects the TJ complex. These observations provide a basis for antioxidant protection against brain endothelial injury caused by METH exposure.

  1. Estimates of Shear Stress and Measurements of Water Levels in the Lower Fox River near Green Bay, Wisconsin

    USGS Publications Warehouse

    Westenbroek, Stephen M.

    2006-01-01

    Turbulent shear stress in the boundary layer of a natural river system largely controls the deposition and resuspension of sediment, as well as the longevity and effectiveness of granular-material caps used to cover and isolate contaminated sediments. This report documents measurements and calculations made in order to estimate shear stress and shear velocity on the Lower Fox River, Wisconsin. Velocity profiles were generated using an acoustic Doppler current profiler (ADCP) mounted on a moored vessel. This method of data collection yielded 158 velocity profiles on the Lower Fox River between June 2003 and November 2004. Of these profiles, 109 were classified as valid and were used to estimate the bottom shear stress and velocity using log-profile and turbulent kinetic energy methods. Estimated shear stress ranged from 0.09 to 10.8 dynes per centimeter squared. Estimated coefficients of friction ranged from 0.001 to 0.025. This report describes both the field and data-analysis methods used to estimate shear-stress parameters for the Lower Fox River. Summaries of the estimated values for bottom shear stress, shear velocity, and coefficient of friction are presented. Confidence intervals about the shear-stress estimates are provided.

  2. A stress-controlled shear cell for small-angle light scattering and microscopy

    NASA Astrophysics Data System (ADS)

    Aime, S.; Ramos, L.; Fromental, J. M.; Prévot, G.; Jelinek, R.; Cipelletti, L.

    2016-12-01

    We develop and test a stress-controlled, parallel plates shear cell that can be coupled to an optical microscope or a small angle light scattering setup, for simultaneous investigation of the rheological response and the microscopic structure of soft materials under an imposed shear stress. In order to minimize friction, the cell is based on an air bearing linear stage, the stress is applied through a contactless magnetic actuator, and the strain is measured through optical sensors. We discuss the contributions of inertia and of the small residual friction to the measured signal and demonstrate the performance of our device in both oscillating and step stress experiments on a variety of viscoelastic materials.

  3. Measurement of turbulent wall shear-stress using micro-pillars

    NASA Astrophysics Data System (ADS)

    Gnanamanickam, E. P.; Nottebrock, B.; Große, S.; Sullivan, J. P.; Schröder, W.

    2013-12-01

    In experimental fluid mechanics, measuring spatially and temporally resolved wall shear-stress (WSS) has proved a challenging problem. The micro-pillar shear-stress sensor (MPS3) has been developed with the goal of filling this gap in measurement techniques. The MPS3 comprises an array of flexible micro-pillars flush mounted on the wall of a wall-bounded flow field. The deflection of these micro-pillars in the presence of a shear field is a direct measure of the WSS. This paper presents the MPS3 development work carried out by RWTH Aachen University and Purdue University. The sensor concept, static and dynamic characterization and data reduction issues are discussed. Also presented are demonstrative experiments where the MPS3 was used to measure the WSS in both water and air. The salient features of the measurement technique, sensor development issues, current capabilities and areas for improvement are highlighted.

  4. [Determining wall shear stress in artificial blood pumps of heart assist devices].

    PubMed

    Debaene, P; Aguilera, D; Kertzscher, U; Affeld, K

    2002-01-01

    The walls in blood pumps are made of artificial material and thus are thrombogenic to a lesser or larger degree. Also the flow plays a role: a blood flow with no flow separations and stagnation zones is required to avoid the generation of thrombi. A precondition for solving this problem is the assessment of the wall shear rate. However this parameter is difficult to assess because of the deformability of the walls and the pulsation of the flow. Two methods are proposed to estimate the wall shear stress in bloodpumps. The paint erosion method allows a characterisation of the flow near the wall. The second method is a special development of standard Particle Image Velocimetry (PIV). A vector field of the flow close to the wall results. Both methods should permit the assessment of the wall shear stress in bloodpumps.

  5. Moderate endurance exercise in patients with sickle cell anaemia: effects on oxidative stress and endothelial activation.

    PubMed

    Faes, Camille; Balayssac-Siransy, Edwige; Connes, Philippe; Hivert, Ludovic; Danho, Clotaire; Bogui, Pascal; Martin, Cyril; Pialoux, Vincent

    2014-01-01

    Very few studies have investigated the effects of exercise on the biological parameters involved in vaso-occlusive events in sickle cell anaemia (SCA). The aim of this study was to test how a mild-moderate endurance exercise modulates oxidative stress, nitric oxide bioavailability and endothelial activation in SCA patients and healthy individuals. Eleven patients with SCA and 15 healthy subjects completed a 20-min duration submaximal cycling exercise at ≈45 Watts. Plasma markers of oxidative stress, antioxidant activity, endothelial activation and nitric oxide bioavailability were investigated before and after the exercise. Nitric oxide levels, anti-oxidant capacity, soluble (s)E-selectin and sP-selectin did not change in response to this exercise. Except for the malondialdehyde levels, which increased in the two groups, the other markers of oxidative stress remained unchanged in both groups in response to exercise. Soluble vascular cell adhesion molecule 1 levels were increased at the end of exercise in both groups. sL-selectin decreased and soluble intercellular adhesion molecule 1 increased with exercise in SCA patients only. The present data suggest that patients with SCA may undertake mild-moderate physical activities without any acute clinical complications, but care should be taken because oxidative stress and endothelial activation significantly increased in some patients.

