Blood Flow Shear Stress Research Articles

Influence of disturbed blood flow on endothelial function in people living with HIV

Abstract Introduction People infected with human immunodeficiency virus (HIV) are more susceptible to endothelial dysfunction due to the virus itself, side effects of the antiretroviral therapy and classical risk factors. Endothelial damage is most prominent at the locations where laminar blood flow is disturbed and oscillatory shear stress with retrograde blood flow is dominating. Purpose The goal of this study was to assess the endothelial function in people with HIV, and to determine whether their endothelium is more susceptible to a short-term increase in retrograde blood flow in comparison to healthy individuals. Methods The study included 62 people with HIV infection and 38 people without HIV infection, in whom endothelial function was assessed using flow-mediated dilatation, which was presented in absolute (FMD) and relative (FMD%) values. The intervention produced oscillatory shear stress and retrograde blood flow during 20 minutes, after which the endothelial function assessment was repeated. Results Baseline FMD (0.30±0.07 vs. 0.36±0.07 mm; p<0.05) and FMD% (6.84±1.57 vs. 7.89±1.19 %, p<0.05) were lower in the HIV group in compare to controls. FMD and FMD% decreased in the HIV group by 0.03 mm and 0.7% (p<0.05), while in the control group they decreased by 0.09 mm and 2.0% (p<0.05). The post-intervention FMD and FMD% were not different between the groups (p>0.05). Conclusion People with HIV infection express worse endothelial function in compare to healthy individuals. Retrograde blood flow and oscillatory shear stress deteriorate endothelial function in both HIV patients and healthy controls, although this decline is more pronounced in healthy individuals.

Chemical mapping of the surface interactome of PIEZO1 identifies CADM1 as a modulator of channel inactivation

The propeller-shaped blades of the PIEZO1 and PIEZO2 ion channels partition into the plasma membrane and respond to indentation or stretching of the lipid bilayer, thus converting mechanical forces into signals that can be interpreted by cells, in the form of calcium flux and changes in membrane potential. While PIEZO channels participate in diverse physiological processes, from sensing the shear stress of blood flow in the vasculature to detecting touch through mechanoreceptors in the skin, the molecular details that enable these mechanosensors to tune their responses over a vast dynamic range of forces remain largely uncharacterized. To survey the molecular landscape surrounding PIEZO channels at the cell surface, we employed a mass spectrometry-based proteomic approach to capture and identify extracellularly exposed proteins in the vicinity of PIEZO1. This PIEZO1-proximal interactome was enriched in surface proteins localized to cell junctions and signaling hubs within the plasma membrane. Functional screening of these interaction candidates by calcium imaging and electrophysiology in an overexpression system identified the adhesion molecule CADM1/SynCAM that slows the inactivation kinetics of PIEZO1 with little effect on PIEZO2. Conversely, we found that CADM1 knockdown accelerates inactivation of endogenous PIEZO1 in Neuro-2a cells. Systematic deletion of CADM1 domains indicates that the transmembrane region is critical for the observed effects on PIEZO1, suggesting that modulation of inactivation is mediated by interactions in or near the lipid bilayer.

Biomechanics cerebral and carotid arteries: aneurysm development and atherosclerotic plaque detachment in the presence of combined pathologies

