Low Shear Stress Research Articles

β-glycerophosphate, not low magnitude fluid shear stress, increases osteocytogenesis in the osteoblast-to-osteocyte cell line IDG-SW3

ABSTRACT Aim As osteoblasts deposit a mineralized collagen network, a subpopulation of these cells differentiates into osteocytes. Biochemical and mechanical stimuli, particularly fluid shear stress (FSS), are thought to regulate this, but their relative influence remains unclear. Here, we assess both biochemical and mechanical stimuli on long-term bone formation and osteocytogenesis using the osteoblast-osteocyte cell line IDG-SW3. Methods Due to the relative novelty and uncommon culture conditions of IDG-SW3 versus other osteoblast-lineage cell lines, effects of temperature and media formulation on matrix deposition and osteocytogenesis were initially characterized. Subsequently, the relative influence of biochemical (β-glycerophosphate (βGP) and ascorbic acid 2-phosphate (AA2P)) and mechanical stimulation on osteocytogenesis was compared, with intermittent application of low magnitude FSS generated by see-saw rocker. Results βGP and AA2P supplementation were required for mineralization and osteocytogenesis, with 33°C cultures retaining a more osteoblastic phenotype and 37°C cultures undergoing significantly higher osteocytogenesis. βGP concentration positively correlated with calcium deposition, whilst AA2P stimulated alkaline phosphatase (ALP) activity and collagen deposition. We demonstrate that increasing βGP concentration also significantly enhances osteocytogenesis as quantified by the expression of green fluorescent protein linked to Dmp1. Intermittent FSS (~0.06 Pa) rocker had no effect on osteocytogenesis and matrix deposition. Conclusions This work demonstrates the suitability and ease with which IDG-SW3 can be utilized in osteocytogenesis studies. IDG-SW3 mineralization was only mediated through biochemical stimuli with no detectable effect of low magnitude FSS. Osteocytogenesis of IDG-SW3 primarily occurred in mineralized areas, further demonstrating the role mineralization of the bone extracellular matrix has in osteocyte differentiation.

Von Willebrand factor antigen, von Willebrand factor propeptide and ADAMTS13 activity in TIA or ischaemic stroke patients changing antiplatelet therapy

Data are limited on the impact of commencing antiplatelet therapy on von Willebrand Factor Antigen (VWF:Ag) or von Willebrand Factor propeptide (VWFpp) levels and ADAMTS13 activity, and their relationship with platelet reactivity following TIA/ischaemic stroke.In this pilot, observational study, VWF:Ag and VWFpp levels and ADAMTS13 activity were quantified in 48 patients ≤4 weeks of TIA/ischaemic stroke (baseline), and 14 days (14d) and 90 days (90d) after commencing aspirin, clopidogrel or aspirin+dipyridamole. Platelet reactivity was assessed at moderately-high shear stress (PFA-100® Collagen-Epinephrine / Collagen-ADP / INNOVANCE PFA P2Y assays), and low shear stress (VerifyNow® Aspirin / P2Y12, and Multiplate® Aspirin / ADP assays).VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d in the overall population (P ≤ 0.03). In the clopidogrel subgroup, VWF:Ag levels decreased and VWFpp/VWF:Ag ratio increased between baseline and 14d and 90d (P ≤ 0.01), with an increase in ADAMTS13 activity between baseline vs. 90d (P ≤ 0.03). In the aspirin+dipyridamole subgroup, there was an inverse relationship between VWF:Ag and VWFpp levels with both PFA-100 C-ADP and INNOVANCE PFA P2Y closure times (CTs) at baseline (P ≤ 0.02), with PFA-100 C-ADP, INNOVANCE PFA P2Y and C-EPI CTs at 14d (P ≤ 0.05), and between VWF:Ag levels and PFA-100 INNOVANCE PFA P2Y CTs at 90d (P = 0.03). There was a positive relationship between ADAMTS13 activity and PFA-100 C-ADP CTs at baseline (R2 = 0.254; P = 0.04).Commencing/altering antiplatelet therapy, mainly attributed to commencing clopidogrel in this study, was associated with decreasing endothelial activation following TIA/ischaemic stroke. These data enhance our understanding of the impact of VWF:Ag and VWFpp especially on ex-vivo platelet reactivity status at high shear stress after TIA/ischaemic stroke.

