An experimental investigation of flexural and inter laminar shear stress on hybrid polymer based composites (E glass fibre – Kevlar fibre with Epoxy resin 5052) for different thickness

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.

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Laminar Shear Stress Inhibits Endothelial Cell Metabolism via KLF2-Mediated Repression of PFKFB3

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.114.304277 ◽

2015 ◽

Vol 35 (1) ◽

pp. 137-145 ◽

Cited By ~ 117

Author(s):

Anuradha Doddaballapur ◽

Katharina M. Michalik ◽

Yosif Manavski ◽

Tina Lucas ◽

Riekelt H. Houtkooper ◽

...

Keyword(s):

Shear Stress ◽

Endothelial Cell ◽

Cell Metabolism ◽

Laminar Shear Stress ◽

Laminar Shear ◽

Endothelial Cell Metabolism

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Endothelial albumin permeability is shear dependent, time dependent, and reversible

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1991.260.6.h1992 ◽

1991 ◽

Vol 260 (6) ◽

pp. H1992-H1996 ◽

Cited By ~ 32

Author(s):

H. Jo ◽

R. O. Dull ◽

T. M. Hollis ◽

J. M. Tarbell

Keyword(s):

Shear Stress ◽

Endothelial Cell ◽

Fluorescein Isothiocyanate ◽

Vascular Wall ◽

Laminar Shear Stress ◽

Aortic Endothelial Cells ◽

Transendothelial Permeability ◽

Steady Laminar Shear Stress ◽

Laminar Shear

Altered permeability of vascular endothelium to macromolecules may play a role in vascular disease as well as vascular homeostasis. Because the shear stress of flowing blood on the vascular wall is known to influence many endothelial cell properties, an in vitro system to measure transendothelial permeability (Pe) to fluorescein isothiocyanate conjugated bovine serum albumin under defined physiological levels of steady laminar shear stress was developed. Bovine aortic endothelial cells grown on polycarbonate filters pretreated with gelatin and fibronectin constituted the model system. Onset of 1 dyn/cm2 shear stress resulted in a Pe rise from 5.1 +/- 1.3 x 10(-6) cm/s to 21.9 +/- 4.6 X 10(-6) cm/s at 60 min (n = 6); while 10 dyn/cm2 shear stress increased Pe from 4.8 +/- 1.5 X 10(-6) cm/s to 50.2 +/- 6.8 X 10(-6) cm/s at 30 min and 49.6 +/- 8.9 X 10(-6) cm/s at 60 (n = 9). Pe returned to preshear values within 120 and 60 min after removal of 1 and 10 dyn/cm2 shear stress, respectively. The data show that endothelial cell Pe in vitro is acutely sensitive to shear stress.

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SENCR stabilizes vascular endothelial cell adherens junctions through interaction with CKAP4

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1810729116 ◽

2018 ◽

Vol 116 (2) ◽

pp. 546-555 ◽

Cited By ~ 28

Author(s):

Qing Lyu ◽

Suowen Xu ◽

Yuyan Lyu ◽

Mihyun Choi ◽

Christine K. Christie ◽

...

Keyword(s):

Shear Stress ◽

Endothelial Cell ◽

Noncoding Rna ◽

Rna Binding ◽

Adherens Junctions ◽

Vascular Endothelial Cell ◽

Membrane Integrity ◽

Laminar Shear Stress ◽

Loss Of Function ◽

Laminar Shear

SENCR is a human-specific, vascular cell-enriched long-noncoding RNA (lncRNA) that regulates vascular smooth muscle cell and endothelial cell (EC) phenotypes. The underlying mechanisms of action of SENCR in these and other cell types is unknown. Here, levels of SENCR RNA are shown to be elevated in several differentiated human EC lineages subjected to laminar shear stress. Increases in SENCR RNA are also observed in the laminar shear stress region of the adult aorta of humanized SENCR-expressing mice, but not in disturbed shear stress regions. SENCR loss-of-function studies disclose perturbations in EC membrane integrity resulting in increased EC permeability. Biotinylated RNA pull-down and mass spectrometry establish an abundant SENCR-binding protein, cytoskeletal-associated protein 4 (CKAP4); this ribonucleoprotein complex was further confirmed in an RNA immunoprecipitation experiment using an antibody to CKAP4. Structure–function studies demonstrate a noncanonical RNA-binding domain in CKAP4 that binds SENCR. Upon SENCR knockdown, increasing levels of CKAP4 protein are detected in the EC surface fraction. Furthermore, an interaction between CKAP4 and CDH5 is enhanced in SENCR-depleted EC. This heightened association appears to destabilize the CDH5/CTNND1 complex and augment CDH5 internalization, resulting in impaired adherens junctions. These findings support SENCR as a flow-responsive lncRNA that promotes EC adherens junction integrity through physical association with CKAP4, thereby stabilizing cell membrane-bound CDH5.

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Endothelial Barrier Function is co-regulated at Vessel Bifurcations by Fluid Forces and Sphingosine-1-Phosphate

10.1101/2020.08.18.256586 ◽

2020 ◽

Author(s):

Ehsan Akbari ◽

Griffin B. Spychalski ◽

Miles M. Menyhert ◽

Kaushik K. Rangharajan ◽

Shaurya Prakash ◽

...

