Shear Stress and Atherosclerosis

Hemodynamic shear stress, the frictional force acting on vascular endothelial cells, is crucial for endothelial homeostasis under normal physiological conditions. When discussing blood flow effects on various forms of endothelial (dys)function, one considers two flow patterns: steady laminar flow and disturbed flow because endothelial cells respond differently to these flow types both in vivo and in vitro. Laminar flow which exerts steady laminar shear stress is atheroprotective while disturbed flow creates an atheroprone environment. Emerging evidence has provided new insights into the cellular mechanisms of flow-dependent regulation of vascular function that leads to cardiovascular events such as atherosclerosis, atherothrombosis, and myocardial infarction. In order to study effects of shear stress and different types of flow, various models have been used. In this review, we will summarize our current views on how disturbed flow-mediated signaling pathways are involved in the development of atherosclerosis.

• Publication year

  2014

• Venue

  Molecules and Cells

• Publication date

  2014-04-30

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.14348/molcells.2014.0078PMID 24781409PMCID 4086336
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Non-motile primary cilia as fluid shear stress mechanosensors.

  2013cited by this paper
• De-SUMOylation Enzyme of Sentrin/SUMO-Specific Protease 2 Regulates Disturbed Flow–Induced SUMOylation of ERK5 and p53 that Leads to Endothelial Dysfunction and Atherosclerosis

  2013influential reference
• A Crucial Role for p90RSK-Mediated Reduction of ERK5 Transcriptional Activity in Endothelial Dysfunction and Atherosclerosis

  2013cited by this paper
• Role of endothelial shear stress in stent restenosis and thrombosis: pathophysiologic mechanisms and implications for clinical translation.

  2012cited by this paper
• Lessons from the endothelial junctional mechanosensory complex

  2012cited by this paper
• Obesity and risk of vascular disease: importance of endothelium‐dependent vasoconstriction

  2012cited by this paper
• PKCζ mediates disturbed flow-induced endothelial apoptosis via p53 SUMOylation

  2011influential reference
• Endothelial Glycocalyx: Permeability Barrier and Mechanosensor

  2011cited by this paper
• Disturbed-flow-mediated vascular reactive oxygen species induce endothelial dysfunction.

  2011influential reference
• Mechanotransduction of shear in the endothelium: Basic studies and clinical implications

  2011cited by this paper
• MK2 SUMOylation regulates actin filament remodeling and subsequent migration in endothelial cells by inhibiting MK2 kinase and HSP27 phosphorylation.

  2011cited by this paper
• SUMO-specific protease 2 in Mdm2-mediated regulation of p53

  2011cited by this paper
• SENP1 participates in the dynamic regulation of Elk-1 SUMOylation

  2010cited by this paper
• Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis.

  2009cited by this paper
• Flow Activation of AMP-Activated Protein Kinase in Vascular Endothelium Leads to Krüppel-Like Factor 2 Expression

  2009cited by this paper
• SUMOylation and De-SUMOylation: Wrestling with Life's Processes*

  2009cited by this paper
• Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology

  2009influential reference
• Vascular mechanobiology: endothelial cell responses to fluid shear stress.

  2009cited by this paper
• Physiologic stress-mediated signaling in the endothelium.

  2008cited by this paper
• Mechanotransduction in an extracted cell model: Fyn drives stretch- and flow-elicited PECAM-1 phosphorylation

  2008cited by this paper
• Endothelial Cell PECAM-1 Promotes Atherosclerotic Lesions in Areas of Disturbed Flow in ApoE-Deficient Mice

  2008cited by this paper
• Site-Specific Effects of PECAM-1 on Atherosclerosis in LDL Receptor–Deficient Mice

  2008cited by this paper
• Extracellular Signal-Regulated Kinase 5 SUMOylation Antagonizes Shear Stress–Induced Antiinflammatory Response and Endothelial Nitric Oxide Synthase Expression in Endothelial Cells

  2008influential reference
• SUMO-Specific Protease 2 Is Essential for Modulating p53-Mdm2 in Development of Trophoblast Stem Cell Niches and Lineages

  2008cited by this paper
• Concepts in sumoylation: a decade on

  2007cited by this paper
• Flow Antagonizes TNF-&agr; Signaling in Endothelial Cells by Inhibiting Caspase-Dependent PKC&zgr; Processing

  2007cited by this paper
• Relative reduction of endothelial nitric-oxide synthase expression and transcription in atherosclerosis-prone regions of the mouse aorta and in an in vitro model of disturbed flow.

