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Cells
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Angiopoietin Signaling
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Angiopoietin Signaling

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling".

Deadline for manuscript submissions: closed (1 October 2020) | Viewed by 24498

Special Issue Editor

Prof. Dr. Sabah Hussain

E-Mail Website
Guest Editor
Department of Medicine, Division of Experimental Medicine, McGill University Health Centre, Montreal, QC, Canada
Interests: vascular biology; angiogenesis; cell signaling; angiopoietins; tyrosine kinase receptors; endothelium; cell proliferation; cell differentiation; micro-RNAs; long noncoding RNAs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The endothelium plays critical roles in cardiovascular homeostasis and remodelling, including the control of permeability and vascular tone, proliferation and growth of smooth muscle cells, adhesion of leukocytes, thrombosis, and coagulation. The angiopoietin-1 (Ang-1)/Tie-2 receptor pathway is one of the most important regulators of these processes. Along with the vascular endothelial growth factor (VEGF) pathway, the Ang-1/Tie-2 axis plays an essential and complementary role in vessel formation during embryogenesis. While both promote angiogenesis, only Ang-1 promotes maturation of blood vessels and protects against vascular inflammation. Further to these physiological roles in regulating vascular homeostasis within the vascular and lymphatic systems, the Ang-1/Tie-2 axis also plays critical defensive roles against diseases such as diabetes, sepsis, and atherosclerosis and is a major factor in many ocular diseases, and blindness. This Special Issue offers an open access forum that aims to bring together a collection of original research and review articles addressing the expanding fields of angiopoietin biology and signaling. We hope to provide an important resource for understanding the molecular mechanisms involved in angiopoietin biology and for the exploration of therapeutic potentials of angiopoietins in various diseases. Suggested potential topics may be: regulation of inflammatory processes by angiopoietins; epigenetic mechanisms of angiopoietin signaling; angiopoietins and cancer angiogenesis; extracellular microvesicles and angiopoietin biology; therapeutic potentials of angiopoietins; vascular and extravascular biological functions of angiopoietin-2; and regulation of cell metabolism by angiopoietins.

Prof. Sabah Hussain
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • angiopoietins
  • angiogenesis
  • inflammation
  • cell signaling
  • micro-RNAs
  • exosomes
  • cell metabolism
  • tyrosine kinase receptors
  • cancer angiogenesis

Published Papers (6 papers)