Today, the main cause of mortality in the world remains cardiovascular diseases. In this case, the combined pathology of the neck and head arteries, in which atherosclerosis affects the carotid arteries and there is a change in blood flow in the vertebral arteries or in the circle of Willis due to aplasia of the communicating artery, significantly increases the risk of aneurysms formation and their subsequent rupture. Assessing the risk of complications in this type of pathological condition may allow the physician to initiate timely preventive measures in specific clinical cases. The paper presents the results of modelling various variants of combined pathologies in the arteries of the neck and head. The segment under consideration includes sections of the common carotid, external and internal carotid arteries, as well as vessels of the circle of Willis and the basilar artery. The main idea of the study was to create a prognostic model to assess the risks of aneurysm formation in the circle of Willis and atherosclerotic plaque rupture in the carotid arteries. Such a system may be useful for physicians in routine practice when planning treatment tactics in patients with combined pathologies of the arterial channel. Based on the literature analysis, a number of pathologies of the cerebral and carotid arteries, most frequently occurring in various combinations, were identified: stenoses of the ICA (30 % and 70 %) and aplasia (absence) of one of the connecting arteries were considered from the point of view of geometrical features. In addition, the character of blood flow in the basilar artery, which can change its direction in steal-syndrome, was taken into account. Based on the analysis of blood flow and wall shear stress, two degrees of risk of aneurysm formation were distinguished. High risk corresponds to cases for which both of these values were statistically significantly different from the norm. Medium risk corresponds to cases for which only one of the values was statistically significantly different from the norm. For models containing atherosclerotic plaques, data on shear and normal stresses on the surfaces of atherosclerotic plaques were tabulated. The risk of plaque rupture on each side was determined for each case by analysing the result sets 11 combinations of pathological conditions with increased risk were indicated.

Oscillatory shear stress promotes endothelial senescence and atherosclerosis via STING activation

Endothelial dysfunction is an initiating factor in atherosclerosis. Endothelial cells (ECs) are constantly subject to blood flow shear stress, and atherosclerotic plaques tend to occur in aortic bends or bifurcations impaired by low oscillatory shear stress (OSS). However, the mechanism that how OSS affects the initiation and progression of atherosclerosis remains to be explored. Here, we first reported that OSS can promote endothelial dysfunction and atherogenesis in vivo and in vitro by activating STING pathway. Mechanistically, at atherosclerosis-prone areas, OSS caused mitochondria damage in ECs, leading to the leakage of mitochondrial DNA (mtDNA) into the cytoplasm. The cytoplasmic mtDNA was recognized by cGAS to produce cGAMP, activating the STING pathway and leading to endothelial senescence, which resulted in endothelial dysfunction and atherosclerosis. We found that STING was activated in plaques of atherosclerotic patients and in aortic arch ECs of high-fat diet (HFD)-fed ApoeKO mice, as well as in ECs exposed to OSS. STING-specific deficiency in ECs attenuates endothelial senescence and resulted in a significant reduction in aortic arch plaque area in HFD-fed ApoeKO mice. Consistently, specific deficiency or pharmacological inhibition of STING attenuated OSS-induced senescence and endothelial dysfunction. Pharmacological depletion of mtDNA ameliorated OSS-induced senescence and endothelial dysfunction. Taken together, our study linked hemodynamics and endothelial senescence, and revealed a novel mechanism by which OSS leads to endothelial dysfunction. Our study provided new insights into the development of therapeutic strategies for endothelial senescence and atherosclerosis.

Coronary hemodynamic simulation study.

In this paper, a two-way fluid-structure coupling model is developed to simulate and analyze the hemodynamic process based on dynamic coronary angiography, and examine the influence of different hemodynamic parameters on coronary arteries in typical coronary stenosis lesions. Using the measured FFR pressure data of a patient, the pressure-time function curve is fitted to ensure the accuracy of the boundary conditions. The average error of the simulation pressure results compared to the test data is 6.74%. In addition, the results related to blood flow, pressure contour and wall shear stress contour in a typical cardiac cycle are obtained by simulation analysis. These results are found to be in good agreement with the laws of the real cardiac cycle, which verifies the rationality of the simulation. In conclusion, based on the modeling and hemodynamic simulation analysis process of dynamic coronary angiography, this paper proposes a method to assist the analysis and evaluation of coronary hemodynamic and functional parameters, which has certain practical significance.

Epigenetic changes in shear-stressed endothelial cells.

