Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology

Davies, Peter F.

doi:10.1038/ncpcardio1397

Cited by 1,002 publications

(874 citation statements)

References 75 publications

(88 reference statements)

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“…Increase in cardiac output could alter mean fluid shear and affect NO production, as occurs with exercise and as others have reported (15,16,28,31,37). We have not directly measured cardiac output in rats in response to pG z .…”

Section: Discussionmentioning

confidence: 88%

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Low-amplitude pulses to the circulation through periodic acceleration induces endothelial-dependent vasodilatation

Uryash

Wu²,

Bassuk³

et al. 2009

Journal of Applied Physiology

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Uryash A, Wu H, Bassuk J, Kurlansky P, Sackner MA, Adams JA. Low-amplitude pulses to the circulation through periodic acceleration induces endothelial-dependent vasodilatation. J Appl Physiol 106: 1840 -1847, 2009. First published March 26, 2009 doi:10.1152/japplphysiol.91612.2008.-Low-amplitude pulses to the vasculature increase pulsatile shear stress to the endothelium. This activates endothelial nitric oxide (NO) synthase (eNOS) to promote NO release and endothelial-dependent vasodilatation. Descent of the dicrotic notch on the arterial pulse waveform and a-to-b ratio (a/b; where a is the height of the pulse amplitude and b is the height of the dicrotic notch above the end-diastolic level) reflects vasodilator (increased a/b) and vasoconstrictor effects (decreased a/b) due to NO level change. Periodic acceleration (pG z) (motion of the supine body head to foot on a platform) provides systemic additional pulsatile shear stress. The purpose of this study was to determine whether or not pG z applied to rats produced endothelial-dependent vasodilatation and increased NO production, and whether the latter was regulated by the Akt/phosphatidylinositol 3-kinase (PI3K) pathway. Male rats were anesthetized and instrumented, and pG z was applied. Sodium nitroprusside, N G -nitro-L-arginine methyl ester (L-NAME), and wortmannin (WM; to block Akt/PI3K pathway) were administered to compare changes in a/b and mean aortic pressure. Descent of the dicrotic notch occurred within 2 s of initiating pG z. Dose-dependent increase of a/b and decrease of mean aortic pressure took place with SNP. L-NAME produced a dose-dependent rise in mean aortic pressure and decrease of a/b, which was blunted with pG z. In the presence of WM, pGz did not decrease aortic pressure or increase a/b. WM also abolished the pG z blunting effect on blood pressure and a/b of L-NAME-treated animals. eNOS expression was increased in aortic tissue after pG z. This study indicates that addition of low-amplitude pulses to circulation through pG z produces endothelial-dependent vasodilatation due to increased NO in rats, which is mediated via activation of eNOS, in part, by the Akt/PI3K pathway. vascular resistance; N G -nitro-L-arginine methyl ester, wortmannin; nitric oxide ADDED LOW-AMPLITUDE PULSES to the vasculature were generated with periodic acceleration (pG z ). pG z is produced by a motorized platform that repetitively moves the horizontally oriented body sinusoidally in a head to foot direction. Inertia of fluid as the body accelerates and decelerates adds a small-amplitude pulse to the circulation that is superimposed on the natural pulse, increasing pulsatile shear stress to the endothelium (3, 6, 7). In large-animal models, increased pulsatile shear stress activates endothelial nitric oxide (NO) synthase (eNOS) to release NO into the circulation, which, in turn, induces endothelial-dependent pulmonary and systemic vasodilatation, as well as increasing organ blood flows (3,5,6). pG z applied to anesthetized swine increases serum nitrite, which is ...

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Section: Discussionmentioning

confidence: 88%

“…Low-amplitude pulses to the circulation through periodic acceleration induces endothelial-dependent vasodilatation. J Appl Physiol 106: 1840 -1847, 2009. First published March 26, 2009 doi:10.1152/japplphysiol.91612.2008.-Low-amplitude pulses to the vasculature increase pulsatile shear stress to the endothelium.…”

mentioning

confidence: 99%

Low-amplitude pulses to the circulation through periodic acceleration induces endothelial-dependent vasodilatation

Uryash

Wu²,

Bassuk³

et al. 2009

Journal of Applied Physiology

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“…A well‐established concept in arterial endothelial biology is the cause–effect relationship between hemodynamic WSS and gene expression 1, 28, 29, 30. In this study, we identified the regional patterning of WSS and EEC phenotype but have not yet isolated the mechanisms to explain their relationships and how they may be different or similar to arterial ECs.…”

Section: Discussionmentioning

confidence: 99%

Integrated Regional Cardiac Hemodynamic Imaging and RNA Sequencing Reveal Corresponding Heterogeneity of Ventricular Wall Shear Stress and Endocardial Transcriptome

