Angiopoietins in angiogenesis and beyond

Tsigkos, Stelios; Koutsilieris, Micheal; Papapetropoulos, Andreas

doi:10.1517/eoid.12.6.933.21790

Cited by 12 publications

(13 citation statements)

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“…To further study the mechanism of C‐18 action, we incubated cells with either Ang‐1 or VEGF and tested the ability of the sulindac analogue to inhibit activation of cascades relevant to angiogenesis. In line with previous reports, both growth factors stimulated ERK1/2 and p38 mitogen‐activated protein kinase (MAPK) phosphorylation, as well as Akt activation (Jones et al , 2001; Harfouche et al , 2003; Tsigkos et al , 2003). C‐18 inhibited activation of all three pathways tested.…”

Section: Discussionsupporting

confidence: 92%

Anti‐angiogenic properties of a sulindac analogue

Pyriochou

Tsigkos

Vassilakopoulos

et al. 2007

British J Pharmacology

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Background and purpose: Angiopoietins (Ang) are crucial for new blood vessel formation and exert their effects by acting on the Tie2 receptor. We have recently described a sulindac analogue 2-((1E,Z)-1-benzylidene-5-bromo-2-methyl-1H-inden-3-yl)acetic acid; termed C-18 from now onwards) that inhibits Tie2 receptor activity in kinase assays in vitro. Here, we have assessed the ability of C-18 to inhibit angiogenesis-related properties of endothelial cells and tested its selectivity for the Tie2 receptor. Experimental approach: For in vitro experiments human umbilical vein endothelial cells (HUVEC) were used. Proliferation was measured using the MTT assay; migration assays were performed in a modified Boyden chamber and tube-like structure formation was determined on matrigel. The effects of C-18 in vivo were evaluated in the chicken chorioallantoic membrane (CAM). Key results: Pre-treatment of HUVEC with C-18 blocked Ang-1-stimulated migration, but also abolished vascular endothelial cell growth factor (VEGF)-and fibroblast growth factor 2-induced responses. Incubation with C-18 inhibited serum-induced proliferation in a concentration-dependent manner; C-18 was, however, without effect on Ang-1-induced survival. In addition, we observed that C-18 did not inhibit ligand-induced receptor phosphorylation of Tie2 or VEGFR2. On the other hand, C-18 blocked activation of members of the mitogen-activated protein kinase family and of the Ser/Thr kinase Akt induced by both VEGF and Ang-1. Furthermore, incubation of CAMs with C-18 led to a dose-dependent inhibition of vascular length. Conclusions and implications: C-18 did not act as a Tie2 inhibitor, as originally thought, but rather inhibited growth factorstimulated signalling pathways that regulate endothelial cell migration and potently reduces neovascularization in vivo.

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Section: Discussionsupporting

confidence: 92%

Anti‐angiogenic properties of a sulindac analogue

Pyriochou

Tsigkos

Vassilakopoulos

et al. 2007

British J Pharmacology

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“…This is in keeping with previous studies demonstrating abnormalities in markers of angiogenesis in hypertension [1, 4]. VEGF, Ang‐1 and Ang‐2 are important regulators of angiogenesis; they, in turn, are regulated by a number of factors including hypoxia and markers of inflammation [6, 18]. It is likely that in hypertension, which is associated with rarefaction of the microcirculation, these factors are increased as a compensatory mechanism for the relative hypoxia that this rarefied microcirculation may cause [19].…”

Section: Discussionsupporting

confidence: 86%

“…However, the role of these markers in the pathogenesis of TOD is unclear. Increasingly, newer angiogenic markers such as angiopoietin 1 and 2 (Ang‐1 and Ang‐2) and the soluble angiopoietin receptor Tie‐2 have also been postulated as having a role in the process of angiogenesis [6]. Nonetheless, the role of the angiopoietin/Tie‐2 system in hypertension has not been previously studied.…”