Epigenetic changes, particularly histone compaction modifications, have emerged as critical regulators in the epigenetic pathway driving endothelial cell phenotype under constant exposure to laminar forces induced by blood flow. However, the underlying epigenetic mechanisms governing endothelial cell behavior in this context remain poorly understood. To address this knowledge gap, we conducted in vitro experiments using human umbilical vein endothelial cells subjected to various tensional forces simulating pathophysiological blood flow shear stress conditions, ranging from normotensive to hypertensive forces. Our study uncovers a noteworthy observation wherein endothelial cells exposed to high shear stress demonstrate a decrease in the epigenetic marks H3K4ac and H3K27ac, accompanied by significant alterations in the levels of HDAC (histone deacetylase) proteins. Moreover, we demonstrate a negative regulatory effect of increased shear stress on HOXA13 gene expression and a concomitant increase in the expression of the long noncoding RNA, HOTTIP, suggesting a direct association with the suppression of HOXA13. Collectively, these findings represent the first evidence of the role of histone-related epigenetic modifications in modulating chromatin compaction during mechanosignaling of endothelial cells in response to elevated shear stress forces. Additionally, our results highlight the importance of understanding the physiological role of HOXA13 in vascular biology and hypertensive patients, emphasizing the potential for developing small molecules to modulate its activity. These findings warrant further preclinical investigations and open new avenues for therapeutic interventions targeting epigenetic mechanisms in hypertensive conditions.

Predicting the Pharmacological Targets of Astragalus membranaceus against Hypertensive Nephropathy

Objective: Hypertension is one of the main causes of chronic kidney disease. Astragalus membranaceus (AM), an important traditional Chinese medicine for treating hypertensive nephropathy, has a complex composition that makes it challenging to explore its mechanism of action and limits its clinical application. This study aims to investigate the underlying mechanism of AM in treating hypertensive nephropathy. Methods: We retrieved all the compound data of AM from the Traditional Chinese Medicine Systems Pharmacology database and screened out the active compounds and their target proteins. Then, a network of candidate compounds and target compounds of AM was constructed using Cytoscape software. Furthermore, hypertensive nephropathy-related genes from the DisGeNET and GeneCards databases were intersected with AM target proteins and hypertensive nephropathy-related genes to determine the potential targets of AM in treating hypertensive nephropathy. Finally, after performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, we conducted molecular docking to verify the interaction between the main active ingredients of AM and the core targets. Results: A total of 87 effective components of AM were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. According to the network of active compounds and their target proteins, 18 of the 20 effective compounds in AM could act on 210 proteins. Taking the intersection of 274 hypertensive nephropathy-related genes and AM target proteins, 49 potential targets of AM in treating hypertensive nephropathy were identified. Using the median degree value, we determined 25 core targets of AM in treating hypertensive nephropathy. GO enrichment analysis showed that the biological processes of AM on hypertensive nephropathy mainly focused on the inflammatory response, hypoxia response, angiogenesis, cell proliferation, and cell migration. KEGG pathway enrichment analysis mainly involved cancer pathways, the AGE-RAGE signaling pathway in diabetic complications, blood flow shear stress, and atherosclerosis. Molecular docking results showed that quercetin, kaempferol, and 7-O-methylisomucronulatol had strong binding activity with several target proteins and may exert protective effects by stabilizing the interaction between molecules through the intermolecular forces of hydrogen bonds. Conclusion: This study reveals the targets of AM in treating hypertensive nephropathy using network pharmacology and molecular docking, providing new clues for developing novel drugs for hypertensive nephropathy and basic research development.

Hemodynamic regulation allows stable growth of microvascular networks

How do vessels find optimal radii? Capillaries are known to adapt their radii to maintain the shear stress of blood flow at the vessel wall at a set point, yet models of adaptation purely based on average shear stress have not been able to produce complex loopy networks that resemble real microvascular systems. For narrow vessels where red blood cells travel in a single file, the shear stress on vessel endothelium peaks sharply when a red blood cell passes through. We show that stable shear-stress-based adaptation is possible if vessel shear stress set points are cued to the stress peaks. Model networks that respond to peak stresses alone can quantitatively reproduce the observed zebrafish trunk microcirculation, including its adaptive trajectory when hematocrit changes or parts of the network are amputated. Our work reveals the potential for mechanotransduction alone to generate stable hydraulically tuned microvascular networks.