  6. Infliximab improves endothelial dysfunction in a mouse model of antiphospholipid syndrome: Role of reduced oxidative stress.

    PubMed

    Benhamou, Ygal; Miranda, Sébastien; Armengol, Guillaume; Harouki, Najah; Drouot, Laurent; Zahr, Noel; Thuillez, Christian; Boyer, Olivier; Levesque, Hervé; Joannides, Robinson; Richard, Vincent

    2015-08-01

    Antiphospholipid syndrome (APS), induces endothelial dysfunction, oxidative stress and systemic inflammation that may be mediated by TNFα. Thus, we investigated the possible protective effect of the anti-TNFα antibody infliximab (5μg/g) on endothelial function in a mouse APS model (induced by injection of purified human anti-β2GP1-IgG). Seven days after anti-β2GPI-IgG injection, we observed an increase in plasma sVCAM-1 and sE-selectin levels and in aortic mRNA expression of VCAM-1 and E-selectin. This was associated with a decreased endothelium-dependent relaxation of isolated mesenteric arteries to acetylcholine, together with decreased mesenteric eNOS mRNA expression and increased eNOS uncoupling, accompanied by increased iNOS and gp91phox mRNA and increased left ventricular GSH/GSSH ratio. Infliximab significantly improved the NO-mediated relaxing responses to acetylcholine, and induced a decrease in iNOS and gp91phox mRNA expression. The õpro-adhesive and pro-coagulant phenotypes induced by the anti-β2GP1-IgG were also reversed. This study provides the first evidence that TNFα antagonism improves endothelial dysfunction in APS and suggests that endothelial dysfunction is mediated by TNFα and oxidative stress. Therefore, infliximab may be of special relevance in clinical practice.

  7. Cell-matrix adhesion characterization using multiple shear stress zones in single stepwise microchannel

    NASA Astrophysics Data System (ADS)

    Kim, Min-Ji; Doh, Il; Bae, Gab-Yong; Cha, Hyuk-Jin; Cho, Young-Ho

    2014-08-01

    This paper presents a cell chip capable to characterize cell-matrix adhesion by monitoring cell detachment rate. The proposed cell chip can supply multiple levels of shear stress in single stepwise microchannel. As epithelial-mesenchymal transition (EMT), one of hallmarks of cancer metastasis is closely associated to the interaction with extracelluar matrix (ECM), we took advantage of two lung cancer cell models with different adhesion properties to ECM depending their epithelial or mesenchymal properties, including the pair of lung cancer cells with (A549sh) or without E-cadherin expression (A549sh-Ecad), which would be optimal model to examine the alteration of adhesion properties after EMT induction. The cell-matrix adhesion resisting to shear stress appeared to be remarkably differed between lung cancer cells. The detachment rate of epithelial-like H358 and mesenchymal-like H460 cells was 53%-80% and 25%-66% in the shear stress range of 34-60 dyn/cm2, respectively. A549sh-Ecad cells exhibits lower detachment rate (5%-9%) compared to A549sh cells (14%-40%). By direct comparison of adhesion between A549sh and A549sh-Ecad, we demonstrated that A549shE-cad to mimic EMT were more favorable to the ECM attachment under the various levels of shear stress. The present method can be applied to quantitative analysis of tumor cell-ECM adhesion.

  8. Fluid shear stress stimulates MATE2-K expression via Nrf2 pathway activation.

    PubMed

    Fukuda, Yasunori; Kaishima, Misato; Ohnishi, Toshiyuki; Tohyama, Kimio; Chisaki, Ikumi; Nakayama, Yusuke; Ogasawara-Shimizu, Mari; Kawamata, Yuji

    2017-03-04

    Accurate prediction of drug-induced renal toxicity is necessary for development of safer drugs for patients. Cellular assay systems that recapitulate physiologically relevant microenvironments have been proposed for correct estimation of drug responses in the human body. However, establishment of such assay systems for accurate prediction of renal toxicity is challenging because of the lack of readily available in vitro assay systems. In this study, we investigated the cellular response to fluid shear stress, which is a characteristic of the environment in the kidney proximal tubules, using microfluidic devices. The global gene expression profiles of human primary proximal tubule cells under the fluidic conditions revealed upregulation of MATE2-K and activation of Nrf2 signaling in response to fluid shear stress. Network and cell biological analysis additionally showed that expression of MATE2-K is regulated by Nrf2 signaling. These results strongly suggest that fluid shear stress is involved in the expression and maintenance of function of tissue-specific drug transporters in the proximal tubule, where the cells are exposed to continuous shear stress by primary urine. Furthermore, the microfluidic culture of human proximal tubules was demonstrated to be a useful system to analyze the regulatory mechanisms of gene expression in physiologically relevant cell conditions.

  9. Direct Measurement Sensor of the Boundary Shear Stress in Fluid Flow

    NASA Technical Reports Server (NTRS)

    Badescu, Mircea; Bao, Xiaoqi; Bar-Cohen, Yoseph; Chang, Zensheu; Kerenyi, Kornel; Lih, Shyh-Shiuh; Sherrit, Stewart; Trease, Brian P.; Widholm, Scott

    2010-01-01

    The flow fields and boundary erosion that are associated with scour at bridge piers are very complex. Direct measurement of the boundary shear stress and boundary pressure fluctuations in experimental scour research has always been a challenge and high spatial resolution and fidelity have been almost impossible. Most researchers have applied an indirect process to determine shear stress using precise measured velocity profiles. Laser Doppler Anemometry and Particle Image Velocimetry are common techniques used to accurately measure velocity profiles. These methods are based on theoretical assumptions to estimate boundary shear stress. In addition, available turbulence models cannot very well account for the effect of bed roughness which is fundamentally important for any CFD simulation. The authors have taken on the challenge to advance the magnitude level to which direct measurements of the shear stress in water flow can be performed. This paper covered the challenges and the efforts to develop a higher accuracy and small spatial resolution sensor. Also, preliminary sensor designs and test results are presented.