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Research

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18 pages, 3063 KiB  
Article
Roles of miR-640 and Zinc Finger Protein 91 (ZFP91) in Angiopoietin-1-Induced In Vitro Angiogenesis
by Sharon Harel, Veronica Sanchez-Gonzalez, Raquel Echavarria, Dominique Mayaki and Sabah NA Hussain
Cells 2020, 9(7), 1602; https://doi.org/10.3390/cells9071602 - 02 Jul 2020
Cited by 11 | Viewed by 2595
Abstract
Angiopoietin-1 (Ang-1) is a ligand of Tie-2 receptors that promotes angiogenesis. It has been established that regulatory loops exist between angiogenic growth factors and distinct pro or anti-angiogenic miRNAs, but the nature and the roles of Ang-1-regulated miRNAs remain unclear. In this study, [...] Read more.
Angiopoietin-1 (Ang-1) is a ligand of Tie-2 receptors that promotes angiogenesis. It has been established that regulatory loops exist between angiogenic growth factors and distinct pro or anti-angiogenic miRNAs, but the nature and the roles of Ang-1-regulated miRNAs remain unclear. In this study, we assessed the role of miR-640 in Ang-1-induced angiogenesis in human umbilical vein endothelial cells (HUVECs). Exposure to Ang-1 (300 ng/mL) from 6 to 72 h significantly decreased expression of mature miR-640, a response that was mediated by Tie-2 receptors and was also observed in response to Ang-2, the vascular endothelial growth factor, and transforming growth factor β. Increasing miR-640 levels using a mimic inhibited Ang-1-induced cell migration and capillary-like tube formation whereas inhibition of miR-640 enhanced these responses. Pull down assays of biotinylated miR-640 revealed that miR-640 directly targets Zinc Finger Protein 91 (ZFP91), an atypical E3-ubiquitin ligase. Ang-1 exposure induced ZFP91 expression through down-regulation of miR-640. Silencing of ZFP91 significantly inhibited Ang-1-induced cell migration and tube formation. We conclude that Ang-1 upregulates ZFP91 expression through transcriptional down-regulation of miR-640 and that ZFP91 plays important roles in the promotion of Ang-1-induced endothelial cell migration and differentiation. Full article
(This article belongs to the Special Issue Angiopoietin Signaling)
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15 pages, 4587 KiB  
Article
Rap1 Is Involved in Angiopoietin-1-Induced Cell-Cell Junction Stabilization and Endothelial Cell Sprouting
by Vanda Gaonac’h-Lovejoy, Cécile Boscher, Chantal Delisle and Jean-Philippe Gratton
Cells 2020, 9(1), 155; https://doi.org/10.3390/cells9010155 - 08 Jan 2020
Cited by 14 | Viewed by 3688
Abstract
Angiopoietin-1 (Ang-1) is an important proangiogenic factor also involved in the maintenance of endothelial-barrier integrity. The small GTPase Rap1 is involved in the regulation of adherens junctions through VE-cadherin-mediated adhesion, and in endothelial permeability. While many studies established that Rap1 activation is critical [...] Read more.
Angiopoietin-1 (Ang-1) is an important proangiogenic factor also involved in the maintenance of endothelial-barrier integrity. The small GTPase Rap1 is involved in the regulation of adherens junctions through VE-cadherin-mediated adhesion, and in endothelial permeability. While many studies established that Rap1 activation is critical for endothelial cell–cell adhesions, its roles in the antipermeability effects of Ang-1 are ill-defined. Thus, we determined the contribution of Rap1 to Ang-1-stimulated angiogenic effects on endothelial cells (ECs). We found that Rap1 is activated following Ang-1 stimulation and is required for the antipermeability effects of Ang-1 on EC monolayers. Our results also revealed that Rap1 is necessary for EC sprouting stimulated by Ang-1 but had no significant effect on Ang-1-induced EC migration and adhesion. In contrast, downregulation of VE-cadherin markedly increased the adhesiveness of ECs to the substratum, which resulted in inhibition of Ang-1-stimulated migration. These results revealed that Rap1 is central to the effects of Ang-1 at intercellular junctions of ECs, whereas VE-cadherin is also involved in the adhesion of ECs to the extracellular matrix. Full article
(This article belongs to the Special Issue Angiopoietin Signaling)
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Review