Spatial variation in stress orientation in and around Türkiye: rupture propagation across the stress regime transition in the 2023 Mw 7.8 Kahramanmaraş earthquake

SUMMARY On 6 February 2023, the Mw 7.8 Kahramanmaraş, Türkiye, earthquake occurred on the East Anatolian Fault Zone (EAFZ). This study examined the spatial variation of the stress field in and around Türkiye, particularly along the EAFZ, better to understand the rupture process of this event. We first combined focal mechanisms around Türkiye, created a data set consisting of 2984 focal mechanisms, and conducted stress tensor inversion. The results showed that the maximum compressional axis near the EAFZ was oriented north–south and slightly varied along the strike. Moreover, the relative magnitude of north–south compressional stress gradually increased from south to north, and the stress regime changes from a normal fault regime to a strike-slip fault regime. The static stress change caused by the 2023 Mw 7.8 and 7.7 events does not explain this lateral pattern, implying that this stress regime transition existed before the main shock. This suggests that shear stress on the EAFZ was low in this southern segment because it was unfavourably oriented to the regional stress field. Dynamic stress changes due to rupture propagation and dynamic weakening may have triggered the slip at the southern segment under low background shear stress. Previous studies have reported that the Mw 7.8 main shock rupture started at a splay fault, first propagated through the central and northern segments and then backpropagated with a time delay towards the southern segment, where it caused a significant but relatively small slip. The pre-existing along-strike shear stress variation on the fault may have contributed to the smaller and delayed coseismic slip in the southern segment than in the central and northern segments. The main shock rupture possibly caused stress rotation locally near the central segment where the magnitudes of the vertical and north–south compressional stresses were almost equal.

Preparation and Application of Decanoic Acid/Arginine Hydrogels to a Transdermal Formulation.

We prepared a supramolecular hydrogel composed of decanoic acid and arginine (C10/Arg gel) and evaluated its application to a transdermal formulation. C10/Arg gel adjusted to pH 7 with 1 M NaOH aq or 1 M HCl aq provided a translucent hydrogel with a lamellar liquid crystal structure in the concentration region of decanoic acid ≥12% and arginine ≤9%. Rheological measurements showed that C10/Arg gel is a viscoelastic material with both solid and liquid properties, with elasticity being dominant over viscosity in the low shear stress region. The skin permeability of hydrocortisone (HC) and indomethacin (IM) from C10/Arg gels was investigated in vitro using hairless mouse skin and compared to control formulation drug suspensions (IM or HC) in water. The cumulative permeation amount of HC and IM from the C10/Arg gel at 10 h after application was approximately 16 and 11 times higher than that of the control, respectively. On the other hand, the flux of IM decreased with increasing arginine concentration, likely due to the acid-base interaction between Arg and IM in C10/Arg gel. Adequate drug skin permeation enhancement by C10/Arg gel requires optimizing the gel composition for each specific drug.

Fabrication of a novel hydrophobic zinc borate/polydopamine/talc nanocomposite with sandwich-like structure for enhanced tribological properties

Two-dimensional layered materials (2DLMs) as lubricant additives have received increasing attention due to their low interlaminar shear stress, outstanding chemical stability and lubrication effects, but the extreme pressure properties, dispersion and dispersion stability in base oils are poor. Herein, a hydrophobic zinc borate/polydopamine/talc (OA-ZB/PDA/TA) nanocomposite with sandwich-like structure is prepared by hydrothermal-assisted intercalation combined with mechanical activation process using natural talc 2DLMs as substrate and oleic acid (OA) as a surface hydrophobic modifier and peeling aid. No obvious sedimentation of OA-ZB/PDA/TA occurs in the rapeseed oil after 15 d, while pure TA is significantly deposited after 12 h, showing superior dispersion and dispersion stability. The OA-ZB/PDA/TA used as a lubricant additive in rapeseed oil exhibits excellent tribological performances under the loads from 147 to 784 N, particularly, wear scar diameter and coefficient of friction reduce by 51.4 and 33.7 % under 392 N, respectively, and the maximum nonseizure load (PB) increases by 27.0 % relative to pure TA. The TA-ZB-TA "sandwich-like" structure gives full play to the synergistic lubrication between ZB NPs and TA, resulting in the sliding and rolling effects under low load, friction film and rolling effect under medium load, and friction film under high load. Our work provides a new avenue for the enhanced extreme pressure properties and dispersion stability of 2DLMs in base oil.