McCormick

Manduchi

Witschey

et al. 2016

JAHA

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BackgroundUnlike arteries, in which regionally distinct hemodynamics are associated with phenotypic heterogeneity, the relationships between endocardial endothelial cell phenotype and intraventricular flow remain largely unexplored. We investigated regional differences in left ventricular wall shear stress and their association with endocardial endothelial cell gene expression.Methods and ResultsLocal wall shear stress was calculated from 4‐dimensional flow magnetic resonance imaging in 3 distinct regions of human (n=8) and pig (n=5) left ventricle: base, adjacent to the outflow tract; midventricle; and apex. In both species, wall shear stress values were significantly lower in the apex and midventricle relative to the base; oscillatory shear index was elevated in the apex. RNA sequencing of the endocardial endothelial cell transcriptome in pig left ventricle (n=8) at a false discovery rate ≤10% identified 1051 genes differentially expressed between the base and the apex and 327 between the base and the midventricle; no differentially expressed genes were detected at this false discovery rate between the apex and the midventricle. Enrichment analyses identified apical upregulation of genes associated with translation initiation including mammalian target of rapamycin, and eukaryotic initiation factor 2 signaling. Genes of mitochondrial dysfunction and oxidative phosphorylation were also consistently upregulated in the left ventricular apex, as were tissue factor pathway inhibitor (mean 50‐fold) and prostacyclin synthase (5‐fold)—genes prominently associated with antithrombotic protection.ConclusionsWe report the first spatiotemporal measurements of wall shear stress within the left ventricle and linked regional hemodynamics to heterogeneity in ventricular endothelial gene expression, most notably to translation initiation and anticoagulation properties in the left ventricular apex, in which oscillatory shear index is increased and wall shear stress is decreased.

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“…Both these conditions, according to Laplace law, make these plaques highly susceptible to rupture [13,31]. Moreover, it has to be emphasized that these calcified nodules, protruding into the vascular lumen, can induce flow disturbances, increase the stiffness and reduce the elasticity of the vessel wall [32].…”

Section: Discussionmentioning

confidence: 99%

Asymptomatic carotid plaque rupture with unexpected thrombosis over a non-canonical vulnerable lesion

et al. 2011

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a b s t r a c tObjective: Several studies have demonstrated that carotid plaque rupture and thrombosis represent the most important factors correlated with the onset of acute cerebrovascular symptoms. Nevertheless, ruptured thrombotic plaques have been described also in asymptomatic patients. What still needs to be clarified is why a plaque rupture leads either to an acute ischemic syndrome or, in a minor group of patients, remains asymptomatic. The purpose of this study was to systematically compare the histologic features of thrombotic plaques both in asymptomatic and symptomatic patients in order to identify specific findings that could explain the peculiar clinical behavior that characterizes each of the clinical settings. Methods: A total of 157 thrombotic plaques from 60 asymptomatic patients and 97 with major stroke who consecutively underwent CEA were serially sectioned and studied by histology. Results: A minute cap disruption very frequently characterizes thrombotic plaques of asymptomatic patients and it was always smaller than large ulcers observed in thrombotic symptomatic plaques (651 ± 687 m vs. 4150 ± 3526, p = 0.001). In asymptomatics this typical feature was associated with fewer inflammatory cells (20.1 ± 8.8 vs. 33.9 ± 26.1 cells × hpf, p = 0.001), smaller lipidic-necrotic core (33.9% ± 2.9% vs. 42.0% ± 2.4%; p = 0.04) and larger calcification (16.2 ± 12.8% vs. 8.1 ± 12.2%, p = 0.02). Symptomatic patients with thrombotic plaques showed higher incidence of metabolic syndrome (p = 0.002) and moderate-high Framingham risk scores (p = 0.001) comparing to asymptomatic individuals. Conclusion: The transformation from a stable to a vulnerable plaque is a gradual process in the natural history of the disease and plaque rupture is an event not necessarily occurring at a late phase but also at earlier one. In this case, the rupture will be most likely smaller and clinically asymptomatic.

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Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology

Cited by 1,002 publications

References 75 publications

Low-amplitude pulses to the circulation through periodic acceleration induces endothelial-dependent vasodilatation

Low-amplitude pulses to the circulation through periodic acceleration induces endothelial-dependent vasodilatation

Integrated Regional Cardiac Hemodynamic Imaging and RNA Sequencing Reveal Corresponding Heterogeneity of Ventricular Wall Shear Stress and Endocardial Transcriptome

Asymptomatic carotid plaque rupture with unexpected thrombosis over a non-canonical vulnerable lesion

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