Self-Reinforced PTLG Copolymer with Shish Kebab Structures and a Bionic Surface as Bioimplant Materials for Tissue Engineering Applications.

Green and biodegradable materials with great mechanical properties and biocompatibility will offer new opportunities for next-generation high-performance biological materials. Herein, the novel oriented shish kebab crystals of a novel poly(trimethylene carbonate-lactide-glycolide) (PTLG) vascular stent are first reported to be successfully fabricated through a feasible solid-state drawing process to simultaneously enhance the mechanical performance and biocompatibility. The crystal structure of this self-reinforced vascular stent was transformed from spherulites to a shish kebab crystal, which indicates the mechanical interlocking effect and prevents the lamellae from slipping with a significant improvement of mechanical strength to 333 MPa. Meanwhile, it is different from typical biomedical polymers with smooth surface structures, and the as-obtained PTLG vascular stent exhibits a bionic surface morphology with a parallel micro groove and ridge structure. These ridges and grooves were attributed to the reorganization of cytoskeleton fiber bundles following the direction of blood flow shear stress. The structure and parameters of these morphologies were highly similar to the inner surface of blood vessels of the human, which facilitates cell adhesion growth to improve its proliferation, differentiation, and activity on the surface of PTLG.

Enhanced external counterpulsation treatment regulates blood flow and wall shear stress metrics in femoral artery: An in vivo study in healthy subjects

As a non-invasive assisted circulation therapy, enhanced external counterpulsation (EECP) has demonstrated potential in treatment of lower-extremity arterial disease (LEAD). However, the underlying hemodynamic mechanism remains unclear. This study aimed to conduct the first prospective investigation of the EECP-induced responses of blood flow behavior and wall shear stress (WSS) metrics in the femoral artery. Twelve healthy male volunteers were enrolled. A Doppler ultrasound-basedapproach was introduced for the in vivo determination of blood flow in the common femoral artery (CFA) and superficial femoral artery (SFA) during EECP intervention, with incremental treatment pressures ranging from 10 to 40 kPa. Three-dimensional subject-specific numerical models were developed in 6 subjects to quantitatively assess variations in WSS-derived hemodynamic metrics in the femoral bifurcation. A mesh-independence analysis was performed. Our results indicated that, compared to the pre-EECP condition, both the antegrade and retrograde blood flow volumes in the CFA and SFA were significantly augmented during EECP intervention, while the heart rate remained constant. The time average shear stress (TAWSS) over the entire femoral bifurcation increased by 32.41%, 121.30%, 178.24%, and 214.81% during EECP with treatment pressures of 10 kPa, 20 kPa, 30 kPa, and 40 kPa, respectively. The mean relative resident time (RRT) decreased by 24.53%, 61.01%, 69.81%, and 77.99%, respectively. The percentage of area with low TAWSS in the femoral artery dropped to nearly zero during EECP with a treatment pressure greater than or equal to 30 kPa. We suggest that EECP is an effective and non-invasive approach for regulating blood flow and WSS in lower extremity arteries.

Modulation of red blood cell nitric oxide synthase phosphorylation in the quiescent and exercising human forearm.

In vitro investigations demonstrate that human erythrocytes synthesize nitric oxide via a functional isoform of endothelial nitric oxide synthase (NOS) (RBC-NOS). We tested the hypothesis that phosphorylation of RBC-NOS at serine residue 1177 (RBC-NOS1177) would be amplified in blood draining-active skeletal muscle. Furthermore, given hypoxemia modulates local blood flow and thus shear stress, and nitric oxide availability, we performed duplicate experiments under normoxia and hypoxia. Nine healthy volunteers performed rhythmic handgrip exercise at 60% of individualized maximal workload for 3.5 min while breathing room air (normoxia) and after being titrated to an arterial oxygen saturation ≈80% (hypoxemia). We measured brachial artery blood flow by high-resolution duplex ultrasound, while continuously monitoring vascular conductance and mean arterial pressure using finger photoplethysmography. Blood was sampled during the final 30 s of each stage from an indwelling cannula. Blood viscosity was measured to facilitate calculation of accurate shear stresses. Erythrocytes were assessed for levels of phosphorylated RBC-NOS1177 and cellular deformability from blood collected at rest and during exercise. Forearm exercise increased blood flow, vascular conductance, and vascular shear stress, which coincided with a 2.7 ± 0.6-fold increase in RBC-NOS1177 phosphorylation (P < 0.0001) and increased cellular deformability (P < 0.0001) under normoxia. When compared with normoxia, hypoxemia elevated vascular conductance and shear stress (P < 0.05) at rest, while cellular deformability (P < 0.01) and RBC-NOS1177 phosphorylation (P < 0.01) increased. Hypoxemic exercise elicited further increases in vascular conductance, shear stress, and cell deformability (P < 0.0001), although a subject-specific response in RBC-NOS1177 phosphorylation was observed. Our data yield novel insights into the manner that hemodynamic force and oxygen tension modulate RBC-NOS in vivo.

