The role of Hippo/yes‐associated protein signalling in vascular remodelling associated with cardiovascular disease

He, Jinlong; Bao, Qiankun; Meng, Yan; Liang, Jing; Zhu, Yi; Wang, Chunjiong; Ai, Ding

doi:10.1111/bph.13806

Cited by 87 publications

(78 citation statements)

References 70 publications

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“…For instance, sphingosine-1-phosphate [S1P activates the S1P receptor, which in turn activates Rac], increases the formation of junction protrusions (both JAIL and lamellipodia) and improves barrier function (Mehta et al, 2005;Tauseef et al, 2008;Breslin et al, 2015;Cao et al, 2017). Furthermore, signaling through YAP/TAZ proteins (Totaro et al, 2018), the transcriptional co-activators of the Hippo signaling pathway involved in growth control and in cardiovascular development and diseases (Huang et al, 2005;He et al, 2018;Park and Kwon, 2018), has been demonstrated to be important in this process, as YAP/TAZ depletion reduced the formation of JAIL (Giampietro et al, 2015;Neto et al, 2018). It is reasonable to assume that signals that modulate the organization and dynamics of EC junctions, such as the vascular phosphotyrosine phosphatase (VE-PTP; also known as PTPRB), which binds to VE-cadherin and thus might be able to control VE-cadherin cluster formation through phosphorylation (Nawroth et al, 2002;Hayashi et al, 2013), VEGFR1 (Cao, 2009) and Angiopoetin-Tie signaling, 1) Decrease in Rel-VEcad-C 2) VE-cadherin cluster can be arranged and distributed as: -linear (Rel-VEcad-C can be low or high) -interrupted -reticular -as plaques (result of JAIL) -as membrane invaginations (?…”

Section: Molecular Control Of Jailmentioning

confidence: 99%

Putting VE-cadherin into JAIL for junction remodeling

Cao

Schnittler

2019

Journal of Cell Science

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Junction dynamics of endothelial cells are based on the integration of signal transduction, cytoskeletal remodeling and contraction, which are necessary for the formation and maintenance of monolayer integrity, but also enable repair and regeneration. The VE-cadherincatenin complex forms the molecular basis of the adherence junctions and cooperates closely with actin filaments. Several groups have recently described small actin-driven protrusions at the cell junctions that are controlled by the Arp2/3 complex, contributing to cell junction regulation. We identified these protrusions as the driving force for VE-cadherin dynamics, as they directly induce new VE-cadherin-mediated adhesion sites, and have accordingly referred to these structures as junction-associated intermittent lamellipodia (JAIL). JAIL extend over only a few microns and thus provide the basis for a subcellular regulation of adhesion. The local (subcellular) VE-cadherin concentration and JAIL formation are directly interdependent, which enables autoregulation. Therefore, this mechanism can contribute a subcellularly regulated adaptation of cell contact dynamics, and is therefore of great importance for monolayer integrity and relative cell migration during wound healing and angiogenesis, as well as for inflammatory responses. In this Review, we discuss the mechanisms and functions underlying these actin-driven protrusions and consider their contribution to the dynamic regulation of endothelial cell junctions.

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Section: Molecular Control Of Jailmentioning

confidence: 99%

Putting VE-cadherin into JAIL for junction remodeling

Cao

Schnittler

2019

Journal of Cell Science

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“…Angioplasty is a highly effective treatment for narrowing of the coronary arteries. However, restenosis after angioplasty, the healing response of the arterial wall to mechanical injury, greatly dampens the satisfactory prognosis of atherosclerosis (He et al, ; Liu, Bauer, & Martin, ). The main pathogenesis of restenosis is neointimal hyperplasia and vessel remodelling.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of polycomb repressor complex 2 ameliorates neointimal hyperplasia by suppressing trimethylation of H3K27 in vascular smooth muscle cells