Ruptured Vertebral Artery Dissection Treated with Endovascular Intervention

A retrospective study of cases of endovascular treatment of dissection of the vertebral artery with subarachnoid hemorrhage was conducted. Data were 11 cases of vertebral artery dissecting aneurysm (VADA) among 291 consecutive subarachnoid hemorrhage patients who underwent clipping or endovascular treatment at Ota Memorial Hospital. Classified into 4 patterns based on the location of the dissection and posterior inferior cerebellar artery (PICA): pre-PICA, post-PICA, involved PICA, and non-PICA. And one of the cases had bilateral vertebral artery dissection, and computational fluid dynamics analysis was included in the study. Ruptured VADA occurred in 11 of the 291 patients (3.8%). Endovascular treatment was performed in 8 of these 11 patients. Postoperative diffusion-weighted imaging detected no high-intensity lesions and no postoperative ischemic complications or rebleeding occurred in any patient. In a case of bilateral VADA, computational fluid dynamics analysis of very low or high wall shear stress at the dissection, low aneurysm formation indicator, and high oscillatory shear index may be considered rupture factors. Treatment strategies for each branching pattern of PICA can prevent rupture and avoid ischemic complications. And prediction of the rupture side is important in patients with bilateral dissection to consider the appropriate treatment and timing.

Preliminary analysis: Effect of a rotary generator of hydrodynamic cavitation on rheology and methane yield of wastewater sludge

Slightly acidic (pH 5.1) waste sludge with 4.7 % Total Solids (TS) was treated on a laboratory scale pined disc rotary generator of hydrodynamic cavitation (PD RGHC). Influence of four rotor discs with different number of cavitation generation units (CGUs) was investigated: 8-pins, 12-pins, 16-pins and 8-prism elements. The effect of hydrodynamic cavitation (HC) was investigated by analyzing rheological properties, surface tension, dewaterability, and particle size distribution. After subjecting the sludge to 30 cavitation passes, the dewatering ability of the sludge significantly decreased, resulting in a more than two-fold increase in Capillary Suction Time (CST). All regimes were successful in disintegrating particles to smaller sizes. A slight increase of sludge surface tension was measured post cavitation. Cavitated samples displayed a zero-shear viscosity, in contrast to the untreated sample, where viscosity noticeably increased as shear stress decreased. HC did not improve methane yield. Statistically significant correlations between physio-chemical properties and apparent viscosity at low shear stress were identified. Although there were no discernible statistical differences in sludge characteristics, some trends are visible among investigated CGU designs and warrant further research.

Atheroprotective WSS effects on human aortic endothelial cells in a new generation bioreactor