  2007cited by this paper
• Flow antagonizes TNF-alpha signaling in endothelial cells by inhibiting caspase-dependent PKC zeta processing.

  2007cited by this paper
• Endothelial actin cytoskeleton remodeling during mechanostimulation with fluid shear stress.

  2006cited by this paper
• ERK5 Activation Inhibits Inflammatory Responses via Peroxisome Proliferator-activated Receptor δ (PPARδ) Stimulation*

  2006cited by this paper
• ERK5 activation inhibits inflammatory responses via peroxisome proliferator-activated receptor delta (PPARdelta) stimulation.

  2006cited by this paper
• Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis

  2006cited by this paper
• Direct evidence for the role of caveolin-1 and caveolae in mechanotransduction and remodeling of blood vessels.

  2006cited by this paper
• Role of PECAM-1 in the shear-stress-induced activation of Akt and the endothelial nitric oxide synthase (eNOS) in endothelial cells

  2005cited by this paper
• Gab1, SHP2, and Protein Kinase A Are Crucial for the Activation of the Endothelial NO Synthase by Fluid Shear Stress

  2005cited by this paper
• A mechanosensory complex that mediates the endothelial cell response to fluid shear stress

  2005cited by this paper
• The hinge-helix 1 region of peroxisome proliferator-activated receptor gamma1 (PPARgamma1) mediates interaction with extracellular signal-regulated kinase 5 and PPARgamma1 transcriptional activation: involvement in flow-induced PPARgamma activation in endothelial cells.

  2004cited by this paper
• Endothelial cell-cell adhesion and mechanosignal transduction.

  2004cited by this paper
• The Hinge-Helix 1 Region of Peroxisome Proliferator-Activated Receptor γ1 (PPARγ1) Mediates Interaction with Extracellular Signal-Regulated Kinase 5 and PPARγ1 Transcriptional Activation: Involvement in Flow-Induced PPARγ Activation in Endothelial Cells

  2004cited by this paper
• Big Mitogen-Activated Protein Kinase (BMK1)/ERK5 Protects Endothelial Cells From Apoptosis

  2004cited by this paper
• SENP1 Enhances Androgen Receptor-Dependent Transcription through Desumoylation of Histone Deacetylase 1

  2004cited by this paper
• Rapid activation of Ras by fluid flow is mediated by Galpha(q) and Gbetagamma subunits of heterotrimeric G proteins in human endothelial cells.

  2003cited by this paper
• Endothelial cell functions

  2003cited by this paper
• Rapid Activation of Ras by Fluid Flow Is Mediated by G&agr;q and G&bgr;&ggr; Subunits of Heterotrimeric G Proteins in Human Endothelial Cells

  2003cited by this paper
• Shear stress stimulates phosphorylation of eNOS at Ser(635) by a protein kinase A-dependent mechanism.

  2002cited by this paper
• Shear Stress Activation of SREBP1 in Endothelial Cells Is Mediated by Integrins

  2002cited by this paper
• Atheroprotective Mechanisms Activated by Fluid Shear Stress in Endothelial Cells.

  2002cited by this paper
• Integrin-mediated mechanotransduction requires its dynamic interaction with specific extracellular matrix (ECM) ligands.

  2001cited by this paper
• Activation of integrins in endothelial cells by fluid shear stress mediates Rho‐dependent cytoskeletal alignment

  2001cited by this paper
• Downloaded from http://circres.ahajournals.org / by guest on February 23, 2013Shear Stress Regulates Endothelial Nitric Oxide Synthase Expression Through c-Src by Divergent Signaling Pathways

  2001cited by this paper
• Rapid displacement of vimentin intermediate filaments in living endothelial cells exposed to flow.

  2000cited by this paper
• Lateral zone of cell-cell adhesion as the major fluid shear stress-related signal transduction site.

  2000cited by this paper
• The NF-kappa B signal transduction pathway in aortic endothelial cells is primed for activation in regions predisposed to atherosclerotic lesion formation.

  2000influential reference
• Responsiveness of vascular endothelium to shear stress: potential role of ion channels and cellular cytoskeleton (review).

  1999cited by this paper
• Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation.

  1999cited by this paper
• Laminar shear stress: mechanisms by which endothelial cells transduce an atheroprotective force.

  1998cited by this paper
• Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) in mechanically stimulated vascular endothelial cells.

  1997influential reference
• The expression of the adhesion molecules ICAM‐1, VCAM‐1, PECAM, and E‐selectin in human atherosclerosis

  1993cited by this paper
• Endothelium and Regulation of Coagulation

  1991cited by this paper
• Endothelium and regulation of coagulation.