  10. Cloning the Gravity and Shear Stress Related Genes from MG-63 Cells by Subtracting Hybridization

    NASA Astrophysics Data System (ADS)

    Zhang, Shu; Dai, Zhong-quan; Wang, Bing; Cao, Xin-sheng; Li, Ying-hui; Sun, Xi-qing

    2008-06-01

    Background The purpose of the present study was to clone the gravity and shear stress related genes from osteoblast-like human osteosarcoma MG-63 cells by subtractive hybridization. Method MG-63 cells were divided into two groups (1G group and simulated microgravity group). After cultured for 60 h in two different gravitational environments, two groups of MG-63 cells were treated with 1.5Pa fluid shear stress (FSS) for 60 min, respectively. The total RNA in cells was isolated. The gravity and shear stress related genes were cloned by subtractive hybridization. Result 200 clones were gained. 30 positive clones were selected using PCR method based on the primers of vector and sequenced. The obtained sequences were analyzed by blast. changes of 17 sequences were confirmed by RT-PCR and these genes are related to cell proliferation, cell differentiation, protein synthesis, signal transduction and apoptosis. 5 unknown genes related to gravity and shear stress were found. Conclusion In this part of our study, our result indicates that simulated microgravity may change the activities of MG-63 cells by inducing the functional alterations of specific genes.

  11. Diagnostics of boundary layer transition by shear stress sensitive liquid crystals

    NASA Astrophysics Data System (ADS)

    Shapoval, E. S.

    2016-10-01

    Previous research indicates that the problem of boundary layer transition visualization on metal models in wind tunnels (WT) which is a fundamental question in experimental aerodynamics is not solved yet. In TsAGI together with Khristianovich Institute of Theoretical and Applied Mechanics (ITAM) a method of shear stress sensitive liquid crystals (LC) which allows flow visualization was proposed. This method allows testing several flow conditions in one wind tunnel run and does not need covering the investigated model with any special heat-insulating coating which spoils the model geometry. This coating is easily applied on the model surface by spray or even by brush. Its' thickness is about 40 micrometers and it does not spoil the surface quality. At first the coating obtains some definite color. Under shear stress the LC coating changes color and this change is proportional to shear stress. The whole process can be visually observed and during the tests it is recorded by camera. The findings of the research showed that it is possible to visualize boundary layer transition, flow separation, shock waves and the flow image on the whole. It is possible to predict that the proposed method of shear stress sensitive liquid crystals is a promise for future research.

  12. In vitro shear stress-induced platelet activation: sensitivity of human and bovine blood.

    PubMed

    Lu, Qijin; Hofferbert, Bryan V; Koo, Grace; Malinauskas, Richard A

    2013-10-01

    As platelet activation plays a critical role in physiological hemostasis and pathological thrombosis, it is important in the overall hemocompatibility evaluation of new medical devices and biomaterials to assess their effects on platelet function. However, there are currently no widely accepted in vitro test methods to perform this assessment. In an effort to develop effective platelet tests for potential use in medical device evaluation, this study compared the sensitivity of platelet responses to shear stress stimulation of human and bovine blood using multiple platelet activation markers. Fresh whole blood samples anticoagulated with heparin or anticoagulant citrate dextrose, solution A (ACDA) were exposed to shear stresses up to 40 Pa for 2 min using a cone-and-plate rheometer model. Platelet activation was characterized by platelet counts, platelet surface P-selectin expression, and serotonin release into blood plasma. The results indicated that exposure to shear stresses above 20 Pa caused significant changes in all three of the platelet markers for human blood and that the changes were usually greater with ACDA anticoagulation than with heparin. In contrast, for bovine blood, the markers did not change with shear stress stimulation except for plasma serotonin in heparin anticoagulated blood. The differences observed between human and bovine platelet responses suggest that the value of using bovine blood for in vitro platelet testing to evaluate devices may be limited.

  13. Influence of shear stress magnitude and direction on atherosclerotic plaque composition

    PubMed Central

    Mehta, Vikram V.; Bovens, Sandra M.; Mohri, Zahra; Poulsen, Christian Bo; Gsell, Willy; Tremoleda, Jordi L.; Towhidi, Leila; de Silva, Ranil; Petretto, Enrico; Krams, Rob

    2016-01-01

    The precise flow characteristics that promote different atherosclerotic plaque types remain unclear. We previously developed a blood flow-modifying cuff for ApoE−/− mice that induces the development of advanced plaques with vulnerable and stable features upstream and downstream of the cuff, respectively. Herein, we sought to test the hypothesis that changes in flow magnitude promote formation of the upstream (vulnerable) plaque, whereas altered flow direction is important for development of the downstream (stable) plaque. We instrumented ApoE−/− mice (n = 7) with a cuff around the left carotid artery and imaged them with micro-CT (39.6 µm resolution) eight to nine weeks after cuff placement. Computational fluid dynamics was then performed to compute six metrics that describe different aspects of atherogenic flow in terms of wall shear stress magnitude and/or direction. In a subset of four imaged animals, we performed histology to confirm the presence of advanced plaques and measure plaque length in each segment. Relative to the control artery, the region upstream of the cuff exhibited changes in shear stress magnitude only (p < 0.05), whereas the region downstream of the cuff exhibited changes in shear stress magnitude and direction (p < 0.05). These data suggest that shear stress magnitude contributes to the formation of advanced plaques with a vulnerable phenotype, whereas variations in both magnitude and direction promote the formation of plaques with stable features. PMID:27853578

  14. In Vitro Bone Cell Models: Impact of Fluid Shear Stress on Bone Formation

    PubMed Central

    Wittkowske, Claudia; Reilly, Gwendolen C.; Lacroix, Damien; Perrault, Cecile M.