Image-based flow simulation of platelet aggregates under different shear rates.

Hemodynamics is crucial for the activation and aggregation of platelets in response to flow-induced shear. In this paper, a novel image-based computational model simulating blood flow through and around platelet aggregates is presented. The microstructure of aggregates was captured by two different modalities of microscopy images of in vitro whole blood perfusion experiments in microfluidic chambers coated with collagen. One set of images captured the geometry of the aggregate outline, while the other employed platelet labelling to infer the internal density. The platelet aggregates were modelled as a porous medium, the permeability of which was calculated with the Kozeny-Carman equation. The computational model was subsequently applied to study hemodynamics inside and around the platelet aggregates. The blood flow velocity, shear stress and kinetic force exerted on the aggregates were investigated and compared under 800 s-1, 1600 s-1 and 4000 s-1 wall shear rates. The advection-diffusion balance of agonist transport inside the platelet aggregates was also evaluated by local Péclet number. The findings show that the transport of agonists is not only affected by the shear rate but also significantly influenced by the microstructure of the aggregates. Moreover, large kinetic forces were found at the transition zone from shell to core of the aggregates, which could contribute to identifying the boundary between the shell and the core. The shear rate and the rate of elongation flow were investigated as well. The results imply that the emerging shapes of aggregates are highly correlated to the shear rate and the rate of elongation. The framework provides a way to incorporate the internal microstructure of the aggregates into the computational model and yields a better understanding of the hemodynamics and physiology of platelet aggregates, hence laying the foundation for predicting aggregation and deformation under different flow conditions.

Wall shear rate and energy loss coefficient measures using conventional Doppler ultrasound do not predict carotid plaque progression.

Background: The rate of carotid plaque progression is believed to be related to blood flow hemodynamics and shear stress. Our objective was to determine if wall shear rate (WSR) and the energy loss coefficient (ELC) measured by Doppler ultrasound could predict atherosclerotic carotid disease progression. Patients and methods: Patients at a large tertiary center with an initial ultrasound between 2016 and 2018 with a significant carotid plaque were included if they had at least one 6 months follow-up comparative study. Stenosis progression was assessed according to the NASCET (The North American Symptomatic Carotid Endarterectomy Trial) percentage criterion. Results: The average annual progression rate for the 74 plaques included was 5.7% NASCET per year. We identified 18 plaques with ≥10% NASCET progression and 56 plaques without significant progression <10% NASCET. Among the plaques with progression, only four plaques had progression greater than 20% NASCET. Median WSR was 6266 s-1 [5813-8974] in plaques with progression and 6564 s-1 [5285-8766] in stable plaques (p=0.643). Median ELC was 3.86 m2 [2.78-5.53] in plaque with progression and 4.32 m2 [3.42-6.81] in stable plaques (p=0.296). Conclusions: Although it is a widely accepted hypothesis that shear stress and hemodynamics of the carotid bifurcation contribute to plaque progression, we found that WSR and ELC estimated by Doppler ultrasound do not reliably predict atherosclerotic plaque progression in the carotid artery. Other ultrasound modalities, such as 3D imaging, may be used to assess the influence of plaque geometry and hemodynamics in plaque progression.

