Adaptive responses of vascular wall to fluid shear stress induced by blood flow

1992 ◽  
Author(s):  
Akira Kamiya ◽  
Joji Ando ◽  
Mitra Sohirad
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Vascular Wall ◽  
Adaptive Responses ◽  
Fluid Shear

scholarly journals CD44 regulates blood-brain barrier integrity in response to fluid shear stress

2020 ◽  
Author(s):  
Brandon J. DeOre ◽  
Paul P. Partyka ◽  
Fan Fan ◽  
Peter A. Galie
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Blood Brain Barrier ◽  
Fluid Shear Stress ◽  
Small Gtpase ◽  
Brain Barrier ◽  
Fluid Shear ◽  
Blood Brain

AbstractFluid shear stress is an important mediator of vascular permeability, yet the molecular mechanisms underlying the response of the blood-brain barrier to shear have yet to be studied in cerebral vasculature despite its importance for brain homeostasis. The goal of this study is to probe components of shear mechanotransduction within the blood-brain barrier to gain a better understanding of pathologies associated with changes in cerebral blood flow including ischemic stroke. Interrogating the effects of shear stress in vivo is complicated by the complexity of factors in the brain parenchyma and the difficulty associated with modulating blood flow regimes. Recent advances in the ability to mimic the in vivo microenvironment using three-dimensional in vitro models provide a controlled setting to study the response of the blood-brain barrier to shear stress. The in vitro model used in this study is compatible with real-time measurement of barrier function using transendothelial electrical resistance as well as immunocytochemistry and dextran permeability assays. These experiments reveal that there is a threshold level of shear stress required for barrier formation and that the composition of the extracellular matrix, specifically the presence of hyaluronan, dictates the flow response. Gene editing to modulate the expression of CD44, a receptor for hyaluronan that previous studies have identified to be mechanosensitive, demonstrates that the receptor is required for the endothelial response to shear stress. Manipulation of small GTPase activity reveals CD44 activates Rac1 while inhibiting RhoA activation. Additionally, adducin-γ localizes to tight junctions in response to shear stress and RhoA inhibition and is required to maintain the barrier. This study identifies specific components of the mechanosensing complex associated with the blood-brain barrier response to fluid shear stress, and therefore illuminates potential targets for barrier manipulation in vivo.

Application of fluid shear stress to engineered vascular wall using microchannel

2019 ◽  
Vol 2019.10 (0) ◽  
pp. 20am2PN307
Author(s):  
Yuya Morimoto ◽  
Shogo Nagata ◽  
Ai Shima ◽  
Shigenori Miura ◽  
Shoji Takeuchi
Keyword(s):  
Shear Stress ◽  
Fluid Shear Stress ◽  
Vascular Wall ◽  
Fluid Shear

scholarly journals Heg1 and Ccm1/2 proteins control endocardial mechanosensitivity during zebrafish valvulogenesis

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Stefan Donat ◽  
Marta Lourenço ◽  
Alessio Paolini ◽  
Cécile Otten ◽  
Marc Renz ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Cavernous Malformation ◽  
Cardiac Valve ◽  
Valve Leaflet ◽  
Fluid Shear ◽  
Binding Partner ◽  
Different Levels

Endothelial cells respond to different levels of fluid shear stress through adaptations of their mechanosensitivity. Currently, we lack a good understanding of how this contributes to sculpting of the cardiovascular system. Cerebral cavernous malformation (CCM) is an inherited vascular disease that occurs when a second somatic mutation causes a loss of CCM1/KRIT1, CCM2, or CCM3 proteins. Here, we demonstrate that zebrafish Krit1 regulates the formation of cardiac valves. Expression of heg1, which encodes a binding partner of Krit1, is positively regulated by blood-flow. In turn, Heg1 stabilizes levels of Krit1 protein, and both Heg1 and Krit1 dampen expression levels of klf2a, a major mechanosensitive gene. Conversely, loss of Krit1 results in increased expression of klf2a and notch1b throughout the endocardium and prevents cardiac valve leaflet formation. Hence, the correct balance of blood-flow-dependent induction and Krit1 protein-mediated repression of klf2a and notch1b ultimately shapes cardiac valve leaflet morphology.

Negative regulation of vascular smooth muscle cell migration by blood shear stress

2007 ◽  
Vol 292 (2) ◽  
pp. H928-H938 ◽  
Author(s):  
Jeremy Goldman ◽  
Lin Zhong ◽  
Shu Q. Liu
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vein Graft ◽  
Fluid Shear Stress ◽  
Fluid Shear ◽  
Vein Grafts ◽  
Polymer Implant

Vortex blood flow with reduced blood shear stress in a vein graft has been hypothesized to promote smooth muscle cell (SMC) migration and intimal hyperplasia, pathological events leading to vein graft restenosis. To demonstrate that blood shear stress regulates these processes, we developed a modified vein graft model where the SMC response to reduced vortex blood flow was compared with that of control vein grafts. Vortex blood flow induced SMC migration and neointimal hyperplasia in control vein grafts, whereas reduction of vortex blood flow in the modified vein graft strongly suppressed these effects. A venous polymer implant with known fluid shear stress was employed to clarify the molecular mechanism of shear-dependent SMC migration in vivo. In the polymer implant, the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and myosin light chain kinase (MLCK), found primarily in SMCs, increased from day 3 to day 5 and returned toward the control level from day 5 to day 10, with the peak phosphorylation associated with the maximal speed of SMC migration. Treatment with PD-98059 (an inhibitor specific to the ERK1/2 activator MEK1/2) significantly suppressed the phosphorylation of MLCK, suggesting a role for ERK1/2 in regulating the activity of MLCK. Treatment with PD-98059 or ML-7 (an inhibitor specific to MLCK) reduced shear stress-dependent SMC migration, resulting in an SMC distribution independent of fluid shear stress. These results suggest that fluid shear stress regulates SMC migration via the mediation of ERK1/2 and MLCK.