    2016-01-01

    This review describes the role of bone cells and their surrounding matrix in maintaining bone strength through the process of bone remodeling. Subsequently, this work focusses on how bone formation is guided by mechanical forces and fluid shear stress in particular. It has been demonstrated that mechanical stimulation is an important regulator of bone metabolism. Shear stress generated by interstitial fluid flow in the lacunar-canalicular network influences maintenance and healing of bone tissue. Fluid flow is primarily caused by compressive loading of bone as a result of physical activity. Changes in loading, e.g., due to extended periods of bed rest or microgravity in space are associated with altered bone remodeling and formation in vivo. In vitro, it has been reported that bone cells respond to fluid shear stress by releasing osteogenic signaling factors, such as nitric oxide, and prostaglandins. This work focusses on the application of in vitro models to study the effects of fluid flow on bone cell signaling, collagen deposition, and matrix mineralization. Particular attention is given to in vitro set-ups, which allow long-term cell culture and the application of low fluid shear stress. In addition, this review explores what mechanisms influence the orientation of collagen fibers, which determine the anisotropic properties of bone. A better understanding of these mechanisms could facilitate the design of improved tissue-engineered bone implants or more effective bone disease models. PMID:27896266

  15. Influence of shear stress magnitude and direction on atherosclerotic plaque composition.

    PubMed

    Pedrigi, Ryan M; Mehta, Vikram V; Bovens, Sandra M; Mohri, Zahra; Poulsen, Christian Bo; Gsell, Willy; Tremoleda, Jordi L; Towhidi, Leila; de Silva, Ranil; Petretto, Enrico; Krams, Rob

    2016-10-01

    The precise flow characteristics that promote different atherosclerotic plaque types remain unclear. We previously developed a blood flow-modifying cuff for ApoE(-/-) mice that induces the development of advanced plaques with vulnerable and stable features upstream and downstream of the cuff, respectively. Herein, we sought to test the hypothesis that changes in flow magnitude promote formation of the upstream (vulnerable) plaque, whereas altered flow direction is important for development of the downstream (stable) plaque. We instrumented ApoE(-/-) mice (n = 7) with a cuff around the left carotid artery and imaged them with micro-CT (39.6 µm resolution) eight to nine weeks after cuff placement. Computational fluid dynamics was then performed to compute six metrics that describe different aspects of atherogenic flow in terms of wall shear stress magnitude and/or direction. In a subset of four imaged animals, we performed histology to confirm the presence of advanced plaques and measure plaque length in each segment. Relative to the control artery, the region upstream of the cuff exhibited changes in shear stress magnitude only (p < 0.05), whereas the region downstream of the cuff exhibited changes in shear stress magnitude and direction (p < 0.05). These data suggest that shear stress magnitude contributes to the formation of advanced plaques with a vulnerable phenotype, whereas variations in both magnitude and direction promote the formation of plaques with stable features.

  16. Assessment of shear stress related parameters in the carotid bifurcation using mouse-specific FSI simulations.

    PubMed

    De Wilde, David; Trachet, Bram; Debusschere, Nic; Iannaccone, Francesco; Swillens, Abigail; Degroote, Joris; Vierendeels, Jan; De Meyer, Guido R Y; Segers, Patrick

    2016-07-26

    The ApoE(-)(/)(-) mouse is a common small animal model to study atherosclerosis, an inflammatory disease of the large and medium sized arteries such as the carotid artery. It is generally accepted that the wall shear stress, induced by the blood flow, plays a key role in the onset of this disease. Wall shear stress, however, is difficult to derive from direct in vivo measurements, particularly in mice. In this study, we integrated in vivo imaging (micro-Computed Tomography-µCT and ultrasound) and fluid-structure interaction (FSI) modeling for the mouse-specific assessment of carotid hemodynamics and wall shear stress. Results were provided for 8 carotid bifurcations of 4 ApoE(-)(/)(-) mice. We demonstrated that accounting for the carotid elasticity leads to more realistic flow waveforms over the complete domain of the model due to volume buffering capacity in systole. The 8 simulated cases showed fairly consistent spatial distribution maps of time-averaged wall shear stress (TAWSS) and relative residence time (RRT). Zones with reduced TAWSS and elevated RRT, potential indicators of atherosclerosis-prone regions, were located mainly at the outer sinus of the external carotid artery. In contrast to human carotid hemodynamics, no flow recirculation could be observed in the carotid bifurcation region.