  1991cited by this paper
• following articles: Role of Integrins in Endothelial Mechanosensing of Shear Stress Dance Band on the Titanic: Biomechanical Signaling in Cardiac Hypertrophy Spatial Microstimuli in Endothelial Mechanosignaling Dynamic Regulation of Connexins in Connectio

  year unknowncited by this paper

• Flow-dependent NRF2 dysfunction via KEAP1/WDR23 dual repression contributes to endothelial oxidative damage in venous disease.

  2026cites this paper
• Association of Ramus intermedius with increased atherosclerotic plaque in the left main stem.

  2026cites this paper
• FBXO38 Regulates Nox1 Stability to Reduce Vascular Endothelial Damage Induced by Low Oscillatory Shear Stress

  2025cites this paper
• The Role of 4D Flow MRI-derived Wall Shear Stress in Aortic Disease: A Comprehensive Review

  2025cites this paper
• Anti-atherosclerotic effect of aged garlic extract: Mode of action and therapeutic benefits (Review)

  2025cites this paper
• Exploring the mechanism of Xiaohuoluo Pill in the treatment of ischemic stroke based on GEO dataset combined with network pharmacology and molecular docking technology

  2025cites this paper
• Network pharmacology and UPLC/MS/MS metabolic profiling unveil the anti-inflammatory potential of Trifolium alexandrinum

  2025cites this paper
• TRPV4 Dominates High Shear-Induced Initial Traction Response and Long-Term Relaxation Over Piezo1

  2025cites this paper
• External-Force-Offset Effects of ECM Coating Layers on hMSCs Subjected to External Physical Force

  2025cites this paper
• High Shear Stress‐Induced Endothelial Piezo1 Downregulation Promotes Intracranial Aneurysm Formation via the PDGF‐BB/PDGFRβ Paracrine Signaling Pathway

  2025cites this paper
• Enhanced physics-informed generative adversarial network to estimate spatial-temporal distribution of shear stress in carotid arteries

  2025cites this paper
• H3K27Me3 abundance is associated with a decreased barrier function of endothelial cells by directly silencing VE-cadherin expression.

  2025cites this paper
• Mechanosensitive membrane domains regulate calcium entry in arterial endothelial cells to protect against inflammation

  2024cites this paper
• The roles of Hippo/YAP signaling pathway in physical therapy

  2024cites this paper
• Remodeling of the brain angioarchitecture in experimental chronic neurodegeneration

  2024cites this paper
• Ink-structing the future of vascular tissue engineering: a review of the physiological bioink design

  2024cites this paper
• Helical vasculogenesis driven by cell chirality

  2024cites this paper
• Shear Stress Induces a Time-Dependent Inflammatory Response in Human Monocyte-Derived Macrophages

  2024cites this paper
• Targeting extracellular matrix stiffness for cancer therapy

  2024cites this paper
• Heterogeneity of Endothelial Cells Impacts the Functionality of Human Pancreatic In Vitro Models

  2024cites this paper
• Patient-specific modelling of coronary hemodynamics: state of the art

  2024cites this paper
• Low or oscillatory shear stress and endothelial permeability in atherosclerosis

  2024cites this paper
• Syndecan 4 is a marker of endothelial inflammation in pathological aging and predicts long-term cardiovascular outcomes in type 2 diabetes

  2024cites this paper
• Modeling human atherosclerotic lesions in the test tube: Are we there yet?

  2024cites this paper
• The relationship of redox signaling with the risk for atherosclerosis

  2024cites this paper
• ECM Microenvironment in Vascular Homeostasis: New Targets for Atherosclerosis.

  2024cites this paper
• Cucurbitacins mitigate vascular neointimal hyperplasia by suppressing cyclin A2 expression and inhibiting VSMC proliferation

  2024cites this paper
• Applications, challenges, and prospects of induced pluripotent stem cells for vascular disease

  2024cites this paper
• Polarized Mechanosensitive Signaling Domains Protect Arterial Endothelial Cells Against Inflammation

  2023cites this paper
• A promising protocol for the endothelialization of vascular grafts in an instrumented rotating bioreactor towards clinical application

  2023cites this paper
• Vascular Inflammatory Diseases and Endothelial Phenotypes

  2023cites this paper
• The Interplay between Atherosclerosis and Cancer: Breast Cancer Cells Increase the Expression of Endothelial Cell Adhesion Markers

  2023cites this paper
• Possible molecular mechanisms underlying the development of atherosclerosis in cancer survivors

