Temporal Gradients in Shear, but Not Spatial Gradients, Stimulate Endothelial Cell Proliferation

White, Charles R.; Haidekker, Mark A.; Bao, Xuping; Frangos, John A.

doi:10.1161/01.cir.103.20.2508

Cited by 159 publications

(133 citation statements)

References 18 publications

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“…The HSSGs examined in this study vary from 0 to Ϸ2,500 dyne͞cm 2 per cm (1 dyne ϭ 10 N) and are Ͼ1 order of magnitude greater than other flow chamber designs (17) and closer to those observed near arterial bifurcations and branch sites (1,18). These high shear gradients are of special interest in atherogenesis, because it has been proposed that these regions are prone to lesion development (3,19,20). The present study attempts to explain these various observations within the context of a new mechanical model for the actin cytoskeleton.…”

mentioning

confidence: 58%

The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: A “bumper-car” model

Thi

Tarbell

Weinbaum

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

289

308

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We propose a conceptual model for the cytoskeletal organization of endothelial cells (ECs) based on a major dichotomy in structure and function at basal and apical aspects of the cells. Intracellular distributions of filamentous actin (F-actin), vinculin, paxillin, ZO-1, and Cx43 were analyzed from confocal micrographs of rat fat-pad ECs after 5 h of shear stress. With intact glycocalyx, there was severe disruption of the dense peripheral actin bands (DPABs) and migration of vinculin to cell borders under a uniform shear stress (10.5 dyne͞cm 2 ; 1 dyne ‫؍‬ 10 N). This behavior was augmented in corner flow regions of the flow chamber where high shear stress gradients were present. In striking contrast, no such reorganization was observed if the glycocalyx was compromised. These results are explained in terms of a ''bumper-car'' model, in which the actin cortical web and DPAB are only loosely connected to basal attachment sites, allowing for two distinct cellular signaling pathways in response to fluid shear stress, one transmitted by glycocalyx core proteins as a torque that acts on the actin cortical web (ACW) and DPAB, and the other emanating from focal adhesions and stress fibers at the basal and apical membranes of the cell. mechanotransduction ͉ actin cortical web ͉ dense peripheral actin band H emodynamic shearing stresses on endothelial cells (ECs) are widely recognized as playing a vital role in the regulation of vessel wall remodeling, cellular signaling, mass transport, red and white cell interaction, and atherogenesis (1-3). The possible roles of the endothelial glycocalyx (EG) in this regulation as a molecular sieve, as a barrier and modulator of interactions between blood cells and ECs, and as a mechanotransducer of fluid shear stress have been studied more recently (4-7). Relatively little is known about the specific proteins in the EG, although hyaluronan, chondroitin, and heparan sulfate play a significant role in its assembly (8, 9). In the early 1990s, investigators first observed that the shear-induced dilation of small arteries was abolished when sialic acids were removed from the EG by neuraminidase (10). Florian et al. (11) recently verified the presence of heparan sulfate proteoglycan (HSPG) in the glycocalyx of cultured bovine aortic ECs and demonstrated that partial removal of HSPG with heparinase completely blocked shear-induced NO release. A puzzling and still not understood consequence of EG degradation was the observation that shear-induced NO production was greatly inhibited without apparent effect on shear-dependent vasodilation due to prostaglandin I 2 release (12). Squire et al. (13) showed that the ultrastructural organization of the EG was quasiperiodic, anchored to a geodesic-like scaffold of hexagonally arranged filamentous actin (F-actin) filaments forming an actin cortical web (ACW) (14) just beneath the plasmalemma. A fundamental question addressed in ref. 7 is how fluid shear stresses acting at the surface of the EG are transmitted to this ACW if there is essentially ...

