I022 Role of heme oxygenase-1 in high blood flow (shear stress)-induced remodeling of rat resistance arteries

Resistance arteries are the site of the earliest manifestations of many cardiovascular and metabolic diseases. Flow (shear stress) is the main physiological stimulus for the endothelium through the activation of vasodilatory pathways generating flow-mediated dilation (FMD). The role of FMD in local blood flow control and angiogenesis is well established, and alterations in FMD are early markers of cardiovascular disorders. α1-Integrin, which has a role in angiogenesis, could be involved in FMD. FMD was studied in mesenteric resistance arteries (MRA) isolated in arteriographs. The role of α1-integrins in FMD was tested with selective antibodies and mice lacking the gene encoding for α1-integrins. Both anti-α1blocking antibodies and genetic deficiency in α1-integrin in mice (α1−/−) inhibited FMD without affecting receptor-mediated (acetylcholine) endothelium-dependent dilation or endothelium-independent dilation (sodium nitroprusside). Similarly, vasoconstrictor tone (myogenic tone and phenylephrine-induced contraction) was not affected. In MRA phosphorylated Akt and phosphatidylinositol 3-kinase (PI3-kinase) were significantly lower in α1−/−mice than in α1+/+mice, although total Akt and endothelial nitric oxide synthase (eNOS) were not affected. Pharmacological blockade of PI3-kinase-Akt pathway with LY-294002 inhibited FMD. This inhibitory effect of LY-294002 was significantly lower in α1−/−mice than in α1+/+mice. Thus α1-integrin has a key role in flow (shear stress)-dependent vasodilation in resistance arteries by transmitting the signal to eNOS through activation of PI3-kinase and Akt. Because of the central role of flow (shear stress) activation of the endothelium in vascular disorders, this finding opens new perspectives in the pathophysiology of the microcirculation and provides new therapeutic targets.

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Alteration in flow (shear stress)-induced remodelling in rat resistance arteries with aging: improvement by a treatment with hydralazine

Cardiovascular Research ◽

10.1093/cvr/cvm055 ◽

2007 ◽

Vol 77 (3) ◽

pp. 600-608 ◽

Cited By ~ 33

Author(s):

O. Dumont ◽

F. Pinaud ◽

A.-L. Guihot ◽

C. Baufreton ◽

L. Loufrani ◽

...

Keyword(s):

Shear Stress ◽

Resistance Arteries ◽

Flow Shear ◽

Flow Shear Stress

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A test of the role of flow-dependent dilation in arteriolar responses to occlusion

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.272.2.h714 ◽

1997 ◽

Vol 272 (2) ◽

pp. H714-H721 ◽

Cited By ~ 12

Author(s):

E. D. McGahren ◽

K. A. Dora ◽

D. N. Damon ◽

B. R. Duling

Keyword(s):

Shear Stress ◽

Baseline Level ◽

Cheek Pouch ◽

Hamster Cheek Pouch ◽

Flow Shear ◽

Flow Through ◽

Flow Shear Stress ◽

Arteriolar Diameter

At an arteriolar bifurcation, occlusion of one of the branch arterioles has been reported to result in an increase in flow, shear stress, and vasodilation in the opposite unoccluded branch. This dilator response in the unoccluded branch, often referred to as the "parallel occlusion response," has been cited as evidence that flow-dependent dilation is a primary regulator of arteriolar diameter in the microcirculation. It has not been previously noted that, during this maneuver, flow through the feed arteriole would be expected to decrease and logically should cause that vessel to constrict. We tested this prediction in vivo by measuring red blood cell (RBC) velocity and diameter changes in response to arteriolar occlusion in the microcirculatory beds of three preparations: the hamster cheek pouch, the hamster cremaster, and the rat cremaster. In all preparations, a vasodilation was observed in the feed arteriole, despite a decrease in both flow and calculated wall shear stress through this vessel. Unexpectedly, we found that dilation occurred in the unoccluded branch arterioles even in those cases in which RBC velocity and shear stress did not increase in the unoccluded branch arterioles. All values returned to the baseline level after the removal of occlusion. The magnitude of the dilation of the feed and branch arterioles varied between species and tissues, but feed and branch arterioles within a given preparation always responded in a similar way to each other. We conclude from our experiments that mechanisms other than flow-dependent dilation are involved in the vasodilation observed in the microcirculation during occlusion of an arteriolar branch.

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Reactive Oxygen Species Are Necessary for High Flow (Shear Stress)-induced Diameter Enlargement of Rat Resistance Arteries

Microcirculation ◽

10.1080/10739680902816301 ◽

2009 ◽

Vol 16 (5) ◽

pp. 391-402 ◽

Cited By ~ 30

Author(s):

Eric J. Belin De Chantemèle ◽

Emilie Vessières ◽

Odile Dumont ◽

Anne-Laure Guihot ◽

Bertrand Toutain ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Shear Stress ◽

Reactive Oxygen ◽

High Flow ◽

Oxygen Species ◽

Resistance Arteries ◽

Flow Shear ◽

Flow Shear Stress

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Tissue Engineered Tumor Microvessels to Study the Role of Flow Shear Stress on Endothelial Barrier Function