Abstract Funding Acknowledgements None. Background Luminal arterial endothelial cells are mainly aligned along the blood flow direction, whereas the in vitro endothelial cells (EC) showed heterogeneous distribution. In atherosclerosis the altered blood flow, acting on mechano-transduction, contributes to endothelial dysfunction and barrier disorganization. A low wall shear stress (WSS) has a pro-atherosclerotic effect, whilst elevated WSS is atheroprotective. Purposes Aim of this work is to study the primary human aortic EC cells (HAOEC) capability to acquire a distribution reminiscent of the luminal alignment under atheroprotective WSS using a prototypal new generation bioreactor. Methods We have developed a novel device compatible with culture inside standard sterile incubator, allowing to apply complex WSS patterns in controlled conditions. The bioreactor includes a sample housing and a parallel plate flow chamber and is controlled by a custom electronic interface actuating motor and pump. The cells were settled over PMMA supports and coating conditions were setup. Atheroprotective WSS patterns were tested. We compared HAOEC submitted to high flow (1.2 Pa for 24h) vs. ramps with different slopes (3h, 8h, 24h) followed by steady-state flow (1.2Pa for 24h, 48h). Viability and distribution of Acridine Orange-labelled HAOEC were assessed over bioreactor supports at both beginning and end of the experiments using fluorescence microscope. Hematoxylin/Eosin and Coomassie Blue staining were tested after the experiment to evaluate the shape and cell orientation (directionality FiJi plugin). Confocal microscopy on HAOEC labelled with Phalloidin–TRITC, anti-CD31/PECAM1-AlexaFluor488 and DAPI displayed the flow-related changes. Results HAOEC settled over naked sterile PMMA supports mainly detached under WSS, independently from the cell number. Coating with extracellular matrix components (i.e., human laminin, bovine fibronectin, chicken collagen type II, human collagen type I) showed the superiority of collagen type I to obtain homogeneously distributed, flow-resistant cell monolayers. In static condition, HAOEC on coated supports demonstrated ≥50% detachment within 24h, those submitted to a direct atheroprotective WSS of 1.2Pa almost completely detached. Consistently, to ramps with high slope (range 0.2-1,2Pa in 3h or 8h) followed by1.2Pa WSS corresponded 60%-90% cell detachment. Conversely, a 24h ramp (range 0.2-1,2Pa) followed by 24h or 48h of 1.2Pa WSS preserved the HAOEC monolayer adherence, and aligned cells were found. Microscopy comparative analysis of selected areas before/after WSS showed a partial spatial reorganization, with changes in the F-actin cytoskeleton and CD31 distribution. Conclusion We have optimized a protocol for studying HAOEC under atheroprotective WSS. In perspective further increasing the duration of the stimulus under constant WSS will achieve full alignment and provide a pseudo-physiologic model for multidirectional atherogenic WSS studies.

Rupture point is associated with divergent hemodynamics in intracranial aneurysms.

Understanding the risk factors leading to intracranial aneurysm (IA) rupture have still not been fully clarified. They are vital for proper medical guidance of patients harboring unruptured IAs. Clarifying the hemodynamics associated with the point of rupture could help could provide useful information about some of the risk factors. Thus far, few studies have studied this issue with often diverging conclusions. We identified a point of rupture in patients operated for an IAs during surgery, using a combination of preoperative computed tomography (CT) and computed tomography angiography (CTA). Hemodynamic parameters were calculated both for the aneurysm sac as a whole and the point of rupture. In two cases, the results of CFD were compared with those of the experiment using particle image velocimetry (PIV). We were able to identify 6 aneurysms with a well-demarcated point of rupture. In four aneurysms, the rupture point was near the vortex with low wall shear stress (WSS) and high oscillatory shear index (OSI). In one case, the rupture point was in the flow jet with high WSS. In the last case, the rupture point was in the significant bleb and no specific hemodynamic parameters were found. The CFD results were verified in the PIV part of the study. Our study shows that different hemodynamic scenarios are associated with the site of IA rupture. The numerical simulations were confirmed by laboratory models. This study further supports the hypothesis that various pathological pathways may lead to aneurysm wall damage resulting in its rupture.

Providing ceramics high-temperature self-lubrication by inducing vacancies concentration variation via thermal and frictional synergies

Based on the new conception of lattice low-shear stress induced by zero-dimensional point defects, the Al2O3 composite ceramics doped by TiO2 with good high-temperature tribological properties are prepared. According to the results, temperature could control the continuity of the resintering friction layer and the activation of the plastic deformation ability of ceramics. The lattice oxygen in TiO2 leaves the original lattice occupation due to thermal and frictional coupling action, and breaks away from the worn surface, which significantly increases the vacancy concentration level. Aforesaid structural defects are considered to be a crucial reason for the reduction of shear force. Compared with friction coefficient (0.53) for Al2O3 at 1100 °C, COF of TiO2-doped Al2O3-based ceramics is 0.26 about half of that. This vacancy quantitative change strategy of temperature-sensibility is expected to become a controllable method for providing lubrication during high-temperature.

