Molecular basis of the effects of shear stress on vascular endothelial cells

Li, Yi-Shuan J.; Haga, Jason; Chien, Shu

doi:10.1016/j.jbiomech.2004.09.030

Cited by 744 publications

(644 citation statements)

References 214 publications

(240 reference statements)

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“…In addition, it can provide cells with directional information about blood flow to which EC respond with reorientation to the local shear axis (Topper and Gimbrone, 1999;Noria et al, 2004). Mechanical deformation of the cytoskeleton also links the apparently non-related shear sensors that have been described to date, including integrins, cell-cell adhesion molecules, tyrosine kinase receptors, G protein-coupled receptors, and ion channels for Ca 2ϩ and K ϩ (Lehoux et al, 2006;Li et al, 2005;Nauli et al, 2008). All these proteins are connected to the cytoskeleton, either directly or through linker proteins.…”

Section: Discussionmentioning

confidence: 99%

Primary cilia sensitize endothelial cells for fluid shear stress

Hierck

Heiden

Alkemade

et al. 2008

Developmental Dynamics

155

108

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Primary cilia are mechanosensors for fluid shear stress, and are involved in a number of syndromes and congenital anomalies. We identified endothelial cilia in areas of low shear stress in the embryonic heart. The objective of the present study was to demonstrate the role of primary cilia in mechanosensing. Ciliated embryonic endothelial cells were cultured from the heart, and non-ciliated cells from the arteries. Nonciliated cells that were subjected to fluid shear stress showed significantly less induction of the shear marker Krü ppel-Like Factor-2, as compared to ciliated cells. In addition, ciliated cells from which the cilia were chemically removed show a similar decrease in flow response. This shows that primary cilia sensitize endothelial cells for fluid shear stress. In addition, we targeted and stabilized the connection of the cilium to the cytoplasm by treatment with Colchicine and Taxol/Paclitaxel, respectively, and show that microtubular integrity is essential to sense shear stress. Developmental Dynamics 237:725-735, 2008.

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Section: Discussionmentioning

confidence: 99%

Primary cilia sensitize endothelial cells for fluid shear stress

Hierck

Heiden

Alkemade

et al. 2008

Developmental Dynamics

155

108

View full text Add to dashboard Cite

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“…This hemodynamic stimulus activates numerous mechanoreceptors on the endothelium such as integrins, G protein-coupled receptors, cell adhesion molecules, ion channels and receptor tyrosine kinases (Chien, 2007). Shear stress also activates numerous signaling molecules such as Protein kinase C, Focal adhesion kinase, c-Src, Rho family GTPases, Phosphoinositide 3-kinases and Mitogen activated protein kinases (MAPKs) (Li et al, 2005). Transcription factors such as Ets-1 (Milkiewicz et al, 2008), NF-κB, Krüppel-like factor 2 (Chien, 2007), c-Myc, Activator protein 1 and T-cell factor (Li et al, 2005) are known to be regulated by shear stress.…”

Section: Introductionmentioning

confidence: 99%

p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress‐induced angiogenesis

Gee

Milkiewicz

Haas

2009

Journal Cellular Physiology

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Increased capillary shear stress induces angiogenesis in skeletal muscle, but the signaling mechanisms underlying this response are not known. We hypothesize that shear stress-dependent activation of vascular endothelial growth factor receptor 2 (VEGFR2) causes p38 and ERK1/2 phosphorylation, which contribute to shear stress-induced angiogenesis. Skeletal muscle microvascular endothelial cells were sheared (12 dynes/cm 2 , 0.5-24 hours). VEGFR2-Y1214 phosphorylation increased in response to elevated shear stress and VEGF stimulation. p38 and ERK1/2 phosphorylation increased at 2 hours of shear stress, but only p38 remained phosphorylated at 6 and 24 hours of shear stress. VEGFR2 inhibition abrogated p38, but not ERK1/2 phosphorylation. VEGF production was increased in response to shear stress at 6 hours, and this increased production was abolished by p38 inhibition. Male Sprague-Dawley rats were administered prazosin (50 mg/L drinking water, 1, 2, 4 or 7 days) to induce chronically elevated capillary shear stress in skeletal muscle. In some experiments, mini-osmotic pumps were used to dispense p38 inhibitor SB203580 or its inactive analog SB202474, to the extensor digitorum longus (EDL) of control and prazosin treated rats. Immunostaining and Western blotting showed increases in p38 phosphorylation in capillaries from rats treated with prazosin for 2 days but returned to basal levels at 4 and 7 days. p38 inhibition abolished the increase in capillary to muscle fibre ratio seen after 7 days of prazosin treatment. Our data suggest that p38 activation is necessary for shear stress-dependent angiogenesis.

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“…Dysfunction in barrier maintenance is a hallmark and often the underlying cause of many cardiovascular pathologies. While a host of soluble factors including growth factors, circulating lipids, and reactive oxygen species chemically signal to endothelial cells, hemodynamic forces locally and acutely regulate vascular permeability by remodeling endothelial cell-cell junctions and the cytoskeleton 6 . The shear stress of steady, laminar flow improves barrier integrity through stabilization of cell-cell junctions, while perfusion defects increase vascular permeability and contribute to pathogenesis of cardiovascular diseases including atherosclerosis 7 , stroke 8 , and myocardial infarction 9 .…”

mentioning

confidence: 99%

A non-canonical Notch complex regulates adherens junctions and vascular barrier function

Polacheck

Kutys

Yang

et al. 2017

Nature

262

315

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The vascular barrier that separates blood from tissues is actively regulated by the endothelium and is essential for transport, inflammation, and hemostasis1. Hemodynamic shear stress plays a critical role in maintaining endothelial barrier function2, but how this occurs remains unknown. Here, using an engineered organotypic model of perfused microvessels and confirming in mouse models, we identify that activation of the Notch1 transmembrane receptor directly regulates vascular barrier function through a non-canonical, transcription independent signaling mechanism that drives adherens junction assembly. Shear stress triggers Dll4-dependent proteolytic activation of Notch1 to reveal the Notch1 transmembrane domain – the key domain that mediates barrier establishment. Expression of the Notch1 transmembrane domain is sufficient to rescue Notch1 knockout-induced defects in barrier function, and does so by catalyzing the formation of a novel receptor complex in the plasma membrane consisting of VE-cadherin, the transmembrane protein tyrosine phosphatase LAR, and the Rac1 GEF Trio. This complex activates Rac1 to drive adherens junction assembly and establish barrier function. Canonical Notch transcriptional signaling is highly conserved throughout metazoans and is required for many processes in vascular development, including arterial-venous differentiation3, angiogenesis4, and remodeling5; here, we establish the existence of a previously unappreciated non-canonical cortical signaling pathway for Notch1 that regulates vascular barrier function, and thus provide a mechanism by which a single receptor might link transcriptional programs with adhesive and cytoskeletal remodeling.

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Molecular basis of the effects of shear stress on vascular endothelial cells

Cited by 744 publications

References 214 publications

Primary cilia sensitize endothelial cells for fluid shear stress

Primary cilia sensitize endothelial cells for fluid shear stress

p38 MAPK activity is stimulated by vascular endothelial growth factor receptor 2 activation and is essential for shear stress‐induced angiogenesis

A non-canonical Notch complex regulates adherens junctions and vascular barrier function

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