Keyword(s):

Shear Stress ◽

Fluid Flow ◽

Barrier Function ◽

Endothelial Barrier ◽

Laminar Shear Stress ◽

Endothelial Barrier Function ◽

Fluid Forces ◽

Sphingosine 1 Phosphate ◽

Laminar Shear ◽

Vessel Bifurcations

AbstractSphingosine-1-phosphate (S1P) is a blood-borne bioactive lipid mediator of endothelial barrier function. Prior studies have implicated mechanical stimulation due to intravascular laminar shear stress in co-regulating S1P signaling in endothelial cells (ECs). Yet, vascular networks in vivo consist of vessel bifurcations, and this geometry produces hemodynamic forces that are distinct from laminar shear stress. However, the role of these forces at vessel bifurcations in regulating S1P-dependent endothelial barrier function is not known. In this study, we implemented a microfluidic platform that recapitulates the flow dynamics of vessel bifurcations with in situ quantification of the permeability of microvessel analogues. Co-application of S1P with impinging bifurcated fluid flow, which was characterized by approximately zero shear stress and 38 dyn cm-2 stagnation pressure at the vessel bifurcation point, promotes vessel stabilization. Similarly, co-treatment of carrier-free S1P with 3 dyn cm-2 laminar shear stress is also protective of endothelial barrier function. Moreover, it is shown that vessel stabilization due to laminar shear stress, but not bifurcated fluid flow, is dependent on S1P receptor 1 or 2 signaling. Collectively, these findings demonstrate the endothelium-protective function of fluid forces at vessel bifurcations and their involvement in coordinating S1P-dependent regulation of vessel permeability.

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Effects of laminar shear stress on expression of MT1‐MMP in rat bone marrow‐derived mesenchymal stem cells

The FASEB Journal ◽

10.1096/fasebj.26.1_supplement.913.8 ◽

2012 ◽

Vol 26 (S1) ◽

Author(s):

Wang Han Qin

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Shear Stress ◽

Mesenchymal Stem Cells ◽

Laminar Shear Stress ◽

Laminar Shear ◽

Rat Bone

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Primary cilia of human endothelial cells disassemble under laminar shear stress

The Journal of Cell Biology ◽

10.1083/jcb.200312133 ◽

2004 ◽

Vol 164 (6) ◽

pp. 811-817 ◽

Cited By ~ 145

Author(s):

Carlo Iomini ◽

Karla Tejada ◽

Wenjun Mo ◽

Heikki Vaananen ◽

Gianni Piperno

Keyword(s):

Endothelial Cells ◽

Shear Stress ◽

Primary Cilia ◽

Umbilical Vein ◽

Intraflagellar Transport ◽

Mechanical Stimuli ◽

Laminar Shear Stress ◽

Human Endothelial Cells ◽

Umbilical Vein Endothelial Cells ◽

Laminar Shear

We identified primary cilia and centrosomes in cultured human umbilical vein endothelial cells (HUVEC) by antibodies to acetyl-α-tubulin and capillary morphogenesis gene-1 product (CMG-1), a human homologue of the intraflagellar transport (IFT) protein IFT-71 in Chlamydomonas. CMG-1 was present in particles along primary cilia of HUVEC at interphase and around the oldest basal body/centriole at interphase and mitosis. To study the response of primary cilia and centrosomes to mechanical stimuli, we exposed cultured HUVEC to laminar shear stress (LSS). Under LSS, all primary cilia disassembled, and centrosomes were deprived of CMG-1. We conclude that the exposure to LSS ends the IFT in cultured endothelial cells.

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Competing Fluid Forces Control Endothelial Sprouting in a 3-D Microfluidic Vessel Bifurcation Model

Micromachines ◽

10.3390/mi10070451 ◽

2019 ◽

Vol 10 (7) ◽

pp. 451 ◽

Cited By ~ 8

Author(s):

Ehsan Akbari ◽

Griffin B. Spychalski ◽

Kaushik K. Rangharajan ◽

Shaurya Prakash ◽

Jonathan W. Song

Keyword(s):

Shear Stress ◽

Fluid Flow ◽

Bifurcation Point ◽

Flow Dynamics ◽

Laminar Shear Stress ◽

Local Flow ◽

Fluid Forces ◽

Sprouting Angiogenesis ◽

Laminar Shear

Sprouting angiogenesis—the infiltration and extension of endothelial cells from pre-existing blood vessels—helps orchestrate vascular growth and remodeling. It is now agreed that fluid forces, such as laminar shear stress due to unidirectional flow in straight vessel segments, are important regulators of angiogenesis. However, regulation of angiogenesis by the different flow dynamics that arise due to vessel branching, such as impinging flow stagnation at the base of a bifurcating vessel, are not well understood. Here we used a recently developed 3-D microfluidic model to investigate the role of the flow conditions that occur due to vessel bifurcations on endothelial sprouting. We observed that bifurcating fluid flow located at the vessel bifurcation point suppresses the formation of angiogenic sprouts. Similarly, laminar shear stress at a magnitude of ~3 dyn/cm2 applied in the branched vessels downstream of the bifurcation point, inhibited the formation of angiogenic sprouts. In contrast, co-application of ~1 µm/s average transvascular flow across the endothelial monolayer with laminar shear stress induced the formation of angiogenic sprouts. These results suggest that transvascular flow imparts a competing effect against bifurcating fluid flow and laminar shear stress in regulating endothelial sprouting. To our knowledge, these findings are the first report on the stabilizing role of bifurcating fluid flow on endothelial sprouting. These results also demonstrate the importance of local flow dynamics due to branched vessel geometry in determining the location of sprouting angiogenesis.

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