Liang

Cai

et al. 2019

British J Pharmacology

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Background and Purpose The increased proliferation and migration of vascular smooth muscle cells (VSMCs) after arterial injury contributes greatly to the pathogenesis of neointimal hyperplasia. As a major component of epigenetics, histone methylation plays an important role in several cardiovascular diseases. However, its role in restenosis is still unclear. Experimental Approach Human aortic VSMCs were challenged with PDGF‐BB, and total histones were extracted and analysed by HPLC/MS. For the in vivo study, rats were subjected to wire‐guided common carotid injury. Key Results PDGF‐BB markedly increased the H3K27me3 level, as demonstrated by use of HPLC/MS and confirmed by western blot analysis. Enhancer of zeste homologue 2 (EZH2), the histone H3K27 methyltransferase component of polycomb repressive complex 2, was also up‐regulated by PDGF‐BB in VSMCs, and in the neointimal hyperplasia induced by wire injury of the rat carotid artery. Furthermore, inhibiting H3K27me3 by treatment with 3‐μM UNC1999, an EZH2/1 inhibitor, significantly suppressed PDGF‐BB‐induced VSMC proliferation compared with the PDGF‐BB‐treated group. Consistently, neointimal formation was significantly attenuated by oral or perivascular administration of UNC1999 compared with the sham group. Mechanistically, the increase in H3K27me3 inhibited the transcription of the cyclin‐dependent kinase inhibitor p16INK4A and thus promoted VSMC proliferation. Conclusions and Implications Vascular injury elevated the expression of EZH2 and the downstream target H3K27me3, which suppressed p16INK4A expression in VSMCs and promoted VSMC proliferation and neointimal hyperplasia. EZH2 inhibition might be a potential therapeutic target for restenosis.

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“…Activation of endothelial cells, such as proliferation, migration, invasion, and the tube formation are the hallmarks of angiogenesis. Previous studies demonstrated Hippo/YAP signaling is critical in regulating EC survival, proliferation and migration [9,10]. Activation of YAP caused by activation of VE-cadherin, PI3K/Akt signaling, and actin-binding protein EPS8 results in tubular network formation [7,11].…”

Section: Introductionmentioning

confidence: 98%

YAP Overexpression in Breast Cancer Cells Promotes Angiogenesis Through Activating Yap Signaling in Vascular Endothelial Cells

Yoshida

Song

Yao

et al. 2020

Preprint

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Background:The YAP signaling pathway is altered and implicated as oncogenic in human mammary cancers.However, roles of YAP signaling that regulate the breast tumor angiogenesis have remained elusive. Tumor angiogenesis is coordinated by the activation of both cancer cells and vascular endothelial cells. Whether the YAP signalingpathway can regulate the intercellular interaction between cancer cells and endothelial cellsis essentially unknown.Results: We showed here that conditioned media from YAP overexpressed breast cancer cells (CM-YAP+) could promote angiogenesis, accompanied byincreased tube formation, migration, and proliferation of human umbilical vein endothelial cells (HUVECs). Down regulation of YAP in HUVECs reversed CM-YAP+ induced angiogenesis.CM-YAP+ time-dependently activated YAP inHUVECs by dephosphorylating YAP and increasing nuclear translocation.We also identified that both G13-RhoA and PI3K/Akt signaling pathway were necessary for CM-YAP+ induced activation of YAP.Besides, connective tissue growth factor (CTGF) and angiopoietin-2 (ANG-2)actedas down-stream of YAP in HUVECs to promote angiogenesis.In addition, subcutaneous tumors nude mice model demonstrated that tumors overexpressed YAP revealed moreneovascularization in vivo.Conclusions: YAP-YAP interaction between breastcancer cells and endothelial cellscould promote tumor angiogenesis, supporting that YAP is a potential marker and target fordeveloping novel therapeutic strategies against breast cancer.

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The role of Hippo/yes‐associated protein signalling in vascular remodelling associated with cardiovascular disease

Abstract: This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc.

Cited by 87 publications

References 70 publications

Putting VE-cadherin into JAIL for junction remodeling

Putting VE-cadherin into JAIL for junction remodeling

Inhibition of polycomb repressor complex 2 ameliorates neointimal hyperplasia by suppressing trimethylation of H3K27 in vascular smooth muscle cells

YAP Overexpression in Breast Cancer Cells Promotes Angiogenesis Through Activating Yap Signaling in Vascular Endothelial Cells

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