Regulation of Endothelial Activation and Vascular Inflammation by Shear Stress

Nayak, Annapurna; König, Carola S.; Kishore, Uday; Evans, Paul C.

doi:10.1007/978-1-4614-4376-6_6

Cited by 3 publications

(3 citation statements)

References 36 publications

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Section: Introductionmentioning

confidence: 99%

“… 13 It is suggested that atherosclerosis is related to altered wall shear stress (WSS), particularly low WSS, due to a decrease in nitric oxide synthase production, vasodilation and cell repair. 14 – 17 Malek et al 18 identified that WSS >1.5 Pa induces endothelial quiescence and an atheroprotective gene expression profile, while values <0.4 Pa were found at atherosclerosis-prone sites resulting in stimulating an atherogenic phenotype. Gijsen et al 19 classed WSS between 0 and 1 Pa as ‘low’ while the range from 1 to 7 Pa was being classed as ‘normal/high’ as in cultured endothelium the range from 1.2 to 1.5 Pa was found to be most frequently atheroprotectively associated though a plaque stenosis could see values of 7 Pa and higher.…”

Section: Introductionmentioning

confidence: 99%

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The association of peak systolic velocity in the carotid artery with coronary heart disease: A study based on portable ultrasound

König

Atherton

Cavazzuti

et al. 2021

Proc Inst Mech Eng H

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Cardiovascular disease (CVD) is the highest cause of death globally with more people dying annually from it than from any other cause. CVD is associated with modifiable risk factors (dyslipidaemia, hypertension and diabetes) and treating each of these factors lowers the risk of CVD. It is impossible to estimate the benefit of risk factor modification in the individual patient and extrapolating data from multiple trials is difficult. It would be useful to have a marker of risk that accurately estimates real time risk by measuring blood flow factors associated with the pathogenesis of atheroma. The aim of this preliminary study was to validate a low-cost measurement technique for obtaining blood flow velocity profiles and assess whether any of the measured and calculated factors, based on computational fluid dynamics (CFD) simulation, known to be associated with atheroma was associated with coronary heart disease (CHD), thus establishing its feasibility and acceptability as a clinical tool and suggesting areas for future research. Our study identified (i) that mean peak systolic (PS) velocity being associated with CHD; individuals without CHD: mean (SD) = 62.8 (16.1) cm/s, with CHD: mean (SD) = 53.6 (17.3) cm/s, p = 0.042; and (ii) that low-cost, portable ultrasound, which is routinely available in general practice, is a suitable assessment tool.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The association of peak systolic velocity in the carotid artery with coronary heart disease: A study based on portable ultrasound

König

Atherton

Cavazzuti

et al. 2021

Proc Inst Mech Eng H

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“…The effects of low shear stress on the regulation of endothelial activation have been reported. 32 Low shear stress leads to EC activation and activated ECs can mediate platelet adhesion and subsequent thrombus formation.…”

mentioning

confidence: 99%

Hemodynamic Assessment of Hollow-Fiber Membrane Oxygenators Using Computational Fluid Dynamics in Heterogeneous Membrane Models

Dipresa

Kalozoumis

Pflaum

et al. 2021

Journal of Biomechanical Engineering

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Extracorporeal membrane oxygenation (ECMO) has been used clinically for more than 40 years as a bridge to transplantation, with hollow-fiber membrane (HFM) oxygenators gaining in popularity due to their high gas transfer and low flow resistance. In spite of the technological advances in ECMO devices, the inevitable contact of the perfused blood with the polymer hollow-fiber gas-exchange membrane, and the subsequent thrombus formation, limits their clinical usage to only 2-4 weeks. In addition, the inhomogeneous flow in the device can further enhance thrombus formation and limit gas-transport efficiency. Endothelialisation of the blood contacting surfaces of ECMO devices offers a potential solution to their inherent thrombogenicity. However, abnormal shear stresses and inhomogeneous blood flow might affect the function and activation status of the seeded endothelial cells (ECs). In this study, the blood flow through two HFM oxygenators, including the commercially-available iLA® MiniLung Petite Novalung (Xenios AG, Germany) and an experimental one for the rat animal model, was modelled using computational fluid dynamics (CFD), with a view to assessing the magnitude and distribution of the shear stress on the wall of the hollow fibers and flow fields in the oxygenators. This work demonstrated significant inhomogeneity in the flow dynamics of both oxygenators, with regions of high hollow-fiber wall shear stress and regions of stagnant flow, implying both regions of increased flow-induced blood damage and a variable flow-induced stimulation on seeded ECs in a biohybrid setting.

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Astrocyte Mechano-Activation by High-Rate Overpressure Involves Alterations in Structural and Junctional Proteins

Hlavac¹,

VandeVord²

2019

Front. Neurol.

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Primary blast neurotrauma represents a unique injury paradigm characterized by high-rate overpressure effects on brain tissue. One major hallmark of blast neurotrauma is glial reactivity, notably prolonged astrocyte activation. This cellular response has been mainly defined in primary blast neurotrauma by increased intermediate filament expression. Because the intermediate filament networks physically interface with transmembrane proteins for junctional support, it was hypothesized that cell junction regulation is altered in the reactive phenotype as well. This would have implications for downstream transcriptional regulation via signal transduction pathways like nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Therefore, a custom high-rate overpressure simulator was built for in vitro testing using mechanical conditions based on intracranial pressure measurements in a rat model of blast neurotrauma. Primary rat astrocytes were exposed to isolated high-rate mechanical stimulation to study cell junction dynamics in relation to their mechano-activation. First, a time course for “classical” features of reactivity was devised by evaluation of glial fibrillary acidic protein (GFAP) and proliferating cell nuclear antigen (PCNA) expression. This was followed by gene and protein expression for both gap junction (connexins) and anchoring junction proteins (integrins and cadherins). Signal transduction analysis was carried out by nuclear localization of two molecules, NF-κB p65 and mitogen-activated protein kinase (MAPK) p38. Results indicated significant increases in connexin-43 expression and PCNA first at 24 h post-overpressure ( p < 0.05), followed by structural reactivity (via increased GFAP, p < 0.05) corresponding to increased anchoring junction dynamics at 48 h post-overpressure ( p < 0.05). Moreover, increased phosphorylation of focal adhesion kinase (FAK) was observed in addition to increased nuclear localization of both p65 and p38 ( p < 0.05) during the period of structural reactivity. To evaluate the transcriptional activity of p65 in the nucleus, electrophoretic mobility shift assay was conducted for a binding site on the promoter region for intracellular adhesion molecule-1 (ICAM-1), an antagonist of tight junctions. A significant increase in the interaction of nuclear proteins with the NF-κB site on the ICAM-1 corresponded to increased gene and protein expression of ICAM-1 ( p < 0.05). Altogether, these results indicate multiple targets and corresponding signaling pathways which involve cell junction dynamics in the mechano-activation of astrocytes following high-rate overpressure.

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Regulation of Endothelial Activation and Vascular Inflammation by Shear Stress

Cited by 3 publications

References 36 publications

The association of peak systolic velocity in the carotid artery with coronary heart disease: A study based on portable ultrasound

The association of peak systolic velocity in the carotid artery with coronary heart disease: A study based on portable ultrasound

Hemodynamic Assessment of Hollow-Fiber Membrane Oxygenators Using Computational Fluid Dynamics in Heterogeneous Membrane Models

Astrocyte Mechano-Activation by High-Rate Overpressure Involves Alterations in Structural and Junctional Proteins

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