Role of the Macrophage in the Regulation of Physiological and Pathological Angiogenesis

Transmembrane roundabout receptor family members (ROBO1–ROBO4) principally orchestrate the neuronal guidance mechanism of the nervous system. Secreted glycoprotein SLITs are the most appreciated ligands for ROBOs. Recently identified ROBO4 is the key mediator of SLIT-ROBO mediated developmental and pathological angiogenesis. Although SLIT2 has been shown to interact with ROBO4 as ligand, it remains an open question whether this protein is the physiologic partner of ROBO4. The purpose of this review is to summarise how reliable SLIT2 as ligand for ROBO4 is, if not what the other possible mechanisms demonstrated till date for ROBO4 mediated developmental and pathological angiogenesis are. We conclude that ROBO4 is expressed specially in vascular endothelial cells and maintains the vascular integrity via either SLIT2 dependent or SLIT2 independent manner. On the contrary, it promotes the pathological angiogenesis by involving different signalling arm(s)/unknown ligand(s). This review explores the interactions SLIT2/ROBO1, SLIT2/ROBO1–ROBO4, ROBO1/ROBO4, and ROBO4/UNC5B which can be promising and potential therapeutic targets for developmental angiogenesis defects and pathological angiogenesis. Finally we have reviewed the ROBO4 signalling pathways and made an effort to elaborate the insight of this signalling as therapeutic target of pathological angiogenesis.

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C6-ceramide treatment inhibits the proangiogenic activity of multiple myeloma exosomes via the miR-29b/Akt pathway

10.21203/rs.3.rs-18504/v1 ◽

2020 ◽

Author(s):

Liping Liu ◽

Qinmao Ye ◽

Langni Liu ◽

Ji Chen Bihl ◽

Yanfang Chen ◽

...

Keyword(s):

Multiple Myeloma ◽

Underlying Mechanism ◽

Tube Formation ◽

Akt Pathway ◽

Pathological Angiogenesis ◽

Protein Expressions ◽

Angiogenic Effect ◽

C6 Ceramide ◽

Rpmi 8226

Abstract Background: The increased bone marrow angiogenesis is involved in the progression of multiple myeloma (MM) with the underlying mechanism poorly understood. Cancer-released exosomes could play an important role in the pathological angiogenesis through exosomal microRNAs (miRs) delivery. MiR-29b has been reported in regulating the tumor angiogenesis. Methods: In this study, we explored the role of C6-ceramide (C6-cer, a Ceramide pathway activator) in the angiogenic effect of MM exosomes and its potential mechanism. MM cells (OPM2 and RPMI-8226) treated with C6-cer were studied for its effects on the endothelial cell (EC) functions . Results: Our results showed that exosomes released from MM cells treated by C6-cer ( Exo C6-cer ) significantly inhibited the proliferation, migration and tube formation of ECs. For mechanism studies, we found that the level of miR-29b was increased in ECs treated by exo C6-cer , while mRNA and protein expressions of Akt3, PI3K and VEGFA were decreased in ECs, indicating the involvement of Akt pathway. Furthermore, downregulation of miR-29b by inhibitor administration could prevent the exo C6-cer -induced cell proliferation, migration and angiogenesis of ECs, accompanied with the increased expressions of Akt3, PI3K and VEGFA. Conclusions: Collectively, our data suggest that exo C6-cer -mediated miR-29b expression participates in the progression of MM through suppressing the proliferation, migration and angiogenesis of ECs by targeting Akt signal pathway.

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Brain tumors: Regulation of angiogenesis.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e13540 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e13540-e13540 ◽

Cited By ~ 1

Author(s):

Eduard Evgenevich Rostorguev ◽

Elena Mikhaylovna Frantsiyants ◽

Yulia A. Pogorelova ◽

Natalia D. Cheryarina ◽

Larisa Kozlova ◽

...