Computational Fluid Dynamics (CFD) Model for Analysing the Role of Shear Stress in Angiogenesis in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease characterised by an attack on healthy cells in the joints. Blood flow and wall shear stress are crucial in angiogenesis, contributing to RA's pathogenesis. Vascular endothelial growth factor (VEGF) regulates angiogenesis, and shear stress is a surrogate for VEGF in this study. Our objective was to determine how shear stress correlates with the location of new blood vessels and RA progression. To this end, two models were developed using computational fluid dynamics (CFD). The first model added new blood vessels based on shear stress thresholds, while the second model examined the entire blood vessel network. All the geometries were based on a micrograph of RA blood vessels. New blood vessel branches formed in low shear regions (0.840-1.260 Pa). This wall-shear-stress overlap region at the junctions was evident in all the models. The results were verified quantitatively and qualitatively. Our findings point to a relationship between the development of new blood vessels in RA, the magnitude of wall shear stress and the expression of VEGF.

High-Resolution Hemodynamic Analysis of a Wearable Oxygenator Using High-Performance Computing

In this paper, we study the hydrodynamics of a wearable oxygenator using computational fluid dynamics on a supercomputer. In this computation, the fiber bundle of the oxygenator is modeled by a porous medium model, and the incompressible Navier-Stokes equations with a K-ε turbulence model are used to model the flow in the channels. The blood flow velocity, pressure, and shear stress are carefully studied and the hemolysis index of the oxygenator NIH is calculated by using the fast three-dimensional numerical hemolysis approximation method, which is in the range 0.006 ~ 0.094 g/100L. The results show that the pressure loss of the wearable oxygenator mainly occurs in the fiber bundle area. The inlet, outlet, and channels have relatively high shear stress, which may damage the red blood cells. When the flow rate ranges from 2.0 L/min to 5.0 L/min, the estimated hemolysis meets the applicable range allowed by human physiology. In addition, the parallel performance is studied on a supercomputer, which shows that, for the simulation with over 9 million mesh cells, it scales up to 720 processors and the parallel efficiency is over 60%.

Hemodynamic Characteristics of Cardiovascular System in Simulated Zero and Partial Gravities Based on CFD Modeling and Simulation.

Zero and partial gravities (ZPG) increase cardiovascular risk, while the corresponding theoretical foundation remains uncertain. In the article, the ZPG were generated through a rotating frame with two degrees of freedom in combination with the random walk algorithm. A precise 3D geometric configuration of the cardiovascular system was developed, and the Navier-Stokes laminar flow and solid mechanics were used as governing equations for blood flow and the surrounding tissue in the cardiovascular system. The ZPG were designed into governing equations through the volume force term. The computational fluid dynamics' (CFD) simulations in combination with proper boundary conditions were carried out to investigate the influences of ZPG on the distribution of blood flow velocity, pressure, and shear stress in the cardiovascular system. The findings show that as simulated gravity gradually decreases from 0.7 g to 0.5 g to 0.3 g to 0 g, as opposed to normal gravity of 1 g, the maximum values of blood flow velocity, pressure, and shear stress on the walls of the aorta and its ramification significantly increase, which would lead to cardiovascular diseases. The research will lay a theoretical foundation for the comprehension of the ZPG effect on cardiovascular risk and the development of effective prevention and control measures under the circumstance of ZPG.

Changes in miRNA expression in patients with peripheral arterial vascular disease during moderate- and vigorous-intensity physical activity