  2023cites this paper
• Anti-inflammation Nanomedicine Shots through Atherosclerotic Plaques for Targeted Treatment and Precise Diagnosis

  2023cites this paper
• An Oscillatory Shear Index-Based Model to Describe Progressive Carotid Artery Stenosis

  2022cites this paper
• Fluid Shear Stress Regulates the Landscape of microRNAs in Endothelial Cell-Derived Small Extracellular Vesicles and Modulates the Function of Endothelial Cells

  2022cites this paper
• Endothelial microparticles: A mechanosensitive regulator of vascular homeostasis and injury under shear stress

  2022cites this paper
• Angular difference in human coronary artery governs endothelial cell structure and function

  2022cites this paper
• NIR ‐triggered hydrogel with dynamic stiffness via ion chelation to modulate macrophage phenotypes

  2022cites this paper
• Detrimental effects of physical inactivity on peripheral and brain vasculature in humans: Insights into mechanisms, long-term health consequences and protective strategies

  2022cites this paper
• Atherogenesis, Transcytosis, and the Transmural Cholesterol Flux: A Critical Review

  2022cites this paper
• Spatiotemporal changes of local hemodynamics and plaque components during atherosclerotic progression in rabbit

  2022cites this paper
• Progerin-Induced Impairment in Wound Healing and Proliferation in Vascular Endothelial Cells

  2022cites this paper
• Nanohydroxyapatite-Blasted Bioactive Surface Drives Shear-Stressed Endothelial Cell Growth and Angiogenesis

  2022cites this paper
• Dendrobium catenatum Lindl. Water Extracts Attenuate Atherosclerosis

  2021cites this paper
• LXN deficiency regulates cytoskeleton remodelling by promoting proteolytic cleavage of Filamin A in vascular endothelial cells

  2021cites this paper
• Recent Developments in Nanomaterial‐Based Shear‐Sensitive Drug Delivery Systems

  2021cites this paper
• miR‐25‐5p regulates endothelial progenitor cell differentiation in response to shear stress through targeting ABCA1

  2021cites this paper
• Mechanotransduction-on-chip: vessel-chip model of endothelial YAP mechanobiology reveals matrix stiffness impedes shear response.

  2021cites this paper
• Rosuvastatin Inhibits the Apoptosis of Platelet-Derived Growth Factor–Stimulated Vascular Smooth Muscle Cells by Inhibiting p38 via Autophagy

  2021cites this paper
• Dilation-Responsive Microshape Programing Prevents Vascular Graft Stenosis.

  2021cites this paper
• The quiescent endothelium: signalling pathways regulating organ-specific endothelial normalcy

  2021cites this paper
• Single cell transcriptomic analysis identifies novel vascular smooth muscle subsets under high hydrostatic pressure

  2021cites this paper
• The role of connexin proteins and their channels in radiation-induced atherosclerosis

  2021cites this paper
• Plasma miRNAs improve the prediction of coronary atherosclerosis in patients with rheumatoid arthritis

  2021cites this paper
• Functional lipidomics of vascular endothelial cells in response to laminar shear stress

  2021cites this paper
• MÉTODO AUTOMÁTICO PARA LA MEDIDA DE LA VELOCIDAD DE FLUJO DE HEMOSUSTITUTOS EN ARTERIOLAS MEDIANTE PROCESAMIENTO DE IMÁGENES

  2021cites this paper
• From endothelial dysfunction to complicated atherosclerotic plaque -the long journey of the more lethal disease of our times-

  2021cites this paper
• Predicting the onset of consequent stenotic regions in carotid arteries using computational fluid dynamics

  2021cites this paper
• Ateroesclerosis

  2021cites this paper
• Oridonin attenuates low shear stress-induced endothelial cell dysfunction and oxidative stress by activating the nuclear factor erythroid 2-related factor 2 pathway

  2021cites this paper
• Relationship Between Coronary Atheroma, Epicardial Adipose Tissue Inflammation, and Adipocyte Differentiation Across the Human Myocardial Bridge

  2021cites this paper
• Novel Biomarkers of Endothelial Dysfunction in Cardiovascular Diseases

  2021cites this paper
• De la disfunción endotelial a la placa aterosclerótica complicada -el largo viaje de la enfermedad más letal de nuestro tiempo-

  2021cites this paper
• Establishment of an in vitro thrombogenicity test system with cyclic olefin copolymer substrate for endothelial layer formation

  2021cites this paper
• Endothelial Function in Patients With Continuous-Flow Left Ventricular Assist Devices

  2020cites this paper
• Biglycan and atherosclerosis: Lessons from high cardiovascular risk conditions.