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mentioning

confidence: 58%

The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: A “bumper-car” model

Thi

Tarbell

Weinbaum

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

289

308

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“…While human in vivo studies typically describe shear stress as a mean construct, numerous secondary phenomena associated with flow, including pulsatile flow, retrograde flow, and flow turbulence, can influence the regulation of endothelial cells [67][68][69][70][71][72] .…”

Section: Importance Of the Velocity Profilementioning

confidence: 99%

“…5). In vitro studies suggest that these two distinct fluid stimuli (velocity acceleration vs. steady shear) regulate short-and longterm endothelial function via independent biomechanical pathways 70,71,[73][74][75] . Studies have shown that the rate of velocity acceleration can affect the progression of atherosclerosis 70,73,76) , endothelial cell function 71 , 74) , mechanotransduction 77,78) , calcium kinetics 79,80) , and vascular tone 81,82) .…”

Section: Velocity Acceleration and Endothelial Functionmentioning

confidence: 99%

Use of Ultrasound for Non-Invasive Assessment of Flow-Mediated Dilation

Stoner

Sabatier

2012

JAT

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The pathological complications of atherosclerosis, namely heart attacks and strokes, remain the leading cause of mortality in the Western world. Preceding atherosclerosis is endothelial dysfunction. There is therefore interest in the application of non-invasive clinical tools to assess endothelial function. The flow-mediated dilation (FMD) test is the standard tool used to assess endothelial function. Reduced FMD is an early marker of atherosclerosis and has been noted for its capacity to predict future cardiovascular disease events. This review discusses the measurement of endothelial function using ultrasound, with a focus on the FMD technique.

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“…Shear-induced signaling cascades and changes in endothelial cell morphology have been reviewed extensively (20,21,55). Shear stress can induce changes in endothelial cell proliferation (92), membrane fluidity (9), and cell morphology (62,96).…”

Section: Techniques For Mechanically Probing Cellsmentioning

confidence: 99%

Cell mechanics and mechanotransduction: pathways, probes, and physiology

Huang

Kamm²,

Lee³

2004

American Journal of Physiology-Cell Physiology

487

367

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not only a complex biochemical environment but also a diverse biomechanical environment. How cells respond to variations in mechanical forces is critical in homeostasis and many diseases. The mechanisms by which mechanical forces lead to eventual biochemical and molecular responses remain undefined, and unraveling this mystery will undoubtedly provide new insight into strengthening bone, growing cartilage, improving cardiac contractility, and constructing tissues for artificial organs. In this article we review the physical bases underlying the mechanotransduction process, techniques used to apply controlled mechanical stresses on living cells and tissues to probe mechanotransduction, and some of the important lessons that we are learning from mechanical stimulation of cells with precisely controlled forces.cytoskeleton; micromanipulation; cell signaling ALL LIVING ORGANISMS face mechanical forces, from the fluid forces around a bacterium to the high forces in a human knee during stair climbing. The process of converting physical forces into biochemical signals and integrating these signals into the cellular responses is referred to as mechanotransduction. Although this review cannot cover all that has been discovered about mechanotransduction, we discuss the molecule-and cell-level structures that may participate in mechanotransduction, provide an overview of prominent techniques currently used for exerting mechanical stresses on cells, and conclude with an overview of the tissue-level response to mechanical signaling. FORCE TRANSDUCTION PATHWAYS AND SIGNALINGForce transmission pathways at the cellular and subcellular scales. Understanding the molecular basis for mechanotransduction requires knowledge of the magnitude and distribution of forces throughout the cell at the molecular scale. At present, we have sufficient information to measure molecular scale forces in only a very few cases. We can, however, analyze the mechanisms by which force is transmitted throughout the cell and use that as a basis for speculation about the molecular mechanisms of mechanotransduction. A variety of different methods have been used to mechanically stimulate a cell, and the cellular response is multifaceted and diverse. Similarly, there are likely to be a variety of sensing mechanisms and locations within the cell where forces can be transduced from a mechanical to a biochemical signal. Despite this apparent complexity, it is probable that cells stimulated in different ways are activated by similar mechanisms at the molecular level. To identify these commonalities, it is useful to consider how externally applied forces are transmitted into and throughout the cell, as well as the magnitudes and distribution of force corresponding to these different methods of stimulation.Both continuum and microstructural approaches have been used to determine force distributions. In the case of a continuum model, the details of the microstructure are ignored, and the forces transmitted via the individual microstructural elements are described in...

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Temporal Gradients in Shear, but Not Spatial Gradients, Stimulate Endothelial Cell Proliferation

Cited by 159 publications

References 18 publications

The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: A “bumper-car” model

The role of the glycocalyx in reorganization of the actin cytoskeleton under fluid shear stress: A “bumper-car” model

Use of Ultrasound for Non-Invasive Assessment of Flow-Mediated Dilation

Cell mechanics and mechanotransduction: pathways, probes, and physiology

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