  17. Microflow-induced shear stress on biomaterial wall by ultrasound-induced encapsulated microbubble oscillation

    NASA Astrophysics Data System (ADS)

    Hu, Ji-Wen; Qian, Sheng-You; Sun, Jia-Na; Lü, Yun-Bin; Hu, Ping

    2015-09-01

    A model of an ultrasound-driven encapsulated microbubble (EMB) oscillation near biomaterial wall is presented and used for describing the microflow-induced shear stress on the wall by means of a numerical method. The characteristic of the model lies in the explicit treatment of different types of wall for the EMB responses. The simulation results show that the radius-time change trends obtained by our model are consistent with the existing models and experimental results. In addition, the effect of the elastic wall on the acoustic EMB response is stronger than that of the rigid wall, and the shear stress on the elastic wall is larger than that of the rigid wall. The closer the EMB to the wall, the greater the shear stress on the wall. The substantial shear stress on the wall surface occurs inside a circular zone with a radius about two-thirds of the bubble radius. This paper may be of interest in the study of potential damage mechanisms to the microvessel for drug and gene delivery due to sonoporation. Projects supported by the National Natural Science Foundation of China (Grant Nos. 11174077 and 11474090), the Natural Science Foundation of Hunan Province, China (Grant No. 13JJ3076), the Science Research Program of Education Department of Hunan Province, China (Grant No. 14A127), and the Doctoral Fund of University of South China (Grant No. 2011XQD46).

  18. Analysis on the effect of geometrical design parameters on maximum shear stresses in an electromagnetic micropump

    NASA Astrophysics Data System (ADS)

    Al-Halhouli, A. T.

    2010-02-01

    In this work, the concept of recently introduced electromagnetic pump has been presented. This pump has been proposed for pumping biomedical fluids carrying particles sensitive to shear stresses. Its working concept depends on controlling the rotation of two pistons placed in a circular channel in opposing polarity under the influence of a moving electromagnetic field. Analytical and numerical investigations on the effect of pump geometrical parameters on shear stresses at different boundary conditions are performed. The geometrical parameters include: channel aspect ratio (channel width to height) and channel radius ratio (inner to outer radius). Non-dimensional simple analytical shear stress expressions that are valid for a wide range of geometrical design parameters and variety of fluids are derived. CFD simulations have been used to verify the analytical expressions within the range of studied parameters. Obtained results showed that the analytical models predict the wall maximum shear stresses with an error less than 5% for w / h<=1.0 at high radius ratios and with an error less than10% for Ri / Ro >=0.3. These results help the designer in fabricating the micropump to be suitable for biomedical applications, where saving the particles carried in fluids from damage is of high importance.

  19. The effect of roughness elements on wind erosion: The importance of surface shear stress distribution

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Representation of surface roughness effects on aeolian sediment transport is a key source of uncertainty in wind erosion models. Drag partitioning schemes are used to account for roughness by scaling the soil entrainment threshold by the ratio of shear stress on roughness elements to that on the veg...

  20. Development of a MEMS dual-axis differential capacitance floating element shear stress sensor

    SciTech Connect

    Barnard, Casey; Griffin, Benjamin

    2015-09-01

    A single-axis MEMS wall shear stress sensor with differential capacitive transduction method is produced. Using a synchronous modulation and demodulation interface circuit, the system is capable of making real time measurements of both mean and fluctuating wall shear stress. A sensitivity of 3.44 mV/Pa is achieved, with linearity in response demonstrated up to testing limit of 2 Pa. Minimum detectable signals of 340 μPa at 100 Hz and 120 μPa at 1 kHz are indicated, with a resonance of 3.5 kHz. Multiple full scale wind tunnel tests are performed, producing spectral measurements of turbulent boundary layers in wind speeds ranging up to 0.5 Ma (18 Pa of mean wall shear stress). The compact packaging allows for minimally invasive installation, and has proven relatively robust over multiple testing events. Temperature sensitivity, likely due to poor CTE matching of packaged materials, is an ongoing concern being addressed. These successes are being directly leveraged into a development plan for a dual-axis wall shear stress sensor, capable of producing true vector estimates at the wall.

  1. Oscillatory motion based measurement method and sensor for measuring wall shear stress due to fluid flow

    DOEpatents

    Armstrong, William D.; Naughton, Jonathan; Lindberg, William R.

    2008-09-02

    A shear stress sensor for measuring fluid wall shear stress on a test surface is provided. The wall shear stress sensor is comprised of an active sensing surface and a sensor body. An elastic mechanism mounted between the active sensing surface and the sensor body allows movement between the active sensing surface and the sensor body. A driving mechanism forces the shear stress sensor to oscillate. A measuring mechanism measures displacement of the active sensing surface relative to the sensor body. The sensor may be operated under periodic excitation where changes in the nature of the fluid properties or the fluid flow over the sensor measurably changes the amplitude or phase of the motion of the active sensing surface, or changes the force and power required from a control system in order to maintain constant motion. The device may be operated under non-periodic excitation where changes in the nature of the fluid properties or the fluid flow over the sensor change the transient motion of the active sensor surface or change the force and power required from a control system to maintain a specified transient motion of the active sensor surface.

  2. Molecular Dynamics Study for Channel Size Dependence of Shear Stress Between Droplet and Wall.

    PubMed

    Fukushima, Akinori; Mima, Toshiki; Kinefuchi, Ikuya; Tokumasu, Takashi

    2015-04-01

    In this study, the channel size dependence of the shear stress between water droplets and solid walls in nm-order channel was analyzed. We considered a several different-sized and highly hydrophobic channel whose macroscopic contact angle was about 150 degrees. We have evaluated the shear stress and the normal pressure by molecular dynamics simulation. Analyzing shear stress and normal pressure based on the macroscopic model, we have discussed the difference between the macroscopic model based on hydrodynamics and the microscopic model. As a result, in the high hydrophobic case, it became clear that the shear stress depends on the channel size due to the large Laplace pressure. Furthermore, in the case that the channel size was less than 50 A, the normal pressure by the molecular simulation didn't agree with the expected value from the Young-Laplace equation. From this study it was clear that molecular simulation is needed when the channel size is less than 40 A.