scholarly journals Neutrophil mechanotransduction: A GEF to sense fluid shear stress

2016 ◽  
Vol 215 (1) ◽  
pp. 13-14 ◽  
Author(s):  
Philipp Niethammer
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Neutrophil Migration ◽  
Transendothelial Migration ◽  
Nucleotide Exchange ◽  
Fluid Shear ◽  
Flow Shear ◽  
Exchange Factor ◽  
Nucleotide Exchange Factor

Forces deriving from blood flow shear modulate vascular adherence and transendothelial migration of leukocytes into inflamed tissues, but the mechanisms by which shear is sensed are unclear. In this issue, Fine et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201603109) identify the guanosine nucleotide exchange factor GEF-H1 as critical for shear stress–induced transendothelial neutrophil migration.

scholarly journals A compliant tubular device to study the influences of wall strain and fluid shear stress on cells of the vascular wall

1994 ◽  
Vol 20 (2) ◽  
pp. 184-194 ◽  
Author(s):  
Aziz Benbrahim ◽  
Gilbert J. L'Italien ◽  
Barbara B. Milinazzo ◽  
David F. Warnock ◽  
Sandip Dhara ◽  
...  
Keyword(s):  
Shear Stress ◽  
Fluid Shear Stress ◽  
Vascular Wall ◽  
Fluid Shear

scholarly journals Go with the Flow—Trophoblasts in Flow Culture

2020 ◽  
Vol 21 (13) ◽  
pp. 4666
Author(s):  
Beatrice A. Brugger ◽  
Jacqueline Guettler ◽  
Martin Gauster
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Fluid Shear Stress ◽  
Placental Tissue ◽  
Cell Types ◽  
Maternal Blood ◽  
Experimental Setup ◽  
Low Oxygen ◽  
Fluid Shear ◽  
Endocrine Activity

With establishment of uteroplacental blood flow, the perfused fetal chorionic tissue has to deal with fluid shear stress that is produced by hemodynamic forces across different trophoblast subtypes. Amongst many other cell types, trophoblasts are able to sense fluid shear stress through mechanotransduction. Failure in the adaption of trophoblasts to fluid shear stress is suggested to contribute to pregnancy disorders. Thus, in the past twenty years, a significant body of work has been devoted to human- and animal-derived trophoblast culture under microfluidic conditions, using a rather broad range of different fluid shear stress values as well as various different flow systems, ranging from commercially 2D to customized 3D flow culture systems. The great variations in the experimental setup reflect the general heterogeneity in blood flow through different segments of the uteroplacental circulation. While fluid shear stress is moderate in invaded uterine spiral arteries, it drastically declines after entrance of the maternal blood into the wide cavity of the intervillous space. Here, we provide an overview of the increasing body of evidence that substantiates an important influence of maternal blood flow on several aspects of trophoblast physiology, including cellular turnover and differentiation, trophoblast metabolism, as well as endocrine activity, and motility. Future trends in trophoblast flow culture will incorporate the physiological low oxygen conditions in human placental tissue and pulsatile blood flow in the experimental setup. Investigation of trophoblast mechanotransduction and development of mechanosome modulators will be another intriguing future direction.

scholarly journals Increased Intravascular Flow Rate Triggers Cerebral Arteriogenesis

2009 ◽  
Vol 29 (4) ◽  
pp. 726-737 ◽  
Author(s):  
Wilma Schierling ◽  
Kerstin Troidl ◽  
Clemens Mueller ◽  
Christian Troidl ◽  
Hanna Wustrack ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Blood Flow ◽  
Shear Stress ◽  
Magnetic Resonance ◽  
Fluid Shear Stress ◽  
Mononuclear Cells ◽  
Resonance Imaging ◽  
Fluid Shear ◽  
Bilateral Carotid ◽  
Venous Fistula

Peripheral arteriogenesis is distinctly enhanced by increased fluid shear stress. Thus, the aim of this study was to investigate in the rat brain whether increased fluid shear stress can also stimulate cerebral arteriogenesis. To increase fluid shear stress in the cerebral circulation, we developed different shear stress models as the ligature of both common carotid arteries ( Double-Ligature model), bilateral carotid ligature followed by creation of a unilateral arterio-venous fistula (two-stage protocol, Ligature-Shunt model), and unilateral arterio-venous fistula-creation alone ( Solo-Shuntmodel). Blood flow changes were monitored in vivo by quantitative magnetic resonance imaging-analysis. Cerebral arteriogenesis was analyzed by magnetic resonance imaging and contrast agent-angiography. For proliferation and accumulation of mononuclear cells, immunohistochemistry was performed. During the 14 days-observation period, blood flow increased maximal by 5.5-fold in the A. basilaris and 10.3-fold in the fistula-sided A. cerebri posterior of the Ligature-Shunt model. Considerable vessel growth was found in all shear stress-stimulated arteries. Comparative analysis of vessel length and diameter versus blood flow indicated a correlation between the growth of cerebral collaterals and rising intravascular flow rates ( R2 = 0.90/0.96). Immunohistochemistry showed the typical phases of arteriogenesis and accumulation of mononuclear cells. In conclusion, we provide evidence that fluid shear stress is not only the pivotal trigger of peripheral but also of cerebral arteriogenesis.

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