Shear stress increases inositol trisphosphate levels in human endothelial cells

Nollert, Matthias U.; Eskin, Suzanne G.; McIntire, Larry V.

doi:10.1016/0006-291x(90)91271-s

Cited by 219 publications

(83 citation statements)

References 24 publications

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“…40 - 41 Moreover, shear stress can activate phosphoinositol metabolism and may promote an increase in intracellular calcium. 42 - 43 These events result in the release of local factors, such as nitric oxide, transforming growth factor-/? (TGF-/3), platelet-derived growth factor (PDGF), tissue plasminogen activator, and endothelin, that may participate in vascular remodeling.…”

Section: -33mentioning

confidence: 99%

New perspectives in hypertension research. Potentials of vascular biology.

et al. 1994

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The vessel wall was once considered to be a passive conduit responding to the circulating endocrine system. However, the emergence of molecular and vascular biology in hypertension research has redefined our understanding of the role of the vasculature as a vital organ in the pathogenesis of hypertension. It is now recognized that the vasculature can regulate its own tone by a variety of previously unknown autocrine and/or paracrine vasoactive systems. Recent evidence indicates that the process of vascular remodeling in hypertension appears to be mediated by locally generated factors within the vessel wall. This review examines the implications of this new paradigm in hypertension, focusing on O ver the past half century, the direction of hypertension research has been shaped by a scientific paradigm that has focused on the regulation of systemic neuroendocrine vasoactive systems that control vascular tone and renal fluid-electrolyte homeostasis. This paradigm postulates that hypertension is caused by a disturbance in the physiological homeostatic mechanisms regulating the levels of and/or responses to circulating hormones and sympathetic nervous system activity. In this schema the vasculature is conceptualized as a simple effector system that passively responds to the actions of systemic neuroendocrine factors. However, advances in molecular vascular biology have begun to promote a paradigm shift that has dramatically altered our conception of the role of the vasculature in hypertension. Based on recent studies it has become increasingly clear that the vasculature is itself a complex, integrated organ capable of autonomous generation of locally active factors that mediate changes in tone and structure. This review will examine the implications of this new molecular vascular biology paradigm in hypertension research, focusing on five areas in which vascular biology has had or will have major effects on hypertension research: (1) the discovery of novel endogenous biologically active molecules synthesized by the vessel wall, (2) the elucidation of molecular mechanisms and consequences of vascular remodeling in hypertension, (3) an understanding of the developmental biology of the blood vessel and the relation to pathobiology, (4) the in vivo testing of in vitro hypotheses using in vivo gene transfer, and (5) the development of novel treatment strategies based on vascular molecular biology, such as gene therapy.

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Section: -33mentioning

confidence: 99%

New perspectives in hypertension research. Potentials of vascular biology.

et al. 1994

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“…The mechanical stress generated on the EC layer due to this flow is an important extrinsic factor capable of modifying vessel barrier properties through alteration of the inter-endothelial junctions and the EC-extracellular matrix interactions. [20][21][22][23] It can also activate intracellular signaling events, altering barrier properties like increased intracellular Ca 2þ levels and the generation of inositol trisphosphate, [24][25][26] activation of Rac, 27,28 RhoA-dependent reorganization of the actin cytoskeleton, 21,22,29 and b 1 -integrin-dependent increases in caveolin-1 phosphorylation. 21 Therefore, integration of in vivo levels of flow with the EC culture is important in limiting the chances of the cell monolayer undergoing phenotypic drifts and no longer reflecting in situ characteristics.…”

Section: Introductionmentioning

confidence: 99%

Characterization of vascular permeability using a biomimetic microfluidic blood vessel model