  3. Shear stress tolerance of Streptococcus mutans aggregates determined by microfluidic funnel device (μFFD).

    PubMed

    Shumi, Wahhida; Kim, So Hyun; Lim, Jeesun; Cho, Kyung-Suk; Han, Hwataik; Park, Sungsu

    2013-05-01

    Dental caries are initiated by the attachment of Streptococcus mutans aggregates to the surface of teeth. Bacterial adhesion to the interproximal space, the space between adjacent teeth, has not been investigated due to the lack of devices that mimic the space. Herein, we describe a method for determining the effect of shear stress and sucrose on the attachment of S. mutans aggregates to the interproximal space using microfluidic funnel device (μFFD). Using μFFD, the shear stress tolerance of sucrose-independent and sucrose-dependent S. mutans aggregates (larger than 50 μm in diameter) trapped in the funnel was tested against various flow rates of saliva solution (5 to 50 μl/min). Sucrose-independent aggregates were completely removed from the funnel walls at a low flow rate (10 μl/min) within 7 min., while sucrose-dependent aggregates were removed from the walls only at higher flow rates (25 and 50 μl/min) within several minutes. These results suggest that sucrose-dependent aggregates are more tolerant of shear stress than sucrose-independent aggregates, and are more likely to remain in the region with the smallest shear stress in the teeth.

  4. Field observations of bed shear stress and sediment resuspension on continental shelves, Alaska and California

    USGS Publications Warehouse

    Drake, D.E.; Cacchione, D.A.

    1986-01-01

    Bed shear stress was estimated using wave and current measurements obtained with the GEOPROBE bottom-tripod system during resuspension events in Norton Sound, Alaska, and on the northern California shelf. The boundary-layer model of Grant and Madsen (1979, Journal of Geophysical Research, 84, 1797-1808) was used to compute the bed shear stress under combined wave-generated and quasi-steady currents. Resuspension events were identified by sudden, large increases in light scattering at 1.9 m above the sea floor. The shear-stress values were used to compute the Shields parameter (??). The results for Norton Sound are in excellent agreement with the Shields threshold criterion; the data for the California shelf plot somewhat above the Shields threshold curve, though generally within the scatter envelope. Although the surface sediments in each area contain substantial fine-grained fractions (mean diameters were 0.007 cm in Norton Sound and 0.002 cm on the California shelf), the results do not indicate significant cohesion, because the sediment was entrained at bed shear-stress values close to those predicted by the modified Shields curve for cohesionless fine-grained particles. We suspect that frequent wave stirring and observed plowing of the surface sediment by benthonic animals maintain a high water content and contribute to the ease with which these materials are resuspended. ?? 1986.

  5. Cultivation of shear stress sensitive and tolerant microalgal species in a tubular photobioreactor equipped with a centrifugal pump.

    PubMed

    Michels, Michiel H A; van der Goot, Atze Jan; Vermuë, Marian H; Wijffels, René H

    The tolerance to shear stress of Tetraselmis suecica, Isochrysis galbana, Skeletonema costatum, and Chaetoceros muelleri was determined in shear cylinders. The shear tolerance of the microalgae species strongly depends on the strain. I. galbana, S. costatum, and C. muelleri exposed to shear stress between 1.2 and 5.4 Pa resulted in severe cell damage. T. suecica is not sensitive to stresses up to 80 Pa. The possibility to grow these algae in a tubular photobioreactor (PBR) using a centrifugal pump for recirculation of the algae suspension was studied. The shear stresses imposed on the algae in the circulation tubes and at the pressure side of the pump were 0.57 and 1.82 Pa, respectively. The shear stress tolerant T. suecica was successfully cultivated in the PBR. Growth of I. galbana, S. costatum, and C. muelleri in the tubular PBR was not observed, not even at the lowest pumping speed. For the latter shear sensitive strains, the encountered shear stress levels were in the order of magnitude of the determined maximum shear tolerance of the algae. An equation was used to simulate the effect of possible damage of microalgae caused by passages through local high shear zones in centrifugal pumps on the total algae culture in the PBR. This simulation shows that a culture of shear stress sensitive species is bound to collapse after only limited number of passages, confirming the importance of considering shear stress as a process parameter in future design of closed PBRs for microalgal cultivation.

  6. Quantification of Shear Deformations and Corresponding Stresses in the Biaxially Tested Human Myocardium.

    PubMed

    Sommer, Gerhard; Haspinger, Daniel Ch; Andrä, Michaela; Sacherer, Michael; Viertler, Christian; Regitnig, Peter; Holzapfel, Gerhard A

    2015-10-01

    One goal of cardiac research is to perform numerical simulations to describe/reproduce the mechanoelectrical function of the human myocardium in health and disease. Such simulations are based on a complex combination of mathematical models describing the passive mechanical behavior of the myocardium and its electrophysiology, i.e., the activation of cardiac muscle cells. The problem in developing adequate constitutive models is the shortage of experimental data suitable for detailed parameter estimation in specific functional forms. A combination of shear and biaxial extension tests with different loading protocols on different specimen orientations is necessary to capture adequately the direction-dependent (orthotropic) response of the myocardium. In most experimental animal studies, where planar biaxial extension tests on the myocardium have been conducted, the generated shear stresses were neither considered nor discussed. Hence, in this study a method is presented which allows the quantification of shear deformations and related stresses. It demonstrates an approach for experimenters as to how the generation of these shear stresses can be minimized during mechanical testing. Experimental results on 14 passive human myocardial specimens, obtained from nine human hearts, show the efficiency of this newly developed method. Moreover, the influence of the clamping technique of the specimen, i.e., the load transmission between the testing device and the tissue, on the stress response is determined by testing an isotropic material (Latex). We identified that the force transmission between the testing device and the specimen by means of hooks and cords does not influence the performed experiments. We further showed that in-plane shear stresses definitely exist in biaxially tested human ventricular myocardium, but can be reduced to a minimum by preparing the specimens in an appropriate manner. Moreover, we showed whether shear stresses can be neglected when performing

  7. Some constraints on levels of shear stress in the crust from observations and theory.

    USGS Publications Warehouse

    McGarr, A.

