scholarly journals Bis(maltolato)oxovanadium(IV) Induces Angiogenesis via Phosphorylation of VEGFR2

2020 ◽  
Vol 21 (13) ◽  
pp. 4643
Author(s):  
Laura Parma ◽  
Hendrika A.B. Peters ◽  
Maria E. Johansson ◽  
Saray Gutiérrez ◽  
Henk Meijerink ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Ex Vivo ◽  
Protein Tyrosine Phosphatases ◽  
Aortic Ring ◽  
Tube Formation ◽  
Aortic Ring Assay ◽  
In Vitro Angiogenesis

VEGFR2 and VEGF-A play a pivotal role in the process of angiogenesis. VEGFR2 activation is regulated by protein tyrosine phosphatases (PTPs), enzymes that dephosphorylate the receptor and reduce angiogenesis. We aim to study the effect of PTPs blockade using bis(maltolato)oxovanadium(IV) (BMOV) on in vivo wound healing and in vitro angiogenesis. BMOV significantly improves in vivo wound closure by 45% in C57BL/6JRj mice. We found that upon VEGFR2 phosphorylation induced by endogenously produced VEGF-A, the addition of BMOV results in increased cell migration (45%), proliferation (40%) and tube formation (27%) in HUVECs compared to control. In a mouse ex vivo, aortic ring assay BMOV increased the number of sprouts by 3 folds when compared to control. However, BMOV coadministered with exogenous VEGF-A increased ECs migration, proliferation and tube formation by only 41%, 18% and 12% respectively and aortic ring sprouting by only 1-fold. We also found that BMOV enhances VEGFR2 Y951 and p38MAPK phosphorylation, but not ERK1/2. The level of phosphorylation of these residues was the same in the groups treated with BMOV supplemented with exogenous VEGF-A and exogenous VEGF-A only. Our study demonstrates that BMOV is able to enhance wound closure in vivo. Moreover, in the presence of endogenous VEGF-A, BMOV is able to stimulate in vitro angiogenesis by increasing the phosphorylation of VEGFR2 and its downstream proangiogenic enzymes. Importantly, BMOV had a stronger proangiogenic effect compared to its effect in coadministration with exogenous VEGF-A.

7E3 F(ab’)2, an Effective Antagonist of Rat αIIbβ3 and αvβ3, Blocks In Vivo Thrombus Formation and In Vitro Angiogenesis

2001 ◽  
Vol 85 (05) ◽  
pp. 896-902 ◽  
Author(s):  
Patricia Sassoli ◽  
Eva Emmell ◽  
Susan Tam ◽  
Mohit Trikha ◽  
Zhao Zhou ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Ex Vivo ◽  
Thrombus Formation ◽  
Aortic Ring ◽  
Canine Models ◽  
Sprout Formation ◽  
Double Crush ◽  
In Vitro Angiogenesis

SummaryAbciximab (c7E3 Fab, ReoPro®) blocks GPIIb/IIIa and αvβ3 and inhibits thrombotic and proliferative events only in humans and non-human primates. The bivalent F(ab’)2 fragment is an effective anti-thrombotic agent in canine models. In the present study, 7E3 F(ab’)2 was also found to bind to rat GPIIb/IIIa (KD = 27 ± 4 g/mL) and αvβ3 (KD = 9 ± 8 μg/mL), to block in vitro rat platelet aggregation (IC50 = 16 ± 6 μg/mL), and to inhibit αvβ3-mediated microvessel sprout formation in a rat aortic ring assay. Following administration of 7E3 F(ab’)2 (4 mg/kg) to rats, platelet aggregation was completely blocked for up to 6 h and thrombus formation in response to a rat abdominal aorta double crush injury was prevented. Effective chronic dosing was achieved with 6 mg/kg daily I.P. injections. In vitro mixing experiments indicated that 7E3 F(ab’)2 redistributed to unlabeled platelets in 2 h. Ex vivo, 7E3 F(ab’)2 was detected on platelets for up to 4 days after a single 4-mg/kg injection. These data suggest that 7E3 F(ab’)2 may be a useful agent to study the effects of GPIIb/IIIa and αvβ3 blockade in rat models of thrombosis and vascular disease.

