scholarly journals Flow-mediated endothelial mechanotransduction

1995 ◽  
Vol 75 (3) ◽  
pp. 519-560 ◽  
Author(s):  
P. F. Davies
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Blood Vessel ◽  
Vascular Tone ◽  
Shear Stresses ◽  
Mechanical Forces ◽  
Hemodynamic Forces ◽  
Atherosclerotic Lesions ◽  
Arterial Structure ◽  
Gene Regulatory

Mechanical forces associated with blood flow play important roles in the acute control of vascular tone, the regulation of arterial structure and remodeling, and the localization of atherosclerotic lesions. Major regulation of the blood vessel responses occurs by the action of hemodynamic shear stresses on the endothelium. The transmission of hemodynamic forces throughout the endothelium and the mechanotransduction mechanisms that lead to biophysical, biochemical, and gene regulatory responses of endothelial cells to hemodynamic shear stresses are reviewed.

Numerical Analysis of Blood Flow in the Vertebral Artery

1982 ◽  
Vol 104 (2) ◽  
pp. 143-147 ◽  
Author(s):  
Takayoshi Fukushima ◽  
Takehiko Azuma ◽  
Teruo Matsuzawa
Keyword(s):  
Blood Flow ◽  
Numerical Analysis ◽  
Vertebral Artery ◽  
Arterial Blood Flow ◽  
Vascular Lesions ◽  
Shear Stresses ◽  
Hemodynamic Forces ◽  
Atherosclerotic Lesions ◽  
Arterial Blood ◽  
Structure Of Flow

Abnormal hemodynamic forces associated with distortions of blood vessel lumen have been thought to play an important role in the pathogenesis of focal vascular lesions. In the vertebral artery, segments located between osseous rings are ectatic compared with those surrounded by the rings. Based on the assumption that arterial blood flow was quasi-steady, this work was undertaken to investigate the structure of flow through arterial models with one or two sinusoidal stenoses. Numerical analysis was performed by an integral-momentum method. The validity of the method was examined by comparison of experimental data so far reported with theoretical results. Velocity and wall shear stress distributions were explored in a model with two stenoses simulating a part of the vertebral artery. The ectatic segments of the vertebral artery have been known as predilection sites for atherosclerotic lesions. The present study suggested that the ectatic wall was under unstable shear stresses, the direction of which was dependent upon the magnitude of the Reynolds number.

scholarly journals Piezo1 is a mechanosensor channel in CNS capillaries

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Osama F. Harraz ◽  
Nicholas R. Klug ◽  
Amanda Senatore ◽  
Masayo Koide ◽  
Mark T. Nelson
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Ex Vivo ◽  
Outer Wall ◽  
Channel Blockers ◽  
Control Mechanisms ◽  
Hemodynamic Forces ◽  
Capillary Endothelial Cells ◽  
Patch Clamp Electrophysiology ◽  
And Function

Cerebral blood flow (CBF) is exquisitely controlled to meet the ever-changing demands of active neurons in the brain. Brain capillaries are equipped with sensors of neurovascular coupling agents released from neurons/astrocytes onto the outer wall of a capillary. While capillaries can translate external signals into electrical and Ca2+ changes, control mechanisms from the lumen are less clear. The continuous flux of red blood cells and plasma through narrow-diameter capillaries imposes mechanical forces on the luminal (inner) capillary wall. Whether—and, if so, how—the ever-changing CBF could be mechanically sensed in capillaries is not known. Here, we propose and provide evidence that the mechanosensitive Piezo1 channels operate as mechanosensors in CNS capillaries to ultimately regulate CBF. Patch clamp electrophysiology confirmed the expression and function of Piezo1 channels in brain cortical and retinal capillary endothelial cells. Mechanical or pharmacological activation of Piezo1 channels evoked currents that were sensitive to Piezo1 channel blockers. Using genetically encoded Ca2+ indicator (Cdh5-GCaMP8) mice, we observed that Piezo1 channel activation triggered Ca2+ signals in endothelial cells. An ex vivo pressurized retina preparation was employed to further explore the mechanosensitivity of capillary Piezo1-mediated Ca2+ signals. Genetic and pharmacologic manipulation of Piezo1 in endothelial cells had significant impacts on CBF, reemphasizing the crucial role of mechanosensation in blood flow control. In conclusion, this study shows that Piezo1 channels act as mechanosensors in capillaries, and that these channels initiate crucial Ca2+ signals. We further show that Piezo1 modulates CBF, an observation of profound significance for the control of brain blood flow in health and in disorders where hemodynamic forces are disrupted, such as hypertension.