    1980-01-01

    In situ stress determinations in North America, southern Africa, and Australia indicate that on the average the maximum shear stress increases linearly with depth to at least 5.1 km measured in soft rock, such as shale and sandstone, and to 3.7 km in hard rock, including granite and quartzite. Regression lines fitted to the data yield gradients of 3.8 MPa/km and 6.6 MPa/km for soft and hard rock, respectively. Generally, the maximum shear stress in compressional states of stress for which the least principal stress is oriented near vertically is substantially greater than in extensional stress regimes, with the greatest principal stress in a vertical direction. The equations of equilibrium and compatibility can be used to provide functional constrains on the state of stress. If the stress is assumed to vary only with depth z in a given region, then all nonzero components must have the form A + Bz, where A and B are constants which generally differ for the various components. - Author

  8. A simple model to understand the role of membrane shear elasticity and stress-free shape on the motion of red blood cells in shear flow

    NASA Astrophysics Data System (ADS)

    Viallat, Annie; Abkarian, Manouk; Dupire, Jules

    2015-11-01

    The analytical model presented by Keller and Skalak on the dynamics of red blood cells in shear flow described the cell as a fluid ellipsoid of fixed shape. It was extended to introduce shear elasticity of the cell membrane. We further extend the model when the cell discoid physiological shape is not a stress-free shape. We show that spheroid stress-free shapes enables fitting experimental data with values of shear elasticity typical to that found with micropipettes and optical tweezers. For moderate shear rates (when RBCs keep their discoid shape) this model enables to quantitatively determine an effective cell viscosity, that combines membrane and hemoglobin viscosities and an effective shear modulus of the membrane that combines shear modulus and stress-free shape. This model allows determining RBC mechanical parameters both in the tanktreading regime for cells suspended in a high viscosity medium, and in the tumbling regime for cells suspended in a low viscosity medium. In this regime,a transition is predicted between a rigid-like tumbling motion and a fluid-like tumbling motion above a critical shear rate, which is directly related to the mechanical parameters of the cell. A*MIDEX (n ANR-11-IDEX-0001-02) funded by the ''Investissements d'Avenir'', Region Languedoc-Roussillon, Labex NUMEV (ANR-10-LABX-20), BPI France project DataDiag.

  9. Flow separation and shear stress over angle-of-repose bed forms: A numerical investigation

    NASA Astrophysics Data System (ADS)

    Lefebvre, Alice; Paarlberg, Andries J.; Winter, Christian

    2014-02-01

    Large asymmetric bed forms commonly develop in rivers. The turbulence associated with flow separation that develops over their steep lee side is responsible for the form shear stress which can represent a substantial part of total shear stress in rivers. This paper uses the Delft3D modeling system to investigate the effects of bed form geometry and forcing conditions on flow separation length and associated turbulence, and bed form shear stress over angle-of-repose (30° lee side angle) bed forms. The model was validated with lab measurements that showed sufficient agreement to be used for a systematic analysis. The influence of flow velocity, bed roughness, relative height (bed form height/water depth), and aspect ratio (bed form height/length) on the variations of the normalized length of the flow separation zone, the extent of the wake region (where the turbulent kinetic energy (TKE) was more than 70% of the maximum TKE), the average TKE within the wake region and the form shear stress were investigated. Form shear stress was found not to scale with the size of the flow separation zone but to be related to the product of the normalized extent of the wake region (extent of the wake region/extent of water body above the bed form) and the average TKE within the wake region. The results add to understanding of the hydrodynamics of bed forms and may be used for the development of better parameterizations of small-scale processes for application in large-scale studies.

  10. Effects of wall shear stress and its gradient on tumor cell adhesion in curved microvessels.

    PubMed

    Yan, W W; Cai, B; Liu, Y; Fu, B M

    2012-05-01

    Tumor cell adhesion to vessel walls in the microcirculation is one critical step in cancer metastasis. In this paper, the hypothesis that tumor cells prefer to adhere at the microvessels with localized shear stresses and their gradients, such as in the curved microvessels, was examined both experimentally and computationally. Our in vivo experiments were performed on the microvessels (post-capillary venules, 30-50 μm diameter) of rat mesentery. A straight or curved microvessel was cannulated and perfused with tumor cells by a glass micropipette at a velocity of ~1mm/s. At less than 10 min after perfusion, there was a significant difference in cell adhesion to the straight and curved vessel walls. In 60 min, the averaged adhesion rate in the curved vessels (n = 14) was ~1.5-fold of that in the straight vessels (n = 19). In 51 curved segments, 45% of cell adhesion was initiated at the inner side, 25% at outer side, and 30% at both sides of the curved vessels. To investigate the mechanical mechanism by which tumor cells prefer adhering at curved sites, we performed a computational study, in which the fluid dynamics was carried out by the lattice Boltzmann method , and the tumor cell dynamics was governed by the Newton's law of translation and rotation. A modified adhesive dynamics model that included the influence of wall shear stress/gradient on the association/dissociation rates of tumor cell adhesion was proposed, in which the positive wall shear stress/gradient jump would enhance tumor cell adhesion while the negative wall shear stress/gradient jump would weaken tumor cell adhesion. It was found that the wall shear stress/gradient, over a threshold, had significant contribution to tumor cell adhesion by activating or inactivating cell adhesion molecules. Our results elucidated why the tumor cell adhesion prefers to occur at the positive curvature of curved microvessels with very low Reynolds number (in the order of 10(-2)) laminar flow.

