Shear Stress-induced Redistribution of Vascular Endothelial-Protein-tyrosine Phosphatase (VE-PTP) in Endothelial Cells and Its Role in Cell Elongation

Mantilidewi, Kemala Isnainiasih; Murata, Yoji; Mori, Munemasa; Otsubo, Chihiro; Kotani, Takenori; Kusakari, Shinya; Ohnishi, Hiroshi; Matozaki, Takashi

doi:10.1074/jbc.m113.529503

Cited by 23 publications

(16 citation statements)

References 47 publications

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“…Endothelial cells form the inner lining of blood vessels and are continuously exposed to mechanical stimuli such as stretch and shear stress generated by blood flow and pressure, respectively. These stresses play an important role in the regulation of endothelial cell function, including proliferation, changes in cell motility and migration, as well as changes in cell morphology [34]. In addition, shear stress generated by blood flow affects the characteristics of cell adhesion receptors [35e38].…”

Section: Discussionmentioning

confidence: 99%

ADAM9 silencing inhibits breast tumor cells transmigration through blood and lymphatic endothelial cells

Micocci¹,

Moritz²,

Lino³

et al. 2016

Biochimie

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Section: Discussionmentioning

confidence: 99%

ADAM9 silencing inhibits breast tumor cells transmigration through blood and lymphatic endothelial cells

Micocci¹,

Moritz²,

Lino³

et al. 2016

Biochimie

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“…In addition to Tie1, laminar shear stimulates a polarized subcellular distribution of VE-PTP [144], and down-regulates Ang2 expression via KLF2 transcription-factor mediated miRNA regulation [145,146]. In vivo Ang2 is expressed in the atherosclerosis-prone region of the lesser curvature of the aortic arch, which experiences disturbed flow pattern [146].…”

Section: Ang–tie System In Vascular Diseasesmentioning

confidence: 99%

Angiopoietin–Tie signalling in the cardiovascular and lymphatic systems

Eklund¹,

Kangas²,

2016

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Endothelial cells that form the inner layer of blood and lymphatic vessels are important regulators of vascular functions and centrally involved in the pathogenesis of vascular diseases. In addition to the vascular endothelial growth factor (VEGF) receptor pathway, the angiopoietin (Ang)–Tie system is a second endothelial cell specific ligand–receptor signalling system necessary for embryonic cardiovascular and lymphatic development. The Ang–Tie system also regulates postnatal angiogenesis, vessel remodelling, vascular permeability and inflammation to maintain vascular homoeostasis in adult physiology. This system is implicated in numerous diseases where the vasculature has an important contribution, such as cancer, sepsis, diabetes, atherosclerosis and ocular diseases. Furthermore, mutations in the TIE2 signalling pathway cause defects in vascular morphogenesis, resulting in venous malformations and primary congenital glaucoma. Here, we review recent advances in the understanding of the Ang–Tie signalling system, including cross-talk with the vascular endothelial protein tyrosine phosphatase (VE-PTP) and the integrin cell adhesion receptors, focusing on the Ang–Tie system in vascular development and pathogenesis of vascular diseases.

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“…Endocytosis has emerged as an important circuitry in the onset and progression of EMT/EndMT, enabling membrane trafficking, receptor recycling and degradation, ultimately promoting mesenchymal features, such as changes in cell polarity, cell-cell contact and cell migration 16 . Endocytic activity in endothelial cells has previously been shown to be regulated by shear stress 35 , 36 , and we have recently demonstrated an increased endocytic activity in the BAV-ND endothelium associated with an increased accumulation of degrading material 9 . These results are in line with previous studies investigating the effect of oscillatory shear stress on EMT/EndMT using different experimental setups, including flow systems and type of endothelial cells 37 – 39 .…”

Section: Discussionmentioning

confidence: 61%

Altered DNA methylation indicates an oscillatory flow mediated epithelial-to-mesenchymal transition signature in ascending aorta of patients with bicuspid aortic valve

Björck

Pulignani

et al. 2018

Sci Rep

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Disturbed flow has been suggested to contribute to aneurysm susceptibility in bicuspid aortic valve (BAV) patients. Lately, flow has emerged as an important modulator of DNA methylation. Hear we combined global methylation analysis with in vitro studies of flow-sensitive methylation to identify biological processes associated with BAV-aortopathy and the potential contribution of flow. Biopsies from non-dilated and dilated ascending aortas were collected from BAV (n = 21) and tricuspid aortic valve (TAV) patients (n = 23). DNA methylation and gene expression was measured in aortic intima-media tissue samples, and in EA.hy926 and primary aortic endothelial cells (ECs) isolated from BAV and TAV exposed to oscillatory (±12 dynes/cm2) or laminar (12 dynes/cm2) flow. We show methylation changes related to epithelial-mesenchymal-transition (EMT) in the non-dilated BAV aorta, associated with oscillatory flow related to endocytosis. The results indicate that the flow-response in BAV ECs involves hypomethylation and increased expression of WNT/β-catenin genes, as opposed to an angiogenic profile in TAV ECs. The EMT-signature was exasperated in dilated BAV aortas. Aberrant EMT in BAV aortic walls could contribute to increased aneurysm susceptibility, and may be due to disturbed flow-exposure. Perturbations during the spatiotemporally related embryonic development of ascending aorta and semilunar valves can however not be excluded.

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Shear Stress-induced Redistribution of Vascular Endothelial-Protein-tyrosine Phosphatase (VE-PTP) in Endothelial Cells and Its Role in Cell Elongation

Cited by 23 publications

References 47 publications

ADAM9 silencing inhibits breast tumor cells transmigration through blood and lymphatic endothelial cells

ADAM9 silencing inhibits breast tumor cells transmigration through blood and lymphatic endothelial cells

Angiopoietin–Tie signalling in the cardiovascular and lymphatic systems

Altered DNA methylation indicates an oscillatory flow mediated epithelial-to-mesenchymal transition signature in ascending aorta of patients with bicuspid aortic valve

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