Esculetin Inhibits VEGF-Induced Angiogenesis Both In Vitro and In Vivo

2016 ◽  
Vol 44 (01) ◽  
pp. 61-76 ◽  
Author(s):  
Sung Lyea Park ◽  
Se Yeon Won ◽  
Jun-Hui Song ◽  
Sook-Young Lee ◽  
Wun-Jae Kim ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Aortic Ring ◽  
Tube Formation ◽  
Phase Cell ◽  
Ex Vivo Model ◽  
Downstream Signaling ◽  
And Migration ◽  
Effective Use

Esculetin is known to inhibit tumor growth, but its effect in angiogenesis has not been studied. Here, we report the efficacy of esculetin on VEGF-induced angiogenesis. Esculetin treatment inhibited VEGF-induced proliferation and DNA synthesis of HUVECs with no cell toxicity. G1-phase cell-cycle arrest was associated with a decreased expression of cyclins and CDKs via the binding of p27KIP1. Esculetin down-regulated the MMP-2 expression in VEGF-stimulated HUVECs, which suppressed colony tube formation and migration. Esculetin reduced the phosphorylation of VEGFR-2 and the downstream signaling of VEGFR-2, including ERK1/2 and eNOS/Akt pathways. Esculetin suppressed microvessel outgrowth from an aortic ring ex vivo model treated with VEGF, and blocked the VEGF-induced formation of new blood vessels and hemoglobin content in an in vivo Matrigel plug model. Collectively, VEGF-stimulated responses in angiogenesis were inhibited in vitro and in vivo, providing a theoretical basis for effective use against anti-angiogenic therapies.

Ethanol Extract of Achillea fragrantissima Enhances Angiogenesis through Stimulation of VEGF Production

2020 ◽  
Vol 21 ◽  
Author(s):  
Hana M. Hammad ◽  
Amer Imraish ◽  
Maysa Al-Hussaini ◽  
Malek Zihlif ◽  
Amani A. Harb ◽  
...  
Keyword(s):  
Wound Healing ◽  
Rural Communities ◽  
Ex Vivo ◽  
Ethanol Extract ◽  
Aortic Ring ◽  
Treated Group ◽  
Control Group ◽  
Dependent Manner ◽  
Achillea Fragrantissima

Objective: Achillea fragrantissima L. (Asteraceae) is a traditionally used medicinal herb in the rural communities of Jordan. Methods: The present study evaluated the efficacy of the ethanol extract of this species on angiogenesis in both, ex vivo using rat aortic ring assay and in vivo using rat excision wound model. Results: In concentrations of 50 and 100 µg/ml, the ethanol extract showed angiogenic stimulatory effect and significantly increased length of capillary protrusions around aorta rings of about 60% in comparison to those of untreated aorta rings. In MCF-7 cells, the ethanol extract of A. fragrantissima stimulates the production of VEGF in a dose-dependent manner. 1% and 5% of ethanol extract of A. fragrantissima containing vaseline based ointment was applied on rat excision wounds for six days and was found to be effective in wound healing and maturation of the scar. Both preparations resulted in better wound healing when compared to the untreated control group and vaseline-treated group. This effect was comparable to that induced by MEBO, the positive control. Conclusion: The results indicate that A. fragrantissima has a pro-angiogenic effect, which may act through the VEGF signaling pathway.

scholarly journals Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure

2019 ◽  
Vol 20 (15) ◽  
pp. 3679 ◽  
Author(s):  
Lin Chen ◽  
Alyne Simões ◽  
Zujian Chen ◽  
Yan Zhao ◽  
Xinming Wu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Oral Mucosa ◽  
Wound Closure ◽  
Expression Patterns ◽  
Skin Wound ◽  
Skin Wound Healing ◽  
Specific Expression ◽  
Keratinocyte Proliferation

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

scholarly journals Preclinical Evaluation of Discorhabdins in Antiangiogenic and Antitumor Models

Marine Drugs ◽  
2018 ◽  
Vol 16 (7) ◽  
pp. 241 ◽  
Author(s):  
Emily Harris ◽  
Jonathan Strope ◽  
Shaunna Beedie ◽  
Phoebe Huang ◽  
Andrew Goey ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Hypoxia Inducible Factor ◽  
Xenograft Model ◽  
Aortic Ring ◽  
Therapeutic Benefit ◽  
Tube Formation ◽  
Endothelial Cell Proliferation ◽  
System A ◽  
Oncogenic Transcription Factor

Elements of the hypoxia inducible factor (HIF) transcriptional system, a key regulator of the cellular hypoxic response, are up-regulated in a range of cancer cells. HIF is fundamentally involved in tumor angiogenesis, invasion, and energy metabolism. Inhibition of the transcriptional activity of HIF may be of therapeutic benefit to cancer patients. We recently described the identification of two marine pyrroloiminoquinone alkaloids with potent activity in inhibiting the interaction between the oncogenic transcription factor HIF-1α and the coactivator protein p300. Herein, we present further characterization data for these two screening hits: discorhabdin H (1) and discorhabdin L (2), with a specific focus on their anti-angiogenic and anti-tumor effects. We demonstrated that only discorhabdin L (2) possesses excellent anti-angiogenic activity in inhibiting endothelial cell proliferation and tube formation, as well as decreasing microvessel outgrowth in the ex vivo rat aortic ring assay. We further showed that discorhabdin L (2) significantly inhibits in vivo prostate tumor growth in a LNCaP xenograft model. In conclusion, our findings suggest that discorhabdin L (2) represents a promising HIF-1α inhibitor worthy of further drug development.