Volume 1B: Extremity; Fluid Mechanics; Gait; Growth, Remodeling, and Repair; Heart Valves; Injury Biomechanics; Mechanotransduction and Sub-Cellular Biophysics; MultiScale Biotransport; Muscle, Tendon and Ligament; Musculoskeletal Devices; Multiscale Mechanics; Thermal Medicine; Ocular Biomechanics; Pediatric Hemodynamics; Pericellular Phenomena; Tissue Mechanics; Biotransport Design and Devices; Spine; Stent Device Hemodynamics; Vascular Solid Mechanics; Student Paper and Design Competitions ◽

10.1115/sbc2013-14592 ◽

2013 ◽

Author(s):

Cara F. Buchanan ◽

Elizabeth Voigt ◽

Pavlos P. Vlachos ◽

Marissa Nichole Rylander

Keyword(s):

Shear Stress ◽

Growth Factors ◽

Vascular Function ◽

Fluid Pressure ◽

Compressive Force ◽

Lymphatic Drainage ◽

Angiogenic Growth Factors ◽

Flow Shear ◽

Flow Shear Stress

As solid tumors develop, a variety of physical stresses arise including growth induced compressive force, matrix stiffening due to desmoplasia, and increased interstitial fluid pressure and altered flow patterns due to leaky vasculature and poor lymphatic drainage [1]. These microenvironmental stresses likely contribute to the abnormal cell behavior that drives tumor progression, and have become an increasingly significant area of cancer research. Of particular importance, is the role of flow shear stress on tumor-endothelial signaling, vascular function, and angiogenesis. Compared to normal vasculature, blood vessels in tumors are poorly functional due to dysregulated expression of angiogenic growth factors, such as vascular endothelial growth factor (VEGF) or the angiopoietins. Also, because of the abnormal vessel structure, blood velocities can be an order of magnitude lower than that of normal microvessels. Recently published work utilizing intravital microscopy to measure blood velocities in mouse mammary fat pad tumors, demonstrated for the first time that shear rate gradients in tumors may help guide branching and growth of new vessels [2]. However, much still remains unknown about how shear stress regulates endothelial organization, permeability, or expression of growth factors within the context of the tumor microenvironment.

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Flow shear stress controls the initiation of neovascularization via heparan sulfate proteoglycans within a biomimetic microfluidic model

Lab on a Chip ◽

10.1039/d0lc00493f ◽

2021 ◽

Author(s):

Ping Zhao ◽

Xiao Liu ◽

Xing Zhang ◽

Li Wang ◽

Haoran Su ◽

...

Keyword(s):

Shear Stress ◽

Heparan Sulfate ◽

Heparan Sulfate Proteoglycans ◽

Flow Shear ◽

Flow Shear Stress

The role of shear stress was investigated in a biomimetic microfluidic model that recapitulates the initial physiological microenvironment of neovascularization.

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Chronic Hydralazine Improves Flow (Shear Stress)-Induced Endothelium-Dependent Dilation in Mouse Mesenteric Resistance Arteries in Vitro

Microvascular Research ◽

10.1006/mvre.2002.2417 ◽

2002 ◽

Vol 64 (1) ◽

pp. 127-134 ◽

Cited By ~ 16

Author(s):

Diane Gorny ◽

Laurent Loufrani ◽

Nathalie Kubis ◽

Bernard I. Lévy ◽

Daniel Henrion

Keyword(s):

Shear Stress ◽

Resistance Arteries ◽

Flow Shear ◽

Flow Shear Stress

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Mechanical Property of TiO2 Micro/Nano Surface Based on the Investigation of Residual Stress, Tensile Force and Fluid Flow Shear Stress: For Potential Application of Cardiovascular Devices

Journal of Nano Research ◽

10.4028/www.scientific.net/jnanor.49.190 ◽

2017 ◽

Vol 49 ◽

pp. 190-201 ◽

Cited By ~ 6

Author(s):

Cong Zhen Han ◽

Jing An Li ◽

Dan Zou ◽

Xiao Luo ◽

Ping Yang ◽

...

Keyword(s):

Residual Stress ◽

Blood Flow ◽

Shear Stress ◽

Surface Energy ◽

Potential Application ◽

Drug Loading ◽

Tube Length ◽

Flow Shear ◽

Cardiovascular Devices ◽

Flow Shear Stress

The micro-patterned TiO2 nanotube has been anticipated for potential application for cardiovascular implanted devices for its excellent drug loading/ release function and biocompatibility. However, its mechanical behavior has rarely been studied as the cardiovascular devices. The tube length is a crucial factor which not only decides the drug loading ability but also influences the devices’ mechanical behavior. Therefore, in this work, the micro-patterned TiO2 nanotubes with different tube length (MNT2, MNT4 and MNT6) were fabricated, and their surface energy, residual stress, tensile tolerability and blood flow shear stress tolerability were determined, respectively. The results showed that the microstructure reduced the surface energy of the nanotubes surfaces, enhanced or reduced surface tensile tolerability when parallel or vertical to the strain orientation, and also increased the nanotubes surfaces residual stress; In addition, both micro/nano and single nano surfaces possessed good blood flow shear stress tolerability. These results indicated that the micro/nano surfaces possesses excellent mechanical properties for surface modification of cardiovascular devices.

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