scholarly journals Mechanoregulation of Vascular Endothelial Growth Factor Receptor 2 in Angiogenesis

2022 ◽  
Vol 8 ◽  
Author(s):  
Bronte Miller ◽  
Mary Kathryn Sewell-Loftin
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Blood Vessel ◽  
Mechanical Forces ◽  
Vascular Endothelial ◽  
Vascular Growth ◽  
Disease States ◽  
Biomechanical Forces ◽  
Endothelial Growth Factor

The endothelial cells that compose the vascular system in the body display a wide range of mechanotransductive behaviors and responses to biomechanical stimuli, which act in concert to control overall blood vessel structure and function. Such mechanosensitive activities allow blood vessels to constrict, dilate, grow, or remodel as needed during development as well as normal physiological functions, and the same processes can be dysregulated in various disease states. Mechanotransduction represents cellular responses to mechanical forces, translating such factors into chemical or electrical signals which alter the activation of various cell signaling pathways. Understanding how biomechanical forces drive vascular growth in healthy and diseased tissues could create new therapeutic strategies that would either enhance or halt these processes to assist with treatments of different diseases. In the cardiovascular system, new blood vessel formation from preexisting vasculature, in a process known as angiogenesis, is driven by vascular endothelial growth factor (VEGF) binding to VEGF receptor 2 (VEGFR-2) which promotes blood vessel development. However, physical forces such as shear stress, matrix stiffness, and interstitial flow are also major drivers and effectors of angiogenesis, and new research suggests that mechanical forces may regulate VEGFR-2 phosphorylation. In fact, VEGFR-2 activation has been linked to known mechanobiological agents including ERK/MAPK, c-Src, Rho/ROCK, and YAP/TAZ. In vascular disease states, endothelial cells can be subjected to altered mechanical stimuli which affect the pathways that control angiogenesis. Both normalizing and arresting angiogenesis associated with tumor growth have been strategies for anti-cancer treatments. In the field of regenerative medicine, harnessing biomechanical regulation of angiogenesis could enhance vascularization strategies for treating a variety of cardiovascular diseases, including ischemia or permit development of novel tissue engineering scaffolds. This review will focus on the impact of VEGFR-2 mechanosignaling in endothelial cells (ECs) and its interaction with other mechanotransductive pathways, as well as presenting a discussion on the relationship between VEGFR-2 activation and biomechanical forces in the extracellular matrix (ECM) that can help treat diseases with dysfunctional vascular growth.

Effects of Disturbed Flow On Endothelial Cells

1998 ◽  
Vol 120 (1) ◽  
pp. 2-8 ◽  
Author(s):  
J.-J. Chiu ◽  
D. L. Wang ◽  
S. Chien ◽  
R. Skalak ◽  
S. Usami
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Flow Direction ◽  
Arterial System ◽  
Shear Stresses ◽  
Stress Distributions ◽  
Complex Flow ◽  
Local Flow ◽  
Atherosclerotic Lesions

Atherosclerotic lesions tend to localize at curvatures and branches of the arterial system, where the local flow is often disturbed and irregular (e.g., flow separation, recirculation, complex flow patterns, and nonuniform shear stress distributions). The effects of such flow conditions on cultured human umbilical vein endothelial cells (HUVECs) were studied in vitro by using a vertical-step flow channel (VSF). Detailed shear stress distributions and flow structures have been computed by using the finite volume method in a general curvilinear coordinate system. HUVECs in the reattachment areas with low shear stresses were generally rounded in shape. In contrast, the cells under higher shear stresses were significantly elongated and aligned with the flow direction, even for those in the area with reversed flow. When HUVECs were subjected to shearing in VSF, their actin stress fibers reorganized in association with the morphological changes. The rate of DNA synthesis in the vicinity of the flow reattachment area was higher than that in the laminar flow area. These in vitro experiments have provided data for the understanding of the in vivo responses of endothelial cells under complex flow environments found in regions of prevalence of atherosclerotic lesions.

How Do Vascular Endothelial Cells Respond to Flow?

