Flow‐dependent regulation of angiopoietin‐2

Göettsch, Winfried; Gryczka, Corina; Korff, Thomas; Ernst, E.; Goettsch, Claudia; Seebach, Jochen; Schnittler, Hans; Augustin, Hellmut G.; Morawietz, Henning

doi:10.1002/jcp.21229

Cited by 91 publications

(70 citation statements)

References 59 publications

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“…Interestingly, ANG-2 is also regulated by mechanical shear-stress on ECs. FoxO1 and KLF2 have been shown to play a role in mediating ANG-2 regulation by shear-stress in different ways 40,41 . Considering the recent finding that YAP plays a key role in cellular mechanotransduction, it is not surprising that ANG-2 is regulated by YAP in ECs.…”

Section: Discussionmentioning

confidence: 99%

Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2

et al. 2015

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Angiogenesis is regulated by the dynamic interaction between endothelial cells (ECs).Hippo-Yes-associated protein (YAP) signalling has emerged as a key pathway that controls organ size and tissue growth by mediating cell contact inhibition. However, the role of YAP in EC has not been defined yet. Here, we show expression of YAP in the developing front of mouse retinal vessels. YAP subcellular localization, phosphorylation and activity are regulated by VE-cadherin-mediated-EC contacts. This VE-cadherin-dependent YAP phosphorylation requires phosphoinositide 3-kinase-Akt activation. We further identify angiopoietin-2 (ANG-2) as a potential transcriptional target of YAP in regulating angiogenic activity of EC in vitro and in vivo. Overexpression of YAP-active form in EC enhances angiogenic sprouting, and this effect is blocked by ANG-2 depletion or soluble Tie-2 treatment. These findings implicate YAP as a critical regulator in angiogenesis and provide new insights into the mechanism coordinating junctional stability and angiogenic activation of ECs.

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Section: Discussionmentioning

confidence: 99%

Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2

et al. 2015

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“…FACS analysis showed that Ang-1 binding was unaffected by pan-integrin inhibitor EDTA, suggesting that Ang-1 fails to interact with monocyte integrins. More recently, low-shear flow conditions were identified to increase the expression of Ang-2 in human endothelial cells, 22 and Ang-2 potentiates TNF-␣-induced monocyte adhesion. 23 In FACS-based binding, we show that Ang-1, but not Ang-2, binds to monocytes, whereas both Ang-1 and Ang-2 bind to HUVECs.…”

Section: Discussionmentioning

confidence: 99%

Angiopoietin-1 Induces Migration of Monocytes in a Tie-2 and Integrin-Independent Manner

et al. 2010

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Abstract-Angiopoietin-1 (Ang-1) is an angiogenic growth factor that activates Tie-2 and integrins to promote vessel wall remodeling. The recent finding of the potential proatherogenic effects of Ang-1 prompted us to investigate whether Ang-1 promotes monocyte chemotaxis, endothelial binding, and transendothelial migration, key events in the progression of atherosclerosis. Here, we show that Ang-1 induces chemotaxis of monocytes in a manner that is independent of Tie-2 and integrin binding but dependent on phosphoinositide 3-kinase and heparin. In addition, Ang-1 promoted phosphoinositide 3-kinase-dependent binding of monocytes to endothelial monolayers and stimulated transendothelial migration. Fluorescence-activated cell sorting analysis showed that exogenous Ang-1 adheres directly to monocytes as well as to human umbilical endothelial cells, but neither Tie-2 mRNA nor protein were expressed by primary monocytes. Although Ang-1 binding to human umbilical endothelial cells was partially Tie-2 and integrin dependent, Ang-1 binding to monocytes was independent of these factors. Finally, preincubation of monocytes with soluble heparin abrogated Ang-1 binding to monocytes and migration, and partially prevented Ang-1 binding to human umbilical endothelial cells. In summary, Ang-1 induces chemotaxis of monocytes by a mechanism that is dependent on phosphoinositide 3-kinase and heparin but independent of Tie-2 and integrins. The ability of Ang-1 to recruit monocytes suggests it may play a role in inflammatory angiogenesis and may promote atherosclerosis. (Hypertension. 2010;56:477-483.)

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“…Studies in cultured ECs revealed that laminar flow prompts PI3K-AKTdependent inactivation of FOXO1. 68,69,70 AMPK has also been implicated in flow-mediated inhibition of FOXO1. 68 Whether this inhibitory effect requires the direct phosphorylation of FOXO1 by AMPK must be determined.…”

Section: Foxos and Sirtuins In Vascular Maintenance And Homeostasismentioning

confidence: 99%

FOXOs and Sirtuins in Vascular Growth, Maintenance, and Aging

Oellerich

Potente

2012

Circulation Research

136

128

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Flow‐dependent regulation of angiopoietin‐2

Cited by 91 publications

References 59 publications

Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2

Yes-associated protein regulates endothelial cell contact-mediated expression of angiopoietin-2

Angiopoietin-1 Induces Migration of Monocytes in a Tie-2 and Integrin-Independent Manner

FOXOs and Sirtuins in Vascular Growth, Maintenance, and Aging

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