Section: Introductionmentioning

confidence: 99%

“…This study was designed to test the hypotheses regarding VEGF, angiopoietins and platelets in hypertension and TOD. We first hypothesized that there would be, like raised VEGF [5, 6], raised plasma Ang‐1, Ang‐2 and Tie‐2 in hypertension. We also hypothesized that levels would be greater in patients whose hypertension was compounded by TOD such as stroke.…”

Section: Introductionmentioning

confidence: 99%

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Abnormal angiopoietins 1&2, angiopoietin receptor Tie‐2 and vascular endothelial growth factor levels in hypertension: relationship to target organ damage [a sub‐study of the Anglo‐Scandinavian Cardiac Outcomes Trial (ASCOT)]

Nadar

Blann

Beevers

et al. 2005

Journal of Internal Medicine

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Abstract. Nadar SK, Blann A, Beevers DG, Lip GYH (City Hospital, Birmingham, UK). Abnormal angiopoietins 1&2, angiopoietin receptor Tie-2 and vascular endothelial growth factor levels in hypertension: relationship to target organ damage [a sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)]. J Intern Med 2005; 258: 336-343.Background. The increased risk of target organ damage (TOD) in hypertension may be related to a prothrombotic or hypercoagulable state, with abnormalities in platelet activation. Altered angiogenesis, possibly related to increased plasma vascular endothelial growth factor (VEGF) is also a feature of hypertension. We hypothesized a link between altered angiogenesis and TOD in hypertension. Accordingly, the angiogenic growth factors VEGF, angiopoietin 1 and 2 (Ang 1 & 2) and soluble angiopoietin receptor Tie-2 in plasma and in platelets were assessed in terms of the presence or absence of hypertensive TOD. Methods. We studied 199 patients (75% men; mean age 68 years) with hypertension. Of these, 125 had evidence of hypertensive TOD (stroke, previous myocardial infarction, angina, left ventricular hypertrophy and mild renal failure). Patients were

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“…The two major members of the angiopoietin family are angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) [108]. Tie2 is the main signalling receptor and binds both Ang1 and Ang2, although in most circumstances only Ang1 induces receptor phosphorylation [109][110][111]. Ang2 predominantly antagonises Ang1-induced phosphorylation of Tie2 [110].…”

Section: Glomerular Vascular Endothelial Growth Factors (Vegf)mentioning

confidence: 99%

Endothelial glycocalyx restoration by growth factors in diabetic nephropathy

Desideri

Onions

Baker

et al. 2019

BIR

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The endothelial glycocalyx (eGlx) constitutes the first barrier to protein in all blood vessels. This is particularly noteworthy in the renal glomerulus, an ultrafiltration barrier. Leakage of protein, such as albumin, across glomerular capillaries results in albumin in the urine (albuminuria). This is a hall mark of kidney disease and can reflect loss of blood vessel integrity in microvascular beds elsewhere. We discuss evidence demonstrating that targeted damage to the glomerular eGlx results in increased glomerular albumin permeability. EGlx is lost in diabetes and experimental models demonstrate loss from glomerular endothelial cells. Vascular endothelial growth factor (VEGF)A is upregulated in early diabetes, which is associated with albuminuria. Treatment with paracrine growth factors such as VEGFC, VEGF165b and angiopoietin-1 can modify VEGFA signalling, rescue albumin permeability and restore glomerular eGlx in models of diabetes. Manipulation of VEGF receptor 2 signalling, or a common eGlx biosynthesis pathway by these growth factors, may protect and restore the eGlx layer. This would help to direct future therapeutics in diabetic nephropathy.

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Angiopoietins in angiogenesis and beyond

Cited by 12 publications

References 0 publications

Anti‐angiogenic properties of a sulindac analogue

Anti‐angiogenic properties of a sulindac analogue

Abnormal angiopoietins 1&2, angiopoietin receptor Tie‐2 and vascular endothelial growth factor levels in hypertension: relationship to target organ damage [a sub‐study of the Anglo‐Scandinavian Cardiac Outcomes Trial (ASCOT)]

Endothelial glycocalyx restoration by growth factors in diabetic nephropathy

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