Low shear stress-induced blockage of autophagic flux impairs endothelial barrier and facilitates atherosclerosis in mice

Atherosclerosis preferentially occurs in areas with low shear stress (LSS) and oscillatory flow. LSS has been demonstrated to correlate with the development of atherosclerosis. The sphingosine 1-phosphate receptor 1 (S1PR1), involving intravascular blood flow sensing, regulates vascular development and vascular barrier function. However, whether LSS affects atherosclerosis via regulating S1PR1 remains incompletely clear. In this study, immunostaining results of F-actin, β-catenin, and VE-cadherin indicated that LSS impaired endothelial barrier function in human umbilical vein endothelial cells (HUVECs). Western blot analysis showed that LSS resulted in blockage of autophagic flux in HUVECs. In addition, autophagy agonist Rapamycin (Rapa) antagonized LSS-induced endothelial barrier dysfunction, whereas autophagic flux inhibitor Bafilomycin A1 (BafA1) exacerbated it, indicating that LSS promoted endothelial barrier dysfunction by triggering autophagic flux blockage. Notably, gene expression analysis revealed that LSS downregulated S1PR1 expression, which was antagonized by Rapa. Selective S1PR1 antagonist W146 impaired endothelial barrier function of HUVECs under high shear stress (HSS) conditions. Moreover, our data showed that expression of GAPARAPL2, a member of autophagy-related gene 8 (Atg8) proteins, was decreased in HUVECs under LSS conditions. Autophagic flux blockage induced by GAPARAPL2 knockdown inhibited S1PR1, aggravated endothelial barrier dysfunction of HUVECs in vitro, and promoted aortic atherosclerosis in ApoE−/− mice in vivo. Our study demonstrates that autophagic flux blockage induced by LSS downregulates S1PR1 expression and impairs endothelial barrier function. GABARAPL2 inhibition is involved in LSS-induced autophagic flux blockage, which impairs endothelial barrier function via downregulation of S1PR1.

Impact of Anthropogenic Aerosol Transport on Cloud Condensation Nuclei Activity During Summertime in Qilian Mountain, in the Northern Tibetan Plateau

AbstractIn this study, we conducted field campaigns at two mountain‐top observatories on the Qilian Mountains (QLM) in the northeastern Tibetan Plateau of China, which plays a vital role in sustaining water resources for the downstream arid and semi‐arid regions. The two observatories, Waliguan Baseline Observatory (WLG) and Laohugou station (LHG), are situated on the eastern and western edge of the QLM, respectively. The objectives of this study were to examine the properties of atmospheric aerosols, CCN concentrations (NCCN) at varying supersaturation levels (SS = 0.2%–1.0%), and the hygroscopic nature of aerosols in the QLM, especially during the formation of orographic cloud. Notably, the average aerosol concentration and NCCN was approximately 2–3 factors higher at WLG compared to LHG. The chemical compositions of aerosols were primarily dominated by sulfate and organic aerosol (OA) at these two sites. A very high hygroscopicity parameter of aerosol calculated using chemical composition was observed at these two sites (0.37 ± 0.03 at LHG vs. 0.30 ± 0.04 at WLG). Enhanced aerosol loading episodes impacted by anthropogenic emission were observed at these two sites. Exploration on high‐loading cases at each site, we found that the CCN activity was dominated by aerosol size, but the chemical processes of aerosol during the formation of orographic cloud could also be important in CCN activity, especially for low SS conditions. These findings collectively underscore the significant impact of anthropogenic air plumes on CCN concentrations in the QLM and their potential influence on precipitation patterns.

Swimming behaviour of downstream migrating carp in accelerating flows

The downstream migration of fish is impacted by accelerating flow. This study coupled computational fluid dynamics (CFD) modelling and laboratory observations to investigate the effects of two different accelerating flow hydrodynamics on the swimming behaviours of two fish species. The silver carp (Hypophthalmichthys molitrix) and bighead carp (Hypophthalmichthys nobilis) were chosen as target fish species and four hydrodynamic parameters were selected as main indicators to affect fish swimming behaviours. Four specific swimming behaviours were classified in the contraction flume based on fish downstream trajectories. The results indicated that high accelerating flow, low turbulent kinetic energy (Tke ) and shear stress generated the symmetric distribution of fish along two boundaries of the contraction flume. It also indicated that discharge increase would increase the fish entrainment risk from intakes to diversion pipe, while two fish species exhibited different swimming behaviour patterns. Velocity and velocity gradient had more significant effects than other hydrodynamic parameters on fish swimming strategies. There was mutual compensation among fish tail-beat frequency, angle and amplitude. The results illustrated the relationship between the swimming behaviours and hydrodynamics, which could contribute to understanding the fish downstream migration behaviours in accelerating flow.