BackgroundWalking is the preferred therapy for peripheral arterial disease in early stage. An effect of walking exercise is the increase of blood flow and fluid shear stress, leading, triggered by arteriogenesis, to the formation of collateral blood vessels. Circulating micro-RNA may act as an important information transmitter in this process. We investigated the acute effects of a single bout of 1) aerobic walking with moderate intensity; and 2) anaerobic walking with vigorous intensity on miRNA parameters related to vascular collateral formation.MethodsTen (10) patients with peripheral arterial disease with claudication (age 72 ± 7 years) participated in this two-armed, randomized-balanced cross-over study. The intervention arms were single bouts of supervised walking training at (1) vigorous intensity on a treadmill up to volitional exhaustion and (2) moderate intensity with individual selected speed for a duration of 20 min. One week of washout was maintained between the arms. During each intervention, heart rate was continuously monitored. Acute effects on circulating miRNAs and lactate concentration were determined using pre- and post-intervention measurement comparisons.ResultsVigorous-intensity walking resulted in a higher heart rate (125 ± 21 bpm) than the moderate-intensity intervention (88 ± 9 bpm) (p < 0.05). Lactate concentration was increased after vigorous-intensity walking (p = 0.005; 3.3 ± 1.2 mmol/l), but not after moderate exercising (p > 0.05; 1.7 ± 0.6 mmol/l). The circulating levels of miR-142-5p and miR-424-5p were up-regulated after moderate-intensity (p < 0.05), but not after vigorous-intensity training (p > 0.05).ConclusionModerate-intensity walking seems to be more feasible than vigorous exercises to induce changes of blood flow and endurance training-related miRNAs in patients with peripheral arterial disease. Our data thus indicates that effect mechanisms might follow an optimal rather than a maximal dose response relation. Steady state walking without the necessity to reach exhaustion seems to be better suited as stimulus.

Low shear stress inhibits endothelial mitophagy via caveolin-1/miR-7-5p/SQSTM1 signaling pathway

Background and aimsMitophagy plays a crucial role in mitochondrial homeostasis and is closely associated with endothelial function. However, the mechanism underlying low blood flow shear stress (SS), detrimental cellular stress, regulating endothelial mitophagy is unclear. This study aimed to investigate whether low SS inhibits endothelial mitophagy via caveolin-1 (Cav-1)/miR-7-5p/Sequestosome 1 (SQSTM1) signaling pathway. MethodsLow SS in vivo modeling was induced using a perivascular SS modifier implanted in the carotid artery of mice. In vitro modeling, low and physiological SS (4 and 15 dyn/cm2, respectively) were exerted on human aortic endothelial cells using a parallel plate chamber system. ResultsCompared with physiological SS, low SS significantly inhibited endothelial mitophagy shown by down-regulation of SQSTM1, PINK1, Parkin, and LC 3II expressions. Deficient mitophagy deteriorated mitochondrial dynamics shown by up-regulation of Mfn1 and Fis1 expression and led to decreases in mitochondrial membrane potential. Cav-1 plays a bridging role in the process of low SS inhibiting mitophagy. The up-regulated miR-7-5p expression induced by low SS was suppressed after Cav-1 was silenced. The results of dual-luciferase reporter assays showed that miR-7-5p targeted inhibiting the SQSTM1 gene. Oxidative stress reaction shown by the elevation of reactive oxygen species and O2●— and endothelial dysfunction by the decrease in nitric oxide and the increase in macrophage chemoattractant protein-1 were associated with the low SS inhibiting endothelial mitophagy process. ConclusionsCav-1/miR-7-5p/SQSTM1 signaling pathway was the mechanism underlying low SS inhibiting endothelial mitophagy that involves mitochondrial homeostasis impairment and endothelial dysfunction.

To Explore the Effect of Preoperative Hemodynamic Factors on The Outcome of Pseudolumen After Stanford Type B Aortic Dissection TEVAR Based on Computer Fluid Dynamics.