scholarly journals Continuous Delivery of Stromal Cell-Derived Factor-1 from Alginate Scaffolds Accelerates Wound Healing

2010 ◽  
Vol 19 (4) ◽  
pp. 399-408 ◽  
Author(s):  
Sina Y. Rabbany ◽  
Joseph Pastore ◽  
Masaya Yamamoto ◽  
Tim Miller ◽  
Shahin Rafii ◽  
...  
Keyword(s):  
Wound Healing ◽  
Stromal Cell ◽  
Wound Closure ◽  
Tissue Injury ◽  
Unmet Need ◽  
Novel Therapy ◽  
Yorkshire Pigs ◽  
Stromal Cell Derived Factor

Proper wound diagnosis and management is an increasingly important clinical challenge and is a large and growing unmet need. Pressure ulcers, hard-to-heal wounds, and problematic surgical incisions are emerging at increasing frequencies. At present, the wound-healing industry is experiencing a paradigm shift towards innovative treatments that exploit nanotechnology, biomaterials, and biologics. Our study utilized an alginate hydrogel patch to deliver stromal cell-derived factor-1 (SDF-1), a naturally occurring chemokine that is rapidly overexpressed in response to tissue injury, to assess the potential effects SDF-1 therapy on wound closure rates and scar formation. Alginate patches were loaded with either purified recombinant human SDF-1 protein or plasmid expressing SDF-1 and the kinetics of SDF-1 release were measured both in vitro and in vivo in mice. Our studies demonstrate that although SDF-1 plasmid- and protein-loaded patches were able to release therapeutic product over hours to days, SDF-1 protein was released faster (in vivo Kd 0.55 days) than SDF-1 plasmid (in vivo Kd 3.67 days). We hypothesized that chronic SDF-1 delivery would be more effective in accelerating the rate of dermal wound closure in Yorkshire pigs with acute surgical wounds, a model that closely mimics human wound healing. Wounds treated with SDF-1 protein ( n = 10) and plasmid ( n = 6) loaded patches healed faster than sham ( n = 4) or control ( n = 4). At day 9, SDF-1-treated wounds significantly accelerated wound closure (55.0 ± 14.3% healed) compared to nontreated controls (8.2 ± 6.0%, p < 0.05). Furthermore, 38% of SDF-1-treated wounds were fully healed at day 9 (vs. none in controls) with very little evidence of scarring. These data suggest that patch-mediated SDF-1 delivery may ultimately provide a novel therapy for accelerating healing and reducing scarring in clinical wounds.

Development of Curcumin loaded chitosan polymer based nanoemulsion gel: In vitro, ex vivo evaluation and in vivo wound healing studies

2017 ◽  
Vol 101 ◽  
pp. 569-579 ◽  
Author(s):  
Lydia Thomas ◽  
Foziyah Zakir ◽  
Mohd. Aamir Mirza ◽  
Md. Khalid Anwer ◽  
Farhan Jalees Ahmad ◽  
...  
Keyword(s):  
Wound Healing ◽  
Ex Vivo ◽  
Nanoemulsion Gel

scholarly journals Development and Evaluation of Alginate Membranes with Curcumin-Loaded Nanoparticles for Potential Wound-Healing Applications

Pharmaceutics ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 389 ◽  
Author(s):  
Mónica C. Guadarrama-Acevedo ◽  
Raisa A. Mendoza-Flores ◽  
María L. Del Prado-Audelo ◽  
Zaida Urbán-Morlán ◽  
David M. Giraldo-Gomez ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Dressing ◽  
Clinical Performance ◽  
Ex Vivo ◽  
High Capacity ◽  
Wound Dressings ◽  
In Vivo Studies ◽  
Potential Use

Non-biodegradable materials with a low swelling capacity and which are opaque and occlusive are the main problems associated with the clinical performance of some commercially available wound dressings. In this work, a novel biodegradable wound dressing was developed by means of alginate membrane and polycaprolactone nanoparticles loaded with curcumin for potential use in wound healing. Curcumin was employed as a model drug due to its important properties in wound healing, including antimicrobial, antifungal, and anti-inflammatory effects. To determine the potential use of wound dressing, in vitro, ex vivo, and in vivo studies were carried out. The novel membrane exhibited the diverse functional characteristics required to perform as a substitute for synthetic skin, such as a high capacity for swelling and adherence to the skin, evidence of pores to regulate the loss of transepidermal water, transparency for monitoring the wound, and drug-controlled release by the incorporation of nanoparticles. The incorporation of the nanocarriers aids the drug in permeating into different skin layers, solving the solubility problems of curcumin. The clinical application of this system would cover extensive areas of mixed first- and second-degree wounds, without the need for removal, thus decreasing the patient’s discomfort and the risk of altering the formation of the new epithelium.

