The mechanisms linking shear stress, endothelial physiology and plaque biology are currently poorly understood, but their elucidation could identify new strategies to reduce plaque growth and ...rupture. To address this, we use eNOS as high shear stress marker coupled to immunofluorescent staining, optical clearing and light-sheet microscopy, to develop a system for analysing the spatial distribution of proteins in murine plaques and correlate them with local WSS.ResultsConfocal microscopy of concavity mounted slides revealed strong eNOS staining at the outer curvature of WT mice but significantly reduced staining at the inner curvature (N=5; P<0.001). This is consistent with high WSS induction of eNOS because the outer curvature corresponds to a HSS site (Suo et al) however precise correlations between eNOS and shear stress could not be made because the tissue geometry was lost during processing.Light-sheet microscopy of cleared samples with preserved 3D structure confirmed elevated expression of eNOS at HSS regions of the outer curvature (figure 1A; N=5 WT; P<0.01). In aortic arches of ApoE-/- mice, eNOS was observed at the outer curvature but was also present at portions of atherosclerotic plaques (figure 1B). Further analysis revealed that eNOS expression was higher at the proximal (upstream) part of the plaque compared to distal (downstream) suggesting a potential correlation with WSS (figure 1C).Abstract BS30 Figure 1Conflict of InterestAtherosclerosis
Glucocorticoid-induced osteoporosis serves as a primary cause for secondary osteoporosis and fragility fractures, representing the most prevalent adverse reaction associated with prolonged ...glucocorticoid use. In this study, to elucidate the impact and underlying mechanisms of fluid shear stress (FSS)-mediated Piezo1 on dexamethasone (Dex)-induced apoptosis, we respectively applied Dex treatment for 6 hours, FSS at 9 dyne/cm2 for 30 minutes, Yoda1 treatment for 2 hours, and Piezo1 siRNA transfection to intervene in MLO-Y4 osteocytes. Western blot analysis was used to assess the expression of Cleaved Caspase-3, Bax, Bcl-2, and proteins associated with the PI3K/Akt pathway. Additionally, qRT-PCR was utilized to quantify the mRNA expression levels of these molecules. Hoechst 33258 staining and flow cytometry were utilized to evaluate the apoptosis levels. The results indicate that FSS at 9 dyne/cm2 for 30 minutes significantly upregulates Piezo1 in osteocytes. Following Dex-induced apoptosis, the phosphorylation levels of PI3K and Akt are markedly suppressed. FSS-mediated Piezo1 exerts a protective effect against Dex-induced apoptosis by activating the PI3K/Akt pathway. Additionally, downregulating the expression of Piezo1 in osteocytes using siRNA exacerbates Dex-induced apoptosis. To further demonstrate the role of the PI3K/Akt signaling pathway, after intervention with the PI3K pathway inhibitor, the activation of the PI3K/Akt pathway by FSS-mediated Piezo1 in osteocytes was significantly inhibited, reversing the anti-apoptotic effect. This study indicates that under FSS, Piezo1 in MLO-Y4 osteocytes is significantly upregulated, providing protection against Dex-induced apoptosis through the activation of the PI3K/Akt pathway.
•FSS-mediated Piezo1 reverses Dex-induced osteocyte apoptosis;•Dex-induced osteocytes apoptosis is achieved through the inhibition of the PI3K/Akt signaling pathway;•The anti-apoptotic effect of FSS-mediated Piezo1 is achieved through activation of the PI3K/Akt signaling pathway.
Response of cells and tissues to shear stress Espina, Jaime A.; Cordeiro, Marilia H.; Milivojevic, Milan ...
Journal of cell science,
09/2023, Volume:
136, Issue:
18
Journal Article
Peer reviewed
Open access
ABSTRACT
Shear stress is essential for normal physiology and malignancy. Common physiological processes – such as blood flow, particle flow in the gut, or contact between migratory cell clusters and ...their substrate – produce shear stress that can have an impact on the behavior of different tissues. In addition, shear stress has roles in processes of biomedical interest, such as wound healing, cancer and fibrosis induced by soft implants. Thus, understanding how cells react and adapt to shear stress is important. In this Review, we discuss in vivo and in vitro data obtained from vascular and epithelial models; highlight the insights these have afforded regarding the general mechanisms through which cells sense, transduce and respond to shear stress at the cellular levels; and outline how the changes cells experience in response to shear stress impact tissue organization. Finally, we discuss the role of shear stress in collective cell migration, which is only starting to be appreciated. We review our current understanding of the effects of shear stress in the context of embryo development, cancer and fibrosis, and invite the scientific community to further investigate the role of shear stress in these scenarios.
