RESVEGA, by the presence of Resveratrol, inhibits retinal endothelial tube formation

AbstractLewis Y Ag (LeY) is a cell-surface tetrasaccharide that participates in angiogenesis. Recently, we demonstrated that LeY is a specific ligand of the recombinant lectin-like domain of thrombomodulin (TM). However, the biologic function of interaction between LeY and TM in endothelial cells has never been investigated. Therefore, the role of LeY in tube formation and the role of the recombinant lectin-like domain of TM—TM domain 1 (rTMD1)—in antiangiogenesis were investigated. The recombinant TM ectodomain exhibited lower angiogenic activity than did the recombinant TM domains 2 and 3. rTMD1 interacted with soluble LeY and membrane-bound LeY and inhibited soluble LeY-mediated chemotaxis of endothelial cells. LeY was highly expressed on membrane ruffles and protrusions during tube formation on Matrigel. Blockade of LeY with rTMD1 or Ab against LeY inhibited endothelial tube formation in vitro. Epidermal growth factor (EGF) receptor in HUVECs was LeY modified. rTMD1 inhibited EGF receptor signaling, chemotaxis, and tube formation in vitro, and EGF-mediated angiogenesis and tumor angiogenesis in vivo. We concluded that LeY is involved in vascular endothelial tube formation and rTMD1 inhibits angiogenesis via interaction with LeY. Administration of rTMD1 or recombinant adeno-associated virus vector carrying TMD1 could be a promising antiangiogenesis strategy.

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Hydrostatic pressure promotes endothelial tube formation through aquaporin 1 and Ras-ERK signaling

Communications Biology ◽

10.1038/s42003-020-0881-9 ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Daisuke Yoshino ◽

Kenichi Funamoto ◽

Kakeru Sato ◽

Kenry ◽

Masaaki Sato ◽

...

Keyword(s):

Hydrostatic Pressure ◽

Tube Formation ◽

Erk Signaling ◽

Aquaporin 1 ◽

Endothelial Tube Formation

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Cardioprotective Activity of Selected Polyphenols Based on Epithelial and Aortic Cell Lines. A Review

Molecules ◽

10.3390/molecules25225343 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5343

Author(s):

Michał Otręba ◽

Leon Kośmider ◽

Jerzy Stojko ◽

Anna Rzepecka-Stojko

Keyword(s):

Endothelial Cells ◽

Tube Formation ◽

Health Claims ◽

In Vivo Studies ◽

Positive Effects ◽

Endothelial Tube Formation ◽

Disease Therapy ◽

Species Production

Polyphenols have recently gained popularity among the general public as products and diets classified as healthy and containing naturally occurring phenols. Many polyphenolic extracts are available on the market as dietary supplements, functional foods, or cosmetics, taking advantage of clients’ desire to live a healthier and longer life. However, due to the difficulty of discovering the in vivo functions of polyphenols, most of the research focuses on in vitro studies. In this review, we focused on the cardioprotective activity of different polyphenols as possible candidates for use in cardiovascular disease therapy and for improving the quality of life of patients. Thus, the studies, which were mainly based on endothelial cells, aortic cells, and some in vivo studies, were analyzed. Based on the reviewed articles, polyphenols have a few points of action, including inhibition of acetylcholinesterase, decrease in reactive oxygen species production and endothelial tube formation, stimulation of acetylcholine-induced endothelium-derived mediator release, and others, which lead to their cardio- and/or vasoprotective effects on endothelial cells. The obtained results suggest positive effects of polyphenols, but more long-term in vivo studies demonstrating effects on mechanism of action, sensitivity, and specificity or efficacy are needed before legal health claims can be made.

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10206 The effect of impulsive pressure on endothelial tube formation

The Proceedings of Conference of Kanto Branch ◽

10.1299/jsmekanto.2014.20._10206-1_ ◽

2014 ◽

Vol 2014.20 (0) ◽

pp. _10206-1_-_10206-2_

Author(s):

Eriko OTSU ◽

Hiromichi NAKADATE ◽

Shigeru AOMURA ◽

Akira KAKUTA

Keyword(s):

Tube Formation ◽

Endothelial Tube Formation ◽

Impulsive Pressure

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Atherogenic Cytokines Regulate VEGF-A-Induced Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Endothelial Cells

Stem Cells International ◽

10.1155/2015/498328 ◽

2015 ◽

Vol 2015 ◽

pp. 1-13 ◽

Cited By ~ 10

Author(s):