scholarly journals Exosomes derived from induced vascular progenitor cells promote angiogenesis in vitro and in an in vivo rat hindlimb ischemia model

2019 ◽  
Vol 317 (4) ◽  
pp. H765-H776 ◽  
Author(s):  
Takerra K. Johnson ◽  
Lina Zhao ◽  
Dihan Zhu ◽  
Yang Wang ◽  
Yan Xiao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Progenitor Cells ◽  
Ex Vivo ◽  
Aortic Ring ◽  
Size Exclusion ◽  
Hindlimb Ischemia ◽  
Vascular Progenitor Cells ◽  
Angiogenic Effect

Induced vascular progenitor cells (iVPCs) were created as an ideal cell type for regenerative medicine and have been reported to positively promote collateral blood flow and improve cardiac function in a rat model of myocardial ischemia. Exosomes have emerged as a novel biomedicine that mimics the function of the donor cells. We investigated the angiogenic activity of exosomes from iPVCs (iVPC-Exo) as a cell-free therapeutic approach for ischemia. Exosomes from iVPCs and rat aortic endothelial cells (RAECs) were isolated using a combination of ultrafiltration and size-exclusion chromatography. Nanoparticle tracking analysis revealed that exosome isolates fell within the exosomal diameter (<150 nm). These exosomes contained known markers Alix and TSG101, and their morphology was validated using transmission electron microscopy. When compared with RAECs, iVPCs significantly increased the secretion of exosomes. Cardiac microvascular endothelial cells and aortic ring explants were pretreated with RAEC-Exo or iVPC-Exo, and basal medium was used as a control. iVPC-Exo exerted an in vitro angiogenic effect on the proliferation, tube formation, and migration of endothelial cells and stimulated microvessel sprouting in an ex vivo aortic ring assay. Additionally, iVPC-Exo increased blood perfusion in a hindlimb ischemia model. Proangiogenic proteins (pentraxin-3 and insulin-like growth factor-binding protein-3) and microRNAs (-143-3p, -291b, and -20b-5p) were found to be enriched in iVPC-Exo, which may mediate iVPC-Exo induced vascular growth. Our findings demonstrate that treatment with iVPC-Exo promotes angiogenesis in vitro, ex vivo, and in vivo. Collectively, these findings indicate a novel cell-free approach for therapeutic angiogenesis. NEW & NOTEWORTHY The results of this work demonstrate exosomes as a novel physiological mechanism by which induced vascular progenitor cells exert their angiogenic effect. Moreover, angiogenic cargo of proteins and microRNAs may define the biological contributors in activating endothelial cells to form a new capillary plexus for ischemic vascular diseases. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/angiogenic-exosomes-from-vascular-progenitor-cells/ .

scholarly journals JunB is required for endothelial cell morphogenesis by regulating core-binding factor β

2006 ◽  
Vol 175 (6) ◽  
pp. 981-991 ◽  
Author(s):  
Alexander H. Licht ◽  
Oliver T. Pein ◽  
Lore Florin ◽  
Bettina Hartenstein ◽  
Hendrik Reuter ◽  
...  
Keyword(s):  
Target Gene ◽  
Tube Formation ◽  
Cell Morphogenesis ◽  
Core Binding Factor ◽  
Binding Factor ◽  
Endothelial Functions ◽  
Runx Proteins ◽  
In Vitro Angiogenesis

The molecular mechanism triggering the organization of endothelial cells (ECs) in multicellular tubules is mechanistically still poorly understood. We demonstrate that cell-autonomous endothelial functions of the AP-1 subunit JunB are required for proper endothelial morphogenesis both in vivo in mouse embryos with endothelial-specific ablation of JunB and in in vitro angiogenesis models. By cDNA microarray analysis, we identified core-binding factor β (CBFβ), which together with the Runx proteins forms the heterodimeric core-binding transcription complex CBF, as a novel JunB target gene. In line with our findings, expression of the CBF target MMP-13 was impaired in JunB-deficient ECs. Reintroduction of CBFβ into JunB-deficient ECs rescued the tube formation defect and MMP-13 expression, indicating an important role for CBFβ in EC morphogenesis.

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