et al. 2017

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The inflammatory response in endothelial cells (ECs) leads to an increase in vascular permeability through the formation of gaps. However, the dynamic nature of vascular permeability and external factors involved is still elusive. In this work, we use a biomimetic blood vessel (BBV) microfluidic model to measure in real-time the change in permeability of the EC layer under culture in physiologically relevant flow conditions. This platform studies the dynamics and characterizes vascular permeability when the EC layer is triggered with an inflammatory agent using tracer molecules of three different sizes, and the results are compared to a transwell insert study. We also apply an analytical model to compare the permeability data from the different tracer molecules to understand the physiological and bio-transport significance of endothelial permeability based on the molecule of interest. A computational model of the BBV model is also built to understand the factors influencing transport of molecules of different sizes under flow. The endothelial monolayer cultured under flow in the BBV model was treated with thrombin, a serine protease that induces a rapid and reversible increase in endothelium permeability. On analysis of permeability data, it is found that the transport characteristics for fluorescein isothiocyanate (FITC) dye and FITC Dextran 4k Da molecules are similar in both BBV and transwell models, but FITC Dextran 70k Da molecules show increased permeability in the BBV model as convection flow (Peclet number > 1) influences the molecule transport in the BBV model. We also calculated from permeability data the relative increase in intercellular gap area during thrombin treatment for ECs in the BBV and transwell insert models to be between 12% and 15%. This relative increase was found to be within range of what we quantified from F-actin stained EC layer images. The work highlights the importance of incorporating flow in in vitro vascular models, especially in studies involving transport of large size objects such as antibodies, proteins, nano/micro particles, and cells. Published by AIP Publishing.

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“…Falcone et al 1993;Oike et al 1994). The suggested mechanisms include Ca¥ release from intracellular stores (Nollert et al 1990;Geiger et al 1992;Shen et al 1992) and Ca¥ entry from the extracellular medium (Schwarz et al 1992). However, a number of investigators were unable to detect any changes in endothelial [Ca¥]é and have proposed other mechanisms of mechanotransduction.…”

Section: Discussionmentioning

confidence: 99%

Effects of Shear Stress on [Ca²⁺]_I and Membrane Potential of Vascular Endothelium of Intact Rat Blood Vessels

Marchenko

Sage

2000

Experimental Physiology

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Shear stress is an important modulator of endothelial function which can affect vessel tone, endothelial morphology and gene transcription. However, the mechanism by which the endothelium detects changes in shear stress is the subject of conflicting reports. The possible contributions of changes in the cytosolic Ca2+ concentration ([Ca2+]i) and of membrane hyperpolarisation are disputed. Here we have investigated the effects of shear stress on these variables in native endothelium in situ in rat aorta and hepatic portal vein. Endothelial [Ca2+]i was recorded using the fluorescent indicator fura‐2. The [Ca2+]i in unstimulated rat aortic endothelium was 86 ± 12 nM (n= 9). Acetylcholine (ACh) evoked relaxation of the aorta and a biphasic increase in endothelial [Ca2+]i. Shear stress that evoked relaxation comparable to that evoked by ACh did not affect the endothelial [Ca2+]i. Endothelial membrane potential was recorded using the patch clamp technique. The resting membrane potentials of rat aortic and portal vein endothelium were ‐47 ± 3.8 mV (n= 14) and ‐68 ± 4.5 mV (n= 9), respectively. Shear stress did not affect the endothelial membrane potential of rat aorta, but evoked a small (‐1.6 ± 0.3 mV, n= 9) hyperpolarisation of the endothelium of rat portal vein in all preparations studied. These results suggest that neither changes in [Ca2+]i nor hyperpolarisation are involved in the reception of shear stress by native rat aortic endothelium in situ, but that shear stress induces small hyperpolarisations of endothelium of portal vein, a mechanism that may be present and of greater physiological significance in other parts of vascular system.

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Shear stress increases inositol trisphosphate levels in human endothelial cells

Cited by 219 publications

References 24 publications

New perspectives in hypertension research. Potentials of vascular biology.

New perspectives in hypertension research. Potentials of vascular biology.

Characterization of vascular permeability using a biomimetic microfluidic blood vessel model

Effects of Shear Stress on [Ca²⁺]_I and Membrane Potential of Vascular Endothelium of Intact Rat Blood Vessels

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Shear stress increases inositol trisphosphate levels in human endothelial cells

Cited by 219 publications

References 24 publications

New perspectives in hypertension research. Potentials of vascular biology.

New perspectives in hypertension research. Potentials of vascular biology.

Characterization of vascular permeability using a biomimetic microfluidic blood vessel model

Effects of Shear Stress on [Ca2+]I and Membrane Potential of Vascular Endothelium of Intact Rat Blood Vessels

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Effects of Shear Stress on [Ca²⁺]_I and Membrane Potential of Vascular Endothelium of Intact Rat Blood Vessels