Izuagie Attairu Ikhapoh ◽

Christopher J. Pelham ◽

Devendra K. Agrawal

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Endothelial Cells ◽

Mesenchymal Stem Cells ◽

Tube Formation ◽

Ang Ii ◽

Induced Differentiation ◽

Endothelial Tube Formation ◽

Marker Expression

Coronary artery stenting or angioplasty procedures frequently result in long-term endothelial dysfunction or loss and complications including arterial thrombosis and myocardial infarction. Stem cell-based therapies have been proposed to support endothelial regeneration. Mesenchymal stem cells (MSCs) differentiate into endothelial cells (ECs) in the presence of VEGF-Ain vitro. Application of VEGF-A and MSC-derived ECs at the interventional site is a complex clinical challenge. In this study, we examined the effect of atherogenic cytokines (IL-6, TNFα, and Ang II) on EC differentiation and function. MSCs (CD44+, CD73+, CD90+, CD14−, and CD45−) were isolated from the bone marrow of Yucatan microswine. Naïve MSCs cultured in differentiation media containing VEGF-A (50 ng/mL) demonstrated increased expression of EC-specific markers (vWF, PECAM-1, and VE-cadherin), VEGFR-2 and Sox18, and enhanced endothelial tube formation. IL-6 or TNFαcaused a dose-dependent attenuation of EC marker expression in VEGF-A-stimulated MSCs. In contrast, Ang II enhanced EC marker expression in VEGF-A-stimulated MSCs. Addition of Ang II to VEGF-A and IL-6 or TNFαwas sufficient to rescue the EC phenotype. Thus, Ang II promotes but IL-6 and TNFαinhibit VEGF-A-induced differentiation of MSCs into ECs. These findings have important clinical implications for therapies intended to increase cardiac vascularity and reendothelialize coronary arteries following intervention.

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Stromal cell–derived factor 1 promotes angiogenesis via a heme oxygenase 1–dependent mechanism

Journal of Experimental Medicine ◽

10.1084/jem.20061609 ◽

2007 ◽

Vol 204 (3) ◽

pp. 605-618 ◽

Cited By ~ 170

Author(s):

Jessy Deshane ◽

Sifeng Chen ◽

Sergio Caballero ◽

Anna Grochot-Przeczek ◽

Halina Was ◽

...

Keyword(s):

Wound Healing ◽

Heme Oxygenase ◽

Stromal Cell ◽

Tube Formation ◽

Heme Oxygenase 1 ◽

Impaired Wound Healing ◽

Endothelial Tube Formation ◽

Stromal Cell Derived Factor ◽

And Migration

Stromal cell–derived factor 1 (SDF-1) plays a major role in the migration, recruitment, and retention of endothelial progenitor cells to sites of ischemic injury and contributes to neovascularization. We provide direct evidence demonstrating an important role for heme oxygenase 1 (HO-1) in mediating the proangiogenic effects of SDF-1. Nanomolar concentrations of SDF-1 induced HO-1 in endothelial cells through a protein kinase C ζ–dependent and vascular endothelial growth factor–independent mechanism. SDF-1–induced endothelial tube formation and migration was impaired in HO-1–deficient cells. Aortic rings from HO-1−/− mice were unable to form capillary sprouts in response to SDF-1, a defect reversed by CO, a byproduct of the HO-1 reaction. Phosphorylation of vasodilator-stimulated phosphoprotein was impaired in HO-1−/− cells, an event that was restored by CO. The functional significance of HO-1 in the proangiogenic effects of SDF-1 was confirmed in Matrigel plug, wound healing, and retinal ischemia models in vivo. The absence of HO-1 was associated with impaired wound healing. Intravitreal adoptive transfer of HO-1–deficient endothelial precursors showed defective homing and reendothelialization of the retinal vasculature compared with HO-1 wild-type cells following ischemia. These findings demonstrate a mechanistic role for HO-1 in SDF-1–mediated angiogenesis and provide new avenues for therapeutic approaches in vascular repair.

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Regulation and function of homeodomain proteins in the embryonic and adult vascular systemsThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigators' Forum.

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y06-091 ◽

2007 ◽

Vol 85 (1) ◽

pp. 55-65 ◽

Cited By ~ 15

Author(s):

Josette M. Douville ◽

Jeffrey T. Wigle

Keyword(s):

Transcription Factors ◽

Target Genes ◽

Vascular System ◽

Homeobox Genes ◽

Tube Formation ◽

Binding Motif ◽

Homeodomain Proteins ◽

Downstream Target ◽

Endothelial Tube Formation ◽

And Function

During embryonic development, the cardiovascular system first forms and then gives rise to the lymphatic vascular system. Homeobox genes are essential for both the development of the blood and lymphatic vascular systems, as well as for their maintenance in the adult. These genes all encode proteins that are transcription factors that contain a well conserved DNA binding motif, the homeodomain. It is through the homeodomain that these transcription factors bind to the promoters of target genes and regulate their expression. Although many homeodomain proteins have been found to be expressed within the vascular systems, little is known about their downstream target genes. This review highlights recent advances made in the identification of novel genes downstream of the homeodomain proteins that are necessary for regulating vascular cellular processes such as proliferation, migration, and endothelial tube formation. Factors known to regulate the functions of vascular cells via modulating the expression of homeobox genes will be discussed. We will also review current methods used to identify and characterize downstream target genes of homeodomain proteins.

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