Physiology ◽  
1989 ◽  
Vol 4 (1) ◽  
pp. 22-25 ◽  
Author(s):  
PF Davies
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Shear Stresses ◽  
Vascular Endothelial ◽  
Small Arteries ◽  
Large Arteries ◽  
Hemodynamic Forces

Endothelial cells lining the circulation are continuously subjected to hemodynamic forces. Because flow is known to influence constriction and relaxation of small arteries and is implicated in the localization of athherosclerotic lesions in large arteries, the role of the endothelium as a "mechanotransducer" of flow-related forces, particularly shear stresses, is of great interest.

Regulation of vascular tone

1995 ◽  
Vol 73 (5) ◽  
pp. 544-550 ◽  
Author(s):  
Sandro Rossitti ◽  
John Frangos ◽  
Peggy R. Girard ◽  
John Bevan
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Shear Stress ◽  
Blood Vessel ◽  
Vascular Tone ◽  
Vascular System ◽  
Tangential Force ◽  
Relative Size ◽  
Matrix Shear

The intimal surface of the blood vessel in vivo is subject to shear stress resulting from blood flow, which in most of the circulation, at least at rest, is laminar. Turbulence can occur at bifurcations, especially those of the large arteries, and where vessels curve significantly. Shear stress is a frictional tangential force exerted at the fluid–intimal interface in the long axis of the vessel. It is now known that hemodynamic shear stress can influence a large variety of biological processes in endothelial cells, which vary from those with a short response time, just a few milliseconds, such as the opening of ion channels, to those that change over a period of minutes to several hours, for example, endocytosis and cytoskeleton rearrangement, and those features that alter much more slowly, such as cell shape and stiffness. In addition to these types of changes, there are suggestions that flow acting through shear stress may be responsible for several basic attributes of the vasculature, including the relative size and diameter of the components of a branching vascular system. In this symposium on the flow regulation of the blood vessel, the first presentation dealt with optimality principles that appear to govern the dimensions of the vasculature, in particular the geometry of the arterial branching and the role of shear stress. An optimally designed system is one that requires the least metabolic work to perform its function. The subsequent three presentations focussed on the effect of shear stress on three different aspects of the artery wall, the composition and organization of the extracellular matrix, the production of vasoactive factors by the endothelium, and the regulation of vascular tone.Key words: endothelial cells, extracellular matrix, shear stress, vascular smooth muscle, vascular tone.

scholarly journals Weibel Palade Bodies: Unique Secretory Organelles of Endothelial Cells that Control Blood Vessel Homeostasis

2021 ◽  
Vol 9 ◽  
Author(s):  
Johannes Naß ◽  
Julian Terglane ◽  
Volker Gerke
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Plasma Membrane ◽  
Blood Vessel ◽  
Blood Cells ◽  
Secretory Granules ◽  
Von Willebrand Disease ◽  
Rab Proteins ◽  
Membrane Tethering ◽  
Von Willebrand

Vascular endothelial cells produce and release compounds regulating vascular tone, blood vessel growth and differentiation, plasma composition, coagulation and fibrinolysis, and also engage in interactions with blood cells thereby controlling hemostasis and acute inflammatory reactions. These interactions have to be tightly regulated to guarantee smooth blood flow in normal physiology, but also allow specific and often local responses to blood vessel injury and infectious or inflammatory insults. To cope with these challenges, endothelial cells have the remarkable capability of rapidly changing their surface properties from non-adhesive (supporting unrestricted blood flow) to adhesive (capturing circulating blood cells). This is brought about by the evoked secretion of major adhesion receptors for platelets (von-Willebrand factor, VWF) and leukocytes (P-selectin) which are stored in a ready-to-be-used form in specialized secretory granules, the Weibel-Palade bodies (WPB). WPB are unique, lysosome related organelles that form at the trans-Golgi network and further mature by receiving material from the endolysosomal system. Failure to produce correctly matured VWF and release it through regulated WPB exocytosis results in pathologies, most importantly von-Willebrand disease, the most common inherited blood clotting disorder. The biogenesis of WPB, their intracellular motility and their fusion with the plasma membrane are regulated by a complex interplay of proteins and lipids, involving Rab proteins and their effectors, cytoskeletal components as well as membrane tethering and fusion machineries. This review will discuss aspects of WPB biogenesis, trafficking and exocytosis focussing on recent findings describing factors contributing to WPB maturation, WPB-actin interactions and WPB-plasma membrane tethering and fusion.