IntroductionIt is unknown why aneurysm rupture occurs at a specific location in the aneurysm wall.Aim of StudyPerform a comprehensive analysis of brain aneurysms. This includes aneurysmal wall ...enhancement (AWE), computational fluid dynamics (CFD) and finite element analysis (FEA) of different areas of the aneurysm.MethodsForty-seven unruptured saccular aneurysm were included in the study. 3T high resolution vessel wall imaging was performed. 3D Segmentations of the aneurysms were generated with 3D Slicer to assess: AWE using post-contrast signal intensity (SI) heatmaps; Wall Tension (WT) calculated from FEA; time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and wall shear stress gradient (WSSG) from CFD. A detailed compartmental analysis was performed.ResultsEighteen aneurysms were irregular and eleven had blebs. WT, TAWSS, and WSSG were higher in the neck compared to the dome (p<0.001, p=0.02 and p<0.001, respectively). Conversely, AWE and OSI were higher in the dome compared to the neck (p=0.01 and p=0.03, respectively). In aneurysms with blebs, WT, WSSG, and AWE were significantly different between the bleb, neck, and aneurysm body (p<0.001, p=0.04 and p=0.03, respectively). Blebs had the highest AWE in the aneurysm. However, the lowest points of WT and WSSG in the aneurysms were in the bleb.ConclusionA comprehensive morphomechanical assessment may identify high risk areas of rupture within the aneurysm. Unstable areas, such as blebs, had a high AWE and low WSSG and WT. The morphomechanical features also differed in the aneurysm neck compared to the body.Disclosure of InterestNothing to disclose
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The effect of Y addition on the slip behavior of an edge dislocation on basal, prismatic and second-order pyramidal slip planes of Mg has been investigated using a molecular dynamics ...simulation. It is found that Y increases the critical resolved shear stress of basal slip more than that of non-basal slip and eventually reduces the difference in the CRSS between different slip systems, which is proposed as the reason for the experimentally reported activation of 〈c+a〉 slip in Mg–Y alloys.
Correct FRP tensile specimen Zhavyrkin, V V; Polilov, A N; Arutjunova, A S ...
IOP conference series. Materials Science and Engineering,
01/2020, Volume:
747, Issue:
1
Journal Article
Peer reviewed
Open access
The article depicts a problem of creating a correct composite tensile specimen. Loading of the sample was carried out by shear stresses applied on the gripping part of its lateral surface. The ...calculation of the stress state of the object of study was carried out with the use of ANSYS software. The results obtained were compared with a standard flat sample.
Atherosclerosis is an inflammatory disease that develops preferentially at bends and branches of the vasculature exposed to disturbed flow and low shear stress (LSS). These mechanical conditions ...modify endothelial cell (EC) physiology by regulating proliferation, inflammation and other fundamental processes. Shear stress alters multiple transcriptional programs, including those regulated by the NF-κB family of transcription factors. Although some members of the NF-κB pathway are known to respond to shear, the influence of this haemodynamic force on the c-Rel NF-κB subunit and its role in atherogenesis are still unknown.The expression and function of c-Rel was studied using human umbilical vein EC (HUVEC) and human coronary artery EC (HCAEC) exposed to LSS or high shear stress (HSS) using in vitro flow systems. Western blotting revealed that LSS strongly induced c-Rel expression in HUVEC and HCAEC. Gene silencing coupled to transcriptome profiling demonstrated that c-Rel promotes pathogenic EC processes (inflammation, proliferation) via induction of p38 MAP kinase and non-canonical p100/p52 NF-κB signalling.Consistently, immunofluorescent en face staining of murine aortas revealed a striking enrichment of c-Rel at LSS regions compared to HSS regions. Genetic deletion of c-Rel, either specifically in EC or in the whole body, rescued EC function, reduced arterial inflammation and decreased atherosclerotic lesion area in hypercholesterolemic AAV-PCSK9-treated mice, indicating that c-Rel promotes atherosclerosis by inducing EC pathological changes.Our data demonstrate that c-Rel promotes EC pathophysiological changes at LSS regions and is a driver of atherosclerosis via activation of MAPK and non-canonical NF-κB pathways. These data identify c-Rel as a novel therapeutic target to reduce atherosclerosis.
The estimation of boundary shear stress distribution in a channel is a challenge in some hydraulic or environment investigations. A new partition model of a trapezoidal cross-section in a prismatic ...channel with composite roughness has been introduced based on a concept of a standardized cross-section using the “zero-shear stress” division lines. Based on this new model, an “equal local-region velocity” assumption, which can be regarded as an improvement of Einstein’s (1942) “equal velocity” assumption, has been proposed that is based on a discussion on the mechanism of energy transfer and velocity distribution at two sides of a dividing line. This assumption along with some empirical treatments have been employed to establish a new method to estimate the boundary shear stress of a side-wall or bed. Comparisons show that the proposed method can be applied to composite roughness cases and provides better prediction performance compared to other methods.
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