Control of vascular permeability by adhesion molecules

Sarelius, Ingrid H.; Glading, Angela

doi:10.4161/21688370.2014.985954

Cited by 62 publications

(39 citation statements)

References 134 publications

(119 reference statements)

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“…Our data also demonstrate that VEGFR2-mediated VE-cadherin phosphorylation is Src-dependent: (a) VE-cadherin was phosphorylated upon cells stimulation with VEGF; this effect was abolished by Src inhibitor; and (b) pretreatment with Src inhibitor suppressed CS-induced VE-cadherin phosphorylation. These results demonstrate a signaling mechanism of VEGFR2-mediated Src-dependent VE-cadherin phosphorylation (58,59). The importance of AJ-associated VE-cadherin for the control of VEGFR2 activity is further illustrated by experiments with EC incubation with VE-cadherin blocking antibody BV-9, which significantly increased VEGFR2 tyrosine phosphorylation.…”

Section: Discussionmentioning

confidence: 65%

Activation of Vascular Endothelial Growth Factor (VEGF) Receptor 2 Mediates Endothelial Permeability Caused by Cyclic Stretch

Tian

Gawlak

O’Donnell

et al. 2016

Journal of Biological Chemistry

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High tidal volume mechanical ventilation and the resultant excessive mechanical forces experienced by lung vascular endothelium are known to lead to increased vascular endothelial leak, but the underlying molecular mechanisms remain incompletely understood. One reported mechanotransduction pathway of increased endothelial cell (EC) permeability caused by high magnitude cyclic stretch (18% CS) involves CS-induced activation of the focal adhesion associated signalosome, which triggers Rho GTPase signaling. This study identified an alternative pathway of CS-induced EC permeability. We show here that high magnitude cyclic stretch (18% CS) rapidly activates VEGF receptor 2 (VEGFR2) signaling by dissociating VEGFR2 from VE-cadherin at the cell junctions. This results in VEGFR2 activation, Src-dependent VE-cadherin tyrosine phosphorylation, and internalization leading to increased endothelial permeability. This process is also accompanied by CS-induced phosphorylation and internalization of PECAM1. Importantly, CSinduced endothelial barrier disruption was attenuated by VEGFR2 inhibition. 18% CS-induced EC permeability was linked to dissociation of cell junction scaffold afadin from the adherens junctions. Forced expression of recombinant afadin in pulmonary endothelium attenuated CS-induced VEGFR2 and VE-cadherin phosphorylation, preserved adherens junction integrity and VEGFR2⅐VE-cadherin complex, and suppressed CS-induced EC permeability. This study shows for the first time a mechanism whereby VEGFR2 activation mediates EC permeability induced by pathologically relevant cyclic stretch. In this mechanism, CS induces dissociation of the VEcadherin⅐VEGFR2 complex localized at the adherens juctions, causing activation of VEGFR2, VEGFR2-mediated Src-dependent phosphorylation of VE-cadherin, disassembly of adherens junctions, and EC barrier failure.

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Section: Discussionmentioning

confidence: 65%

Activation of Vascular Endothelial Growth Factor (VEGF) Receptor 2 Mediates Endothelial Permeability Caused by Cyclic Stretch

Tian

Gawlak

O’Donnell

et al. 2016

Journal of Biological Chemistry

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“…[66][67][68] Moreover, ICAM-1 has been shown to regulate EC permeability in healthy and inflamed tissue. 44,69,70 Intriguingly, whereas in healthy tissue, ICAM-1 signaled through PKC activation to control barrier function, following inflammatory stimulation, ICAM-1 engagement by circulating leukocytes led to Src kinase activation to increase solute permeability. 44 ICAM-1 was also shown to activate JNK and lead to internalization of VE-cadherin, 70 causing disruption of the EC junction and impairment of EC barrier function.…”

Section: Icam-1 Regulates Endothelial and Epithelial Barrier Functionmentioning

confidence: 99%

ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis

Bui

Wiesolek

Sumagin

2020

Journal of Leukocyte Biology

591

318

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ICAM‐1 is a cell surface glycoprotein and an adhesion receptor that is best known for regulating leukocyte recruitment from circulation to sites of inflammation. However, in addition to vascular endothelial cells, ICAM‐1 expression is also robustly induced on epithelial and immune cells in response to inflammatory stimulation. Importantly, ICAM‐1 serves as a biosensor to transduce outside‐in‐signaling via association of its cytoplasmic domain with the actin cytoskeleton following ligand engagement of the extracellular domain. Thus, ICAM‐1 has emerged as a master regulator of many essential cellular functions both at the onset and at the resolution of pathologic conditions. Because the role of ICAM‐1 in driving inflammatory responses is well recognized, this review will mainly focus on newly emerging roles of ICAM‐1 in epithelial injury‐resolution responses, as well as immune cell effector function in inflammation and tumorigenesis. ICAM‐1 has been of clinical and therapeutic interest for some time now; however, several attempts at inhibiting its function to improve injury resolution have failed. Perhaps, better understanding of its beneficial roles in resolution of inflammation or its emerging function in tumorigenesis will spark new interest in revisiting the clinical value of ICAM‐1 as a potential therapeutic target.

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“…When switched to pathological high VEGF condition, the differential VE-cadherin mobility is lost and thus tip cell competition and stalk cell intercalation are disturbed [ 54 ]. In parallel, downstream of VEGF-induced ICAM1 expression and ROS production, Src kinase and protein tyrosine kinase 2 β are activated, both of which phosphorylate Y-658 on VE-cadherin for dissembling this protein [ 55 ]. Moreover, ICAM1 could also activate Rho GTPase for stress fiber formation, leading to permeability [ 55 ].…”

Section: Abnormal Angiogenesis In Diabetic Retinopathy and Nephropmentioning

confidence: 99%

Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

Zhang

Yuan

et al. 2016

Stem Cells International

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Despite being featured as metabolic disorder, diabetic patients are largely affected by hyperglycemia-induced vascular abnormality. Accumulated evidence has confirmed the beneficial effect of endothelial progenitor cells (EPCs) in coronary heart disease. However, antivascular endothelial growth factor (anti-VEGF) treatment is the main therapy for diabetic retinopathy and nephropathy, indicating the uncertain role of EPCs in the pathogenesis of diabetic microvascular disease. In this review, we first illustrate how hyperglycemia induces metabolic and epigenetic changes in EPCs, which exerts deleterious impact on their number and function. We then discuss how abnormal angiogenesis develops in eyes and kidneys under diabetes condition, focusing on “VEGF uncoupling with nitric oxide” and “competitive angiopoietin 1/angiopoietin 2” mechanisms that are shared in both organs. Next, we dissect the nature of EPCs in diabetic microvascular complications. After we overview the current EPCs-related strategies, we point out new EPCs-associated options for future exploration. Ultimately, we hope that this review would uncover the mysterious nature of EPCs in diabetic microvascular disease for therapeutics.

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Control of vascular permeability by adhesion molecules

Cited by 62 publications

References 134 publications

Activation of Vascular Endothelial Growth Factor (VEGF) Receptor 2 Mediates Endothelial Permeability Caused by Cyclic Stretch

Activation of Vascular Endothelial Growth Factor (VEGF) Receptor 2 Mediates Endothelial Permeability Caused by Cyclic Stretch

ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis

Endothelial Progenitor Cells in Diabetic Microvascular Complications: Friends or Foes?

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