Keyword(s):

Brain Tumors ◽

Test Results ◽

Metastatic Brain Tumors ◽

Metastatic Tissue ◽

Pathological Angiogenesis ◽

Important Mediator ◽

Student’S T ◽

G 14 ◽

Student’S T Test

e13540 Background: Cancer implicates pathological angiogenesis. The problem of treatment for primary and metastatic brain tumors is still unsolved. In addition to main angiogenic functions, VEGF family performs important mediator functions in the immune system. The role of VEGF family in central nervous system tumors is poorly studied. Our purpose was to study the levels of factors of angio- and lymphangiogenesis in tissues of glioblastomas (G), brain metastases (MTS), meningiomas and corresponding peritumoral area. Methods: Tissues of tumor and peritumoral zone (PZ) obtained during the surgery from 22 patients with G, 14 patients with brain MTS from breast cancer and 12 meningioma patients, mean age 39.2±4.8 years, were studied. Levels of VEGF-A, VEGFR-1, VEGF-C and VEGFR-3 were determined by ELISA. The data were processed using Statistica 10 program. The significance of differences was determined by Student's t-test. Results: VEGF-A levels in tissues of G and MTS were higher than in meningioma tissues by 74.7 and 94.5 times, respectively; levels of VEGF-R1 were 2.7 and 3.9 higher, and the VEGF-A/VEGF-R1 coefficient was 28.1 and 24.1 times higher, respectively. Levels of VEGF-C and VEGF-R3 were escalated only in G tissues compared to meningiomas (by 1.7 times on average). The VEGF-С/VEGF-R3 coefficient was similar in all studied tumors. VEGF-A levels were higher in PZ of G and MTS compared to PZ of meningiomas – by 78.2 and 110.7 times, respectively, while VEGF-R1 level was higher in G PZ only (by 5.5 times). The VEGF-A/VEGF-R1 coefficient was 14.5 and 128.5 times higher, respectively. VEGF-C level in PZ of G was escalated compared to meningiomas by 6.5 times, in MTS – by 1.6 times. VEGFR-3 contents did not differ significantly in all PZ samples, but the VEGF-С/VEGF-R3 coefficient was higher in PZ in G by 9 times and in MTS by 2 times. Conclusions: Compared to benign meningiomas, angio- and lymphangiogenesis are activated in glioblastoma tissue and angiogenesis – in metastatic tissue. Lymphangiogenesis is more active in peritumoral zone of glioblastomas compared to metastatic tissue, and angiogenesis is more active in peritumoral zone of metastases.

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Psoriasis and pathological angiogenesis: pathogenetic signifcance and therapeutic perspectives

Medical alphabet ◽

10.33667/2078-5631-2021-33-58-63 ◽

2021 ◽

pp. 58-63

Author(s):

O. A. Pritulo ◽

A. A. Petrov

Keyword(s):

Vascular Endothelial Growth Factor ◽

Inflammatory Process ◽

Vascular Endothelial ◽

Vascular Changes ◽

Pathological Angiogenesis ◽

Long Time ◽

Main Regulator ◽

Endothelial Growth Factor ◽

Cytokine Imbalance

The literature review presents data on the role of pathological angiogenesis in the development of psoriasis. Several recent studies have shown, in addition to cytokine imbalance and activation of the T-cell link of immunity, an important pathogenetic link is pathological vascularization. Vascular changes in the dermis appear before clinically visible skin manifestations and can persist for a long time after treatment, as well as the phenomena of neoangigenesis in the synovial membrane and enthesises contribute to the chronicization of inﬂammatory process in psoriatic arthritis. The article presents an overview of the modern literature on the main regulator of angiogenesis – vascular endothelial growth factor, its role in the pathogenesis of psoriasis and possible therapeutic prospects.

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0269 : Role of Frizzled7 during pathological angiogenesis: a model of retinopathy

Archives of Cardiovascular Diseases Supplements ◽

10.1016/s1878-6480(15)30041-0 ◽

2015 ◽

Vol 7 (2) ◽

pp. 146

Author(s):

Marie-Lise Bats ◽

Claire Peghaire ◽

Cécile Duplàa ◽

Thierry Couffinhal ◽

Pascale Dufourcq

Keyword(s):

Pathological Angiogenesis

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The Role of Complement in Angiogenesis

Antibodies ◽

10.3390/antib9040067 ◽

2020 ◽

Vol 9 (4) ◽

pp. 67

Author(s):

Maciej M. Markiewski ◽

Elizabeth Daugherity ◽

Britney Reese ◽

Magdalena Karbowniczek

Keyword(s):

Wound Healing ◽

Macular Degeneration ◽

Experimental Evidence ◽

Complement System ◽

Age Related Macular Degeneration ◽

New Developments ◽

Pathological Angiogenesis ◽

Age Related ◽

The Complement System

The link of the complement system to angiogenesis has remained circumstantial and speculative for several years. Perhaps the most clinically relevant example of possible involvement of complement in pathological neovascularization is age-related macular degeneration. Recent studies, however, provide more direct and experimental evidence that indeed the complement system regulates physiological and pathological angiogenesis in models of wound healing, retinal regeneration, age-related macular degeneration, and cancer. Interestingly, complement-dependent mechanisms involved in angiogenesis are very much context dependent, including anti- and proangiogenic functions. Here, we discuss these new developments that place complement among other important regulators of homeostatic and pathological angiogenesis, and we provide the perspective on how these newly discovered complement functions can be targeted for therapy.