Differential Distribution and Expression of α1-adrenergic Receptors in Low Shear Stress Induced Neointimal Formation

Low fluid shear stress in conduit arteries has emerged as a determinant of neointimal formation—an accumulation of vascular smooth muscle cells on the surface of the intima—the most challenging component of atherosclerosis to treat. α1-adrenergic receptor (α1-AR) antagonists have been well evaluated in vascular injury models yielding reduced neointimal formation. However, the α1-AR subtypes’ (α1A-AR, α1B-AR, α1D-AR) role in neointimal formation have not been determined under low shear stress conditions. α1-AR subtypes are expressed in various tissues and evoke different responses to the same ligand resulting in both adaptive and maladaptive responses. This study was designed to identify and characterize the α1-AR subtypes in low shear stress induced neointimal formation. An in vivo partial ligation mouse model was utilized to actuate low fluid shear stress and create neointimal formation in the left carotid artery in 14 days. The right carotid artery remained uninjured as the control. For tissue collection and processing, the left and right carotid arteries were harvested, snap-frozen in liquid nitrogen, and cryosectioned. Immunofluorescence staining was performed using primary antibodies for α1B-AR or α1A-AR and CD31 (endothelial cell marker). Confocal microscopy combined with processing and analysis was utilized for the detection, location, and distribution of cell markers. Histomorphometric analysis revealed significant structural changes, including the medial area and neointimal area, between the injured and non-injured arteries at the 14-day timepoint. Moreover, the injured arteries showed an increase in percent area stenosis, compared to the non-injured control. Histological observation of fluorescently labeled images revealed α1B-AR is densely distributed in the neointimal and medial area of the injured carotid arteries compared to the non-injured control. NucBlue (nuclear) staining indicated an increase in cell number in the medial and neointimal areas of the injured artery. Together, these results offer insight into changes in vascular α1-ARs under low shear stress conditions suggesting that α1B-AR may be upregulated in response to injury and contribute to neointimal formation. NIH HL155288. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Biological and Methodological Variability in Retinal Nerve Fiber Layer OCT: The Framingham Heart Study

ObjectiveTo explore participant-level biological attributes and scan-level methodological attributes associated with retinal nerve fiber layer (RNFL) thickness variability in a population-based sample of elderly United States adults. DesignCross-sectional analysis using data from the Framingham Heart Study. Participants1,347 eyes from 825 participants with at least one optical coherence tomography (OCT) scan and axial length data were included. MethodsThree or more successive RNFL scans of each eye of each participant were obtained in a single session. Multivariable linear mixed models were employed to explore the associations between average RNFL thickness with participant-level biological attributes (age, gender, race, ethnicity, and axial length) and scan-level attributes (signal strength [SS]) as independent variables in the whole population as well as a sub-sample of adults with no self-reported history of glaucoma. Similar analyses were designed to assess methodological variability with average within-eye standard deviation (SD) for repeated scans as the dependent variable. Main Outcomes1) Biological variability: average RNFL thickness, 2) Methodological variability: average within- participant SD across repeated scans. ResultsAge (β= −0.19 microns/year, [95% CI: −0.29, −0.09]), female gender (β= +1.48 microns vs. male, [95% CI: 0.09,2.86]), axial length (β= −1.24 microns/mm of greater length, [95% CI: −1.80, −0.67]), and SS (β= +1.62 microns/1 unit greater SS, [95% CI: 1.16,2.09]) were significantly associated with RNFL thickness, while race and ethnicity were not (p>0.05). In analyses designed to assess methodological variability, higher RNFL thickness (β= +0.02 per micron increase, [95% CI: 0.01,0.03]), and lower SS (β= +0.19 per 1 unit lower SS, [95% CI: 0.10,0.27]) were significantly associated with greater RNFL variability. In adults with no self-reported history of glaucoma (n of eyes = 1165, n of participants = 712), female gender was not associated with RNFL, while African-American race was associated with thicker RNFL (β= +4.65 microns vs. Whites, [95% CI: 1.28,8.03]). ConclusionsRNFL thickness is lower with older age, male gender, greater axial length, lower signal strength, and Whites (as compared to African-Americans) without self-reported glaucoma. Measurement variability (SD) is higher with greater RNFL thickness and lower SS. Understanding these biological and methodological variations is important to aid in OCT interpretation.