Velocity Measurement of In Vitro Blood Flow in Microchip Cultured Endothelial Cells

2008 ◽  
Author(s):  
Naoki Segawa ◽  
Yasuhiko Sugii
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Blood Vessel ◽  
Cell Attachment ◽  
Three Dimensional ◽  
Vascular Diseases ◽  
Culture Method ◽  
Measured Velocity ◽  
Micro Piv

In order to investigate vascular diseases such as cause of atherosclerosis and myocardial infarction, relationships of endothelial cells (ECs) covered with surface blood vessels and blood flow stimulation have been experimentally studied. In the study, a blood vessel model for in vitro experiment made from polydimethylsiloxane (PDMS) microchip with a straight microchannel with 400 μm width and 100 μm depth was developed. By optimizing cells cultured condition such as the liquid introduction method and the surface coating for enhancement of cell attachment on the microchannel wall, cell culture method in the microchip were developed. Velocity distributions on the ECs surface in the blood vessel model were measured using micro PIV technique. Measured velocity vectors on the ECs surface were fluctuated caused by the three dimensional effect of the cell shape.

scholarly journals Numerical Investigation of the Fetal Left Heart Hemodynamics During Gestational Stages

2021 ◽  
Vol 12 ◽  
Author(s):  
Huseyin Enes Salman ◽  
Reema Yousef Kamal ◽  
Huseyin Cagatay Yalcin
Keyword(s):  
Blood Flow ◽  
Mitral Valve ◽  
Heart Defects ◽  
Shear Stresses ◽  
Ultrasound Images ◽  
Left Heart ◽  
Hemodynamic Forces ◽  
Hemodynamic Assessment ◽  
Peak Shear Stress ◽  
Gestational Week

Flow-driven hemodynamic forces on the cardiac tissues have critical importance, and have a significant role in the proper development of the heart. These mechanobiological mechanisms govern the cellular responses for the growth and remodeling of the heart, where the altered hemodynamic environment is believed to be a major factor that is leading to congenital heart defects (CHDs). In order to investigate the mechanobiological development of the normal and diseased hearts, identification of the blood flow patterns and wall shear stresses (WSS) on these tissues are required for an accurate hemodynamic assessment. In this study, we focus on the left heart hemodynamics of the human fetuses throughout the gestational stages. Computational fetal left heart models are created for the healthy fetuses using the ultrasound images at various gestational weeks. Realistic inflow boundary conditions are implemented in the models using the Doppler ultrasound measurements for resolving the specific blood flow waveforms in the mitral valve. Obtained results indicate that WSS and vorticity levels in the fetal left heart decrease with the development of the fetus. The maximum WSS around the mitral valve is determined around 36 Pa at the gestational week of 16. This maximum WSS decreases to 11 Pa at the gestational week of 27, indicating nearly three-times reduction in the peak shear stress. These findings reveal the highly dynamic nature of the left heart hemodynamics throughout the development of the human fetus and shed light into the relevance of hemodynamic environment and development of CHDs.

Experimental Investigation of the Local Blood Flow Pattern in Stented Coronary Bifurcations

2011 ◽  
Author(s):  
Stefano Morlacchi ◽  
Jaime Schmieg ◽  
Dan Cooper ◽  
Francesco Burzotta ◽  
Francesco Migliavacca ◽  
...  
Keyword(s):  
Blood Flow ◽  
Invasive Procedure ◽  
Cost Effective ◽  
Clinical Results ◽  
Shear Stresses ◽  
Local Blood Flow ◽  
Time Saving ◽  
Acute Thrombosis ◽  
Hemodynamic Forces ◽  
Stent Restenosis

Stenting procedures give the opportunity to treat cardiovascular diseases with a time saving, cost effective and minimally invasive procedure when compared to coronary artery by-pass, while ensuring improved clinical results than balloon angioplasty. However, despite their success, stenting procedures are still associated with some clinical problems like sub-acute thrombosis (ST) and in-stent restenosis (ISR). Several clinical studies associate these issues to the local blood flow alterations caused by stent implantation. In particular, hemodynamic forces like wall shear stresses induce endothelial cells to experience an enhanced proliferative attitude.

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