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346 Role of GRK2 in Developing Vasculature and Pathological Angiogenesis

European Journal of Cancer ◽

10.1016/s0959-8049(12)71036-5 ◽

2012 ◽

Vol 48 ◽

pp. S84

Author(s):

V. Rivas ◽

R.M. Chapuli ◽

F. Mayor ◽

P. Penela

Keyword(s):

Pathological Angiogenesis

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Angiogenesis and Fibrogenesis in Oral Submucous Fibrosis: A Viewpoint

The Journal of Contemporary Dental Practice ◽

10.5005/jp-journals-10024-2244 ◽

2018 ◽

Vol 19 (2) ◽

pp. 242-245 ◽

Cited By ~ 1

Author(s):

Supriya M Kheur ◽

Sheetal S Choudhari ◽

Deepak G Kulkarni ◽

Sangeeta Patankar

Keyword(s):

Clinical Significance ◽

Oral Submucous Fibrosis ◽

Therapeutic Strategies ◽

Pathological Angiogenesis ◽

Prevention And Treatment ◽

New Strategy ◽

Submucous Fibrosis ◽

Fibrotic Disorders

ABSTRACT Oral submucous fibrosis (OSF) is characterized by excessive fibrosis of submucosa. The degree of vascularity in OSF has always been a matter of debate. Angiogenesis is the key mechanism involved in regeneration and repair. It also plays an important role in various pathologic conditions. Angiogenesis may contribute to the progression of fibrosis in fibrotic disorders. Inhibition of pathological angiogenesis is considered to be a new strategy for the treatment of various fibrotic disorders. In OSF, angiogenesis can be related to progression fibrosis. This article briefly describes the role of angiogenesis in pathogenesis of fibrosis in OSF and the importance of inhibition of pathologic angiogenesis in its prevention and treatment. Clinical significance Understanding the association between angiogenesis and fibrogenesis can help in developing new therapeutic strategies for treatment of OSF. How to cite this article Choudhari SS, Kulkarni DG, Patankar S, Kheur SM, Sarode SC, Sarode GS, Patil S. Angiogenesis and Fibrogenesis in Oral Submucous Fibrosis: A Viewpoint. J Contemp Dent Pract 2018;19(2):242-245.

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Endothelial cell polarity and extracellular matrix production rely on functional ATP6AP2 during developmental and pathological angiogenesis

10.1101/2021.08.16.456486 ◽

2021 ◽

Author(s):

NR Patel ◽

A Blanks ◽

Y Li ◽

MC Prieto ◽

SM Meadows

Keyword(s):

Extracellular Matrix ◽

Cell Migration ◽

Endothelial Cell ◽

Cell Polarity ◽

Transmembrane Protein ◽

Critical Role ◽

Matrix Composition ◽

Pathological Angiogenesis ◽

Extracellular Matrix Components

AbstractThe (Pro)renin receptor ((P)RR), also known as ATP6AP2, is a single-transmembrane protein that is implicated in a multitude of biological processes. However, the exact role of ATP6AP2 during blood vessel development remains largely undefined. Here, we use an inducible endothelial cell (EC)-specific Atp6ap2 knockout mouse model to investigate the role of ATP6AP2 during both physiological and pathological angiogenesis in vivo. We observed that postnatal deletion of Atp6ap2 in ECs results in cell migration defects, loss of tip cell polarity and subsequent impairment of retinal angiogenesis. In vitro, Atp6ap2 deficient ECs similarly displayed reduced cell migration, impaired sprouting, and defective cell polarity. Transcriptional profiling of ECs isolated from Atp6ap2 mutant mice further indicated regulatory roles in angiogenesis, cell migration and extracellular matrix composition. Mechanistically, we showed that expression of various extracellular matrix components is controlled by ATP6AP2 via the extracellular-signal-regulated kinase (ERK) pathway. Furthermore, Atp6ap2 deficient retinas exhibited reduced revascularization in an oxygen induced retinopathy model. Collectively, our results demonstrated a critical role of ATP6AP2 as a regulator of developmental and pathological angiogenesis.

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