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15 pages, 1391 KiB  
Review
Insight into the Role of Angiopoietins in Ageing-Associated Diseases
by Shin-ichiro Hayashi, Hiromi Rakugi and Ryuichi Morishita
Cells 2020, 9(12), 2636; https://doi.org/10.3390/cells9122636 - 08 Dec 2020
Cited by 19 | Viewed by 3489
Abstract
Angiopoietin (Ang) and its receptor, TIE signaling, contribute to the development and maturation of embryonic vasculature as well as vascular remodeling and permeability in adult tissues. Targeting both this signaling pathway and the major pathway with vascular endothelial growth factor (VEGF) is expected [...] Read more.
Angiopoietin (Ang) and its receptor, TIE signaling, contribute to the development and maturation of embryonic vasculature as well as vascular remodeling and permeability in adult tissues. Targeting both this signaling pathway and the major pathway with vascular endothelial growth factor (VEGF) is expected to permit clinical applications, especially in antiangiogenic therapies against tumors. Several drugs targeting the Ang-TIE signaling pathway in cancer patients are under clinical development. Similar to how cancer increases with age, unsuitable angiogenesis or endothelial dysfunction is often seen in other ageing-associated diseases (AADs) such as atherosclerosis, Alzheimer’s disease, type 2 diabetes, chronic kidney disease and cardiovascular diseases. Thus, the Ang-TIE pathway is a possible molecular target for AAD therapy. In this review, we focus on the potential role of the Ang-TIE signaling pathway in AADs, especially non-cancer-related AADs. We also suggest translational insights and future clinical applications of this pathway in those AADs. Full article
(This article belongs to the Special Issue Angiopoietin Signaling)
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16 pages, 678 KiB  
Review
The Angiopoietin/Tie2 Pathway in Hepatocellular Carcinoma
by Bart Vanderborght, Sander Lefere, Hans Van Vlierberghe and Lindsey Devisscher
Cells 2020, 9(11), 2382; https://doi.org/10.3390/cells9112382 - 30 Oct 2020
Cited by 21 | Viewed by 4011
Abstract
Due to the usually late diagnosis and lack of effective therapies, hepatocellular carcinoma (HCC), which poses a growing global health problem, is characterized by a poor prognosis. Angiogenesis plays an important role in HCC progression, and vascular endothelial growth factor (VEGF) and angiopoietins [...] Read more.
Due to the usually late diagnosis and lack of effective therapies, hepatocellular carcinoma (HCC), which poses a growing global health problem, is characterized by a poor prognosis. Angiogenesis plays an important role in HCC progression, and vascular endothelial growth factor (VEGF) and angiopoietins (Angs) are key drivers of HCC angiogenesis. VEGF-targeting strategies already represent an important component of today’s systemic treatment landscape of HCC, whereas targeting the Ang/Tie2 signaling pathway may harbor future potential in this context due to reported beneficial anticancer effects when targeting this pathway. In addition, a better understanding of the relation between Angs and HCC angiogenesis and progression may reveal their potential as predictive factors for post-treatment disease progression and prognosis. In this review, we give a comprehensive overview of the complex role of Ang/Tie2 signaling in HCC, pinpointing its potential value as biomarker and target for HCC treatments, aiding HCC diagnosis and therapy. Full article
(This article belongs to the Special Issue Angiopoietin Signaling)
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14 pages, 288 KiB  
Review
Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab
by Majid Khan, Aamir A. Aziz, Noah A. Shafi, Tayeb Abbas and Arshad M. Khanani
Cells 2020, 9(8), 1869; https://doi.org/10.3390/cells9081869 - 10 Aug 2020
Cited by 64 | Viewed by 6409
Abstract
This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is [...] Read more.
This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is upregulated, deactivating Tie-2, resulting in vascular leakage, pericyte loss, and inflammation. Recombinant Angiopeotin-1 (Ang-1), Ang-2-blocking molecules, and inhibitors of vascular endothelial protein tyrosine phosphatase (VE-PTP) decrease inflammation-associated vascular leakage, showing therapeutic effects in diabetes, atherosclerosis, and ocular neovascular diseases. In addition, novel studies show that angiopoietin-like proteins may play an important role in cellular metabolism leading to retinal vascular diseases. Current therapeutic focus combines Ang-Tie targeted drugs with other anti-angiogenic or immune therapies. Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema. Phase 2 results have produced promising outcomes with regard to efficacy and durability. Faricimab is currently being evaluated in global Phase 3 studies. Full article
(This article belongs to the Special Issue Angiopoietin Signaling)
17 pages, 982 KiB  
Review
Role of Angiopoietins in Development of Cancer and Neoplasia Associated with Viral Infection
by Xiaolan Yu and Fengchun Ye
Cells 2020, 9(2), 457; https://doi.org/10.3390/cells9020457 - 18 Feb 2020
Cited by 31 | Viewed by 3763
Abstract
Angiopoietin/tyrosine protein kinase receptor Tie-2 signaling in endothelial cells plays an essential role in angiogenesis and wound healing. Angiopoietin-1 (Ang-1) is crucial for blood vessel maturation while angiopoietin-2 (Ang-2), in collaboration with vascular endothelial growth factor (VEGF), initiates angiogenesis by destabilizing existing blood [...] Read more.
Angiopoietin/tyrosine protein kinase receptor Tie-2 signaling in endothelial cells plays an essential role in angiogenesis and wound healing. Angiopoietin-1 (Ang-1) is crucial for blood vessel maturation while angiopoietin-2 (Ang-2), in collaboration with vascular endothelial growth factor (VEGF), initiates angiogenesis by destabilizing existing blood vessels. In healthy people, the Ang-1 level is sustained while Ang-2 expression is restricted. In cancer patients, Ang-2 level is elevated, which correlates with poor prognosis. Ang-2 not only drives tumor angiogenesis but also attracts infiltration of myeloid cells. The latter rapidly differentiate into tumor stromal cells that foster tumor angiogenesis and progression, and weaken the host’s anti-tumor immunity. Moreover, through integrin signaling, Ang-2 induces expression of matrix metallopeptidases (MMPs) to promote tumor cell invasion and metastasis. Many oncogenic viruses induce expression of Ang-2 to promote development of neoplasia associated with viral infection. Multiple Ang-2 inhibitors exhibit remarkable anti-tumor activities, further highlighting the importance of Ang-2 in cancer development. Full article
(This article belongs to the Special Issue Angiopoietin Signaling)
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