  11. Control of circumferential wall stress and luminal shear stress within intact vascular segments perfused ex vivo.

    PubMed

    El-Kurdi, Mohammed S; Vipperman, Jeffrey S; Vorp, David A

    2008-10-01

    Proportional, integral, and derivative (PID) controllers have proven to be robust in controlling many applications, and remain the most widely used control system architecture. The purpose of this work was to use this architecture for designing and tuning two PID controllers. The first was used to control the physiologic arterial circumferential wall stress (CWS) and the second to control the physiologic arterial shear stress (SS) imposed on intact vascular segments that were implanted into an ex vivo vascular perfusion system (EVPS). In order to most accurately control the stresses imposed onto vascular segments perfused ex vivo, analytical models were derived to calculate the CWS and SS. The mid-vein-wall CWS was calculated using the classical Lame solution for thick-walled cylinders in combination with the intraluminal pressure and outer diameter measurements. Similarly, the SS was calculated using the Hagen-Poiseuille equation in combination with the flow rate and outer diameter measurements. Performance of each controller was assessed by calculating the root mean square of the error (RMSE) between the desired and measured process variables. The performance experiments were repeated ten times (N=10) and an average RMSE was reported for each controller. RMSE standard deviations were calculated to demonstrate the reproducibility of the results. Sterile methods were utilized for making blood gas and temperature measurements in order to maintain physiologic levels within the EVPS. Physiologic blood gases (pH, pO(2), and pCO(2)) and temperature within the EVPS were very stable and controlled manually. Blood gas and temperature levels were recorded hourly for several (N=9) 24 h perfusion experiments. RMSE values for CWS control (0.427+/-0.027 KPa) indicated that the system was able to generate a physiologic CWS wave form within 0.5% error of the peak desired CWS over each cardiac cycle. RMSE values for SS control (0.005+/-0.0007 dynescm(2)) indicated that the system

  12. Application of a Reynolds stress turbulence model to the compressible shear layer

    NASA Technical Reports Server (NTRS)

    Sarkar, S.; Balakrishnan, L.

    1990-01-01

    Theoretically based turbulence models have had success in predicting many features of incompressible, free shear layers. However, attempts to extend these models to the high-speed, compressible shear layer have been less effective. In the present work, the compressible shear layer was studied with a second-order turbulence closure, which initially used only variable density extensions of incompressible models for the Reynolds stress transport equation and the dissipation rate transport equation. The quasi-incompressible closure was unsuccessful; the predicted effect of the convective Mach number on the shear layer growth rate was significantly smaller than that observed in experiments. Having thus confirmed that compressibility effects have to be explicitly considered, a new model for the compressible dissipation was introduced into the closure. This model is based on a low Mach number, asymptotic analysis of the Navier-Stokes equations, and on direct numerical simulation of compressible, isotropic turbulence. The use of the new model for the compressible dissipation led to good agreement of the computed growth rates with the experimental data. Both the computations and the experiments indicate a dramatic reduction in the growth rate when the convective Mach number is increased. Experimental data on the normalized maximum turbulence intensities and shear stress also show a reduction with increasing Mach number.

  13. Dynamic and shear stress rheological properties of guar galactomannans and its hydrolyzed derivatives.

    PubMed

    Hussain, Majid; Bakalis, Serafim; Gouseti, Ourania; Zahoor, Tahir; Anjum, Faqir Muhammad; Shahid, Muhammad

    2015-01-01

    Guar galactomannan from seed of Cyamopsis tetragonolobus was hydrolyzed using acid (HCl), base [Ba(OH)2] and enzyme (mannanase) method to obtain depolymerized substances with possible functional applications as soluble dietary fiber. Rheological behavior of crude, purified, and depolymerized guar gum solutions was studied at 25 °C, using shear stress and dynamic oscillatory measurements, performed with controlled stress rheometer Bohlin CVO (Malvern Instruments) fitted with cone-and-plate geometry. The various guar gums solutions with different viscosities exhibited shear-thinning behavior at high shear rate and Newtonian behavior at low shear rate. At low shear rate, sigma crude guar gum (SCGG), crude guar gum (CGG), acid hydrolyzed guar gum (AHGG) and enzyme hydrolyzed guar gum (EHGG) exhibited viscosities of 18.59, 1.346, 0.149 and 0.022 Pas, respectively. Oscillatory experiments (G", G') of gums solutions showed typical behavior of weak viscoelastic gel. All investigated guar gums were further used for glucose bio-accessibility using a novel in vitro small intestinal model (SIM). All gums solutions resulted in 20% reduction in simulated glucose absorption, indicating a non-significant functionality difference between various guar gums. So, it can be concluded that hydrolyzed guar gums without disturbing their rheological and physiological behavior would be useful for incorporation in various food products as soluble dietary fiber.