  2020cites this paper
• Laminar flow inhibits the Hippo/YAP pathway via autophagy and SIRT1-mediated deacetylation against atherosclerosis

  2020cites this paper
• Geometric and hemodynamic analysis of fenestrated and multibranched aortic endografts.

  2020cites this paper
• ShearFAST: a user-friendly in vitro toolset for high throughput, inexpensive fluid shear stress experiments

  2020cites this paper
• Shear Stress in Schlemm’s Canal as a Sensor of Intraocular Pressure

  2020cites this paper
• A Study of Coronary Artery Disease in the Left Circumflex Artery via Artificial Vessel Restoration

  2020cites this paper
• Reconstructing haemodynamics quantities of interest from Doppler ultrasound imaging

  2020cites this paper
• The effect of bay leaf extract (Syzygium polyanthum) on vascular endothelial growth factor (VEGF) and CD31 (PECAM-1) expression in acute coronary syndrome.

  2020cites this paper
• Protective Activities of Dendrobium huoshanense C. Z. Tang et S. J. Cheng Polysaccharide against High-Cholesterol Diet-Induced Atherosclerosis in Zebrafish

  2020cites this paper
• Harnessing Mechanosensation in Next Generation Cardiovascular Tissue Engineering

  2020cites this paper
• Cell membrane rupture: a novel test reveals significant variations among different brands of tissue culture flasks

  2020cites this paper
• Combined ARFI Variance of Acceleration (VoA), Vector Flow, and Wall Shear Stress for Assessing Atherosclerotic Risk: Ex-Vivo Human Cadaveric Results

  2020cites this paper
• A pre-conditioning protocol of peripheral blood derived endothelial colony forming cells for endothelialization of tissue engineered constructs.

  2020cites this paper
• An unexpected paradox: wall shear stress in the aorta is less in patients with severe atherosclerosis regardless of obesity.

  2020cites this paper
• Endothelial Rap1 (Ras-Association Proximate 1) Restricts Inflammatory Signaling to Protect From the Progression of Atherosclerosis.

  2020cites this paper
• Нарушение целостности эндотелиального монослоя биопротезов клапанов сердца как триггер развития первичной тканевой несостоятельности

  2020cites this paper
• Measuring wall shear stress distribution in the carotid artery in an African population: Computational fluid dynamics versus ultrasound doppler velocimetry.

  2020cites this paper
• Features of local hemodynamics and the formation of atherosclerotic lesions in coronary artery bifurcation

  2020cites this paper
• Endothelial monolayer disruption in bioprosthetic heart valve as a trigger of primary tissue failure

  2020cites this paper
• Deciphering the Molecular Role of Non-coding RNA in Malignant Cardiac Disease

  2020cites this paper
• Endothelial monolayer disruption in bioprosthetic heart valve as a trigger of primary tissue failure

  2020cites this paper
• BOISE STATE UNIVERSITY GRADUATE COLLEGE DEFENSE COMMITTEE AND FINAL READING APPROVALS

  2019cites this paper
• Pumpless microfluidic devices for generating healthy and diseased endothelia.

  2019cites this paper
• Hypoxia as a Factor Involved in the Regulation of the apoA-1, ABCA1, and Complement C3 Gene Expression in Human Macrophages

  2019cites this paper
• Isolation, culturing and gene expression profiling of inner mass cells from stable and vulnerable carotid atherosclerotic plaques

  2019cites this paper
• Feeling the force : role of AmotL2 in normal development and cancer

  2019cites this paper
• Therapeutic targets for endothelial dysfunction in vascular diseases

  2019cites this paper
• Wortmannin targeting phosphatidylinositol 3‐kinase suppresses angiogenic factors in shear‐stressed endothelial cells

  2019cites this paper
• Evaluation of tomographic 3D ultrasound in vascular disease

  2019cites this paper
• Analysis of Flow and Wall Deformation in a Stenotic Flexible Channel Containing a Soft Core, Simulating Atherosclerotic Arteries

  2019cites this paper
• Cardiovascular disease models: A game changing paradigm in drug discovery and screening.

  2019cites this paper
• Therapeutic targets and drugs for hyper-proliferation of vascular smooth muscle cells

  2019cites this paper
• Analysis of Flow and Wall Deformation in a Stenotic Flexible Channel Containing a Soft Core, Simulating Atherosclerotic Arteries

  2019cites this paper
• Pathogenesis regarding development and structure of unstable atherosclerotic plaque in internal carotid artery in relation to high risk factors of an ischaemic stroke. Current status of knowledge

  2019cites this paper