Abstract 3019: Piezo-1 Expression Decreases Under Disturbed Flow Model Of Femoral Atherosclerosis.

Background: Peripheral arterial disease (PAD) is often manifest by focal atherosclerotic plaque formation in the infra-inguinal arteries. However, murine models of atherosclerosis in the infra-inguinal arteries are lacking. It is well known that low and oscillatory wall shear stress, which occurs around blockages in PAD, promotes focal atherosclerotic plaque, but this has not been tested in vivo. Piezo1 is a mechanosensitive ion channel associated with hemodynamic changes in the arterial wall, but its role in flow-mediated atherosclerotic plaque deposition is not known. Objective: To develop a flow-mediated murine model of focal atherosclerotic plaque in the femoral arteries. Methods: 8 male and female S129 mice underwent partial femoral artery ligation (Figure A/B). Wall shear stress was calculated from duplex ultrasound imaging (Figure C/D). Atherogenic conditions were imposed with PCSK9 infection and high fat diet; this was initiated 1 week prior to partial femoral ligation. Histologic comparison of the left (partial femoral ligation) and right (normal stable flow) was performed. Results: Low wall shear stress was induced in this model (Figure C/D). Piezo1 expression was decreased in both male and female arteries under these conditions in this model (Figure E). Atherosclerotic plaque was induced by the partial femoral artery ligation but not on the normal stable flow side (Figure F). Conclusions: We have successfully developed a flow-mediated model of focal atherosclerotic plaque in murine femoral arteries. This is associated with downregulation of Piezo1 gene expression. Ongoing work is examining the causative role of Piezo1 on endothelial response to disturbed flow.

Sex-Related Differences in Vascular Function Among Older Adults with Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a sleep disorder associated with hypertension and cardiovascular disease (CVD) risk. Endothelial dysfunction and altered shear stress are implicated in OSA-related CVD pathogenesis, however, their contributions to CVD risk in males vs females remains unclear. We obtained measures of resting blood pressure (BP), brachial artery flow-mediated dilation (FMD), brachial artery diameter, and shear stress in 71 older adults (F=30, M=41; age=66.9±7.7) diagnosed with mild, moderate, or severe OSA based on oxygen desaturation index (ODI) score. All were prospective participants in an ongoing clinical trial (NCT04932447). Group differences (mean ± SD) were assessed with two-way ANOVAs (sex X severity) and associations between ODI score, baseline diameter, relative FMD, shear stress, and BP were assessed with Pearson correlations. We hypothesized that a) regardless of sex, individuals with greater OSA severity exhibit lower relative FMD and mean shear stress, greater baseline diameter and higher BP, and b) for a given OSA severity, females have greater relative FMD and mean shear stress and lower baseline diameter and BP compared to males. In line with our hypotheses, we found greater mean shear stress in females compared to males (F=69.6±26.9 s−1, M=53.5±16.7 s−1, p=0.035) and among females, those with mild OSA had higher mean shear stress than those with severe OSA (mild=77.6±26.1 s−1, severe= 44.4±8.5 s−1, p=0.009). Contrary to expectations, mean shear stress did not differ as a function of OSA severity in male subjects, nor was there any difference in FMD or BP across OSA severity between males and females. In subjects with moderate OSA, FMD was greater in females than males (F=6.07±3.89%, M=3.07±2.39%, p=0.047). On average, baseline diameters were larger in adults with severe OSA compared to moderate OSA (moderate=3.66±0.59 mm, severe=4.33±0.61 mm, p=0.003), and females with mild (F=3.20±0.47 mm, M=4.73±0.50 mm, p<0.001) and moderate (F=3.31±0.42 mm, M=3.91±0.57 mm, p=0.007) OSA had smaller baseline diameters than their male counterparts. There were no differences in baseline diameter between males and females with severe OSA. We report a negative correlation between mean shear stress and BP (systolic BP, r=-0.48, p=0.011; diastolic BP, r=-0.55, p=0.002) and a positive correlation between ODI score and baseline diameter (r=0.54, p=0.003) in females but not males. Conversely, ODI score and relative FMD were positively correlated in male subjects (r=0.45, p=0.009), but not females. Overall, our findings highlight sex-specific vascular differences in older adults with OSA. Relative to males, females with mild OSA exhibit greater mean shear stress and lower baseline diameters, which may confer a cardiovascular advantage. In contrast, males and females with severe OSA exhibit similar vascular characteristics. Our findings provide new insights into the impact of sex and OSA severity on vascular function and CVD risk in older adults. This work is supported by NIH/NIA grant number: 1R01AG065346. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effects of freeze-thaw cycles on the tensile properties of geogrids and shear behavior of geogrid-soil interface