The preoperative aortic hemodynamic data of patients with Stanford type B aortic dissection were obtained by computer fluid dynamics (CFD). Then we explored the relationship between hemodynamic data and short-term residual pseudolumen after thoracic endovascular aortic repair (TEVAR) and predict the latter through the former. We collected the relevant data of 53 patients who underwent TEVAR in our hospital. They were divided into the A group (residual false lumen group) and B group (closed false lumen group), according to whether there was a residual false cavity around the stent recently after TEVAR. Three-dimensional reconstruction and CFD analysis of the thoracic and abdominal aorta was performed by DSCTA before the operation to obtain the aortic wall shear stress (WSS) and maximum blood flow velocity of the true and false lumen at the entrance, middle point of the long axis, and distal decompression port at the peak time of ventricular systolic velocity. Through the statistical analysis, we further studied the predictive value of hemodynamic data for residual pseudolumen. There was no significant difference in age, male, preoperative and postoperative thoracic and abdominal aorta DSCTA interval, history of hypertension, history of diabetes, smoking, Pt and APTT at admission between the two groups (P > 0.05). The blood flow velocity and shear stress at the entrance of the false lumen and the distal decompression port in the two groups were statistically significant (P < 0.05), while the other hemodynamic indexes were not statistically significant (P > 0.05). Binary logistic regression analysis further showed that the shear stress of the false lumen at the level of the distal decompression port (OR = 1.73, P = 0.01) was an independent risk factor for the residual false lumen around the stent in the early stage after TEVAR. The ROC curve analysis showed that the AUC area of the ROC curve corresponding to the shear stress of the false cavity at the level of the distal decompression port was 0.83, the best cross-sectional value was 9.49pa, and the sensitivity and specificity were 84.60% and 72.50%. The residual pseudolumen after TEVAR is related to the hemodynamic factors in the aorta before TEVAR. Preoperative hemodynamic data also have good predictive value. When the shear stress of the false lumen at the level of the distal decompression port is greater than 9.49pa, the probability of residual false lumen around the stent during the perioperative period significantly increases.

Inflow Angle Impacts Morphology, Hemodynamics, and Inflammation of Side-wall Intracranial Aneurysms.

Aneurysm inflow angle has been shown to be associated with hemodynamic changes by computational fluid dynamics. However, these studies were based on single aneurysm model and were limited to side-wall aneurysms. To investigate the association between inflow angle and morphology, hemodynamic, and inflammation of intracranial side-wall and bifurcation aneurysms. Prospective. A total of 62 patients (aged 58.34 ± 12.39, 44 female) with 59 unruptured side-wall aneurysms and 17 unruptured bifurcation aneurysms were included. A 3.0 T; 3D fast field echo sequence (TOF-MRA); free-breathing, 3D radio-frequency-spoiled, multi-shot turbo field echo sequence (4D-flow MRI); 3D black-blood T1-weighted volumetric turbo spin echo acquisition sequence (T1 -VISTA) ASSESSMENT: Two neuroradiologists assessed the inflow angle and size for intracranial aneurysms in 3D space with TOF-MRA images. The average and maximum inflow velocity (Vavg-IA , Vmax-IA ), blood flow (Flowavg-IA , Flowmax-IA ), and average wall shear stress (WSSavg-IA ) for aneurysms were assessed from 4D-flow MRI in regions of interest drawn by two neuroradiologists. The aneurysmal wall enhancement (AWE) grades between precontrast and postcontrast T1 -VISTA images were evaluated by three neuroradiologists. Kruskal-Wallis H test, χ2 test, Pearson's correlation coefficient, scatter plots and regression lines, multivariate logistic regression analysis (partial correlation r) were performed. A P < 0.05 was considered statistically significant. The WSSavg-IA (0.52 ± 0.34 vs. 0.27 ± 0.22) and AWE grades (1.38 ± 1.04 vs. 2.02 ± 0.68) between the two inflow angle subgroups of side-wall aneurysms were significantly different. The aneurysm size (rs =0.31), WSSavg-IA (rs =-0.45), and AWE grades (rs =0.45) were significantly correlated with inflow angle in side-wall aneurysms. While in bifurcation aneurysms, there were no significant associations between inflow angle and size (P=0.901), Vavg-IA (P=0.699), Vmax-IA (P=0.482), Flowavg-IA (P=0.550), Flowmax-IA (P=0.689), WSSavg-IA (P=0.573), and AWE grades (P=0.872). A larger aneurysm size, a lower WSS and a higher AWE grade were correlated with a larger inflow angle in side-wall aneurysms. 3 TECHNICAL EFFICACY: Stage 2.