The tensile strength of geogrids and the shear strength of the reinforced soil interface are critical technical indicators for designing reinforced soil structures. This study developed a temperature-controlled apparatus to examine the tensile properties of geogrids subjected to freeze-thaw cycles within the soil, and the effect of interface temperature and freeze-thaw cycles on the shear behavior of the geogrid-soil interface. Eight and four groups of direct shear and tensile tests were conducted on the geogrid-soil interface and geogrids, respectively, under varying conditions. The peak tensile strength of geogrids remained similar to that of non-freeze-thaw samples after experiencing freeze–thaw cycles within the soil. tensile properties of geogrids were independent of the number of freeze–thaw cycles. At constant water content (w=6%), the peak shear stress at the geogrid-soil interface decreased by 24% (7 freeze-thaw cycles) compared to the non-freeze-thaw group. The cohesion and friction angle of the geogrid-soil interface decreased with increasing freeze-thaw cycles but tended to stabilize after 4 freeze-thaw cycles. The reinforcement provided by the geogrid enhanced with decrease in the interface temperature. The shear stress was higher at interface temperature under 0 °C, whereas in a non-frozen state, the interface exhibited lower shear stress with a consistent stable value.

Comparative Study of G+6 Irregular Multistoryed Building of L Shape of Diaphragm Discontinuity

Abstract: This study investigates the effectiveness of incorporating roof openings in re-entrant corner plan irregular buildings at various locations under earthquake loads. Three models L-shaped diaphragm discontinuity were analyzed using STAAD Pro software. Node displacement and storey shear in both the X and Z directions were evaluated to assess structural performance. The results indicate that models with square diaphragm discontinuity exhibit increased node displacements and storey shear compared to those with L-shaped diaphragm discontinuity. The model with L-shaped diaphragm discontinuity consistently demonstrates superior performance in terms of lower displacements and shear stress values. However, the final model selection should take into account specific project requirements and design considerations.

Numerical simulation of cellular blood flow in curved micro-vessels with saccular aneurysms: Effect of curvature degree and hematocrit level.

The dynamics of cellular blood flow in curved vessels considerably differ from those in straight vessels. It is reported that clotting development is significantly affected by vessel shape irregularities. Thus, the current study aims to investigate the effect of curvature degree and hematocrit level on cellular blood flow in a curved micro-vessel with a saccular aneurysm. Accordingly, a three-dimensional numerical simulation is performed using a validated code developed for cellular blood flow problems. The obtained results show that the cell-free layer thickness is highly dependent on the curvature degree and hematocrit level, which may have a remarkable impact on the apparent viscosity of blood as well as the dynamics of other particles such as drug particulates. The near-wall region exhibits the highest degree of cell deformation, whereas the red blood cells within the aneurysm zone remain nearly undeformed. Meanwhile, the velocity of the red blood cells decreases with the increase in curvature degree, which can affect the quality of the oxygenation process. Because of the saccular aneurysm, a considerable decrease in plasma velocity is predicted. Moreover, no secondary flows are detected in the curved vessel except in the aneurysm zone. An increase in the curvature degree is expected to reduce the blood flow rate by about 10%. Furthermore, low wall shear stress values are predicted in the straight case compared to the values at the apex of the curved vessel, which may affect the structure and function of the endothelial cells of the vessel wall and, hence, increase the aneurysm rupture possibility.