scholarly journals Inhibition of Corneal Neovascularization by Subconjunctival Injection of Fc-Endostatin, a Novel Inhibitor of Angiogenesis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Junko Yoshida ◽  
Robert T. Wicks ◽  
Andrea I. Zambrano ◽  
Betty M. Tyler ◽  
Kashi Javaherian ◽  
...  
Keyword(s):  
Angiogenesis Inhibitor ◽  
Corneal Neovascularization ◽  
Subconjunctival Injection ◽  
Vascular Endothelial ◽  
Vessel Length ◽  
Treatment Groups ◽  
Significant Difference ◽  
Vessel Growth ◽  
Endothelial Growth Factor ◽  
Clinical Potential

We assessed the antiangiogenic effects of subconjunctival injection of Fc-endostatin (FcE) using a human vascular endothelial growth factor-induced rabbit corneal neovascularization model. Angiogenesis was induced in rabbit corneas through intrastromal implantations of VEGF polymer implanted 2 mm from the limbus. NZW rabbits were separated into groups receiving twice weekly subconjunctival injections of either saline; 25 mg/mL bevacizumab; 2 mg/mL FcE; or 20 mg/mL FcE. Corneas were digitally imaged at 5 time points. An angiogenesis index (AI) was calculated (vessel length (mm) × vessel number score) for each observation. All treatment groups showed a significant decrease in the vessel length and AI compared to saline on all observation days (P<0.001). By day 15, FcE 2 inhibited angiogenesis significantly better than FcE 20 (P<0.01). There was no significant difference between FcE 2 and BV, although the values trended towards significantly increased inhibition by BV. BV was a significantly better inhibitor than FcE 20 by day 8 (P<0.01). FcE was safe and significantly inhibited new vessel growth in a rabbit corneal neovascularization model. Lower concentration FcE 2 exhibited better inhibition than FcE 20, consistent with previous FcE studies referencing a biphasic dose-response curve. Additional studies are necessary to further elucidate the efficacy and clinical potential of this novel angiogenesis inhibitor.

scholarly journals The Effect of Miana (Coleus Scutellariodes [L]) on Vascular Endothelial Growth Factor Expression in Balb/C Mice Infected with Mycobacterium Tuberculosis

2021 ◽  
Vol 14 (2) ◽  
pp. 525-532
Author(s):  
Rosa Marlina ◽  
Mochammad Hatta ◽  
Eva Sridiana ◽  
Irawaty Djaharuddin ◽  
Ilhamjaya Patellongi ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Treatment Groups ◽  
Protein Levels ◽  
Significant Difference ◽  
Infection Focus ◽  
Ifn Γ ◽  
Endothelial Growth Factor ◽  
Vegf Level

Tuberculosis (TB) is still a major global health problem. The increasing prevalence of antibiotic resistance has posed a major threat towards the mission of TB eradication. Traditional medication has been a staple alternative and adjuvant to conventional treatment for Indonesians. Miana leaves (Coleus scutellariodes) is one such traditional medicine that has a potential role as immunoregulator, antiinflammation, and antimicrobial agent. Several studies have shown that Miana leaves extract can regulate TLR 4, the number of CD4 T cells, IFN-γ levels, and TNF-α.Vascular Endothelial Growth Factor (VEGF) mediates angiogenesis and vasodilatation to provide oxygenation and access for immune cells in hypoxic and inflamed site sue to infection focus. This study aims to study the effect of Miana leaves on VEGF expression. Balb/c mice were infected with Mycobacterium tuberculosis and were treated using Miana leaves extract, rifampicin, and rifampicin plus Miana. VEGF protein levels before infection, after infection, and after treatment were measured using ELISA. The results showed that there was a significant difference in VEGF level means between treatment groups. VEGF levels in rifampicin, Miana, and rifampicin plus Miana groups were significantly lower than placebo. VEGF level was significantly lower in rifampicin group compared to Miana group. VEGF level was significantly lower in rifampicin plus Miana group compared to Miana group. There was no significant difference of VEGF level between rifampicin and rifampicin plus Miana group. The results indicate that Maina leaves does have an effect on VEGF level in mice infection with Mycobacterium tuberculosis.

scholarly journals The VAD Scheme versus Thalidomide plus VAD for Reduction of Vascular Endothelial Growth Factor in Multiple Myeloma: A Meta-Analysis

2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Gan-Lin He ◽  
Duo-Rong Xu ◽  
Wai-Yi Zou ◽  
Sui-Zhi He ◽  
Juan Li
Keyword(s):  
Multiple Myeloma ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Meta Analysis ◽  
Biomedical Literature ◽  
Cochrane Library ◽  
Vascular Endothelial ◽  
China National Knowledge Infrastructure ◽  
Significant Difference ◽  
Endothelial Growth Factor

The VAD (vincristine-doxorubicin-dexamethasone) regimen has been used for decades to treat multiple myeloma (MM). Based on reports that vascular endothelial growth factor- (VEGF-) mediated angiogenesis is critical for MM pathogenesis, the antiangiogenic compound thalidomide has been added to VAD (T-VAD). However, it remains unclear whether T-VAD is more efficacious than VAD for serum VEGF reduction or if the difference influences clinical outcome. Pubmed, Cochrane library, China Biomedical Literature (CBM) database, China National Knowledge Infrastructure (CNKI) database, Vip database, and Wanfang database were searched for relevant studies published up to June 2017. RevMan5.2 was used for methodological quality evaluation and data extraction. Thirteen trials (five randomized, seven nonrandomized, and one historically controlled) involving 815 cases were included. Serum VEGF was significantly higher in MM cases than non-MM controls (MD=353.01, [95%CI 187.52–518.51], P<0.01), and the overall efficacy of T-VAD was higher than that of VAD (RR=1.36, [1.21–1.53], P <0.01). Further, T-VAD reduced VEGF to a greater extent than VAD does ([MD=-49.85, [-66.28− -33.42], P<0.01). The T-VAD regimen also reduced VEGF to a greater extent in newly diagnosed MM patients than it did in recurrent patients ([MD=-120.20, [-164.60–-39.80], P<0.01). There was no significant difference in VEGF between T-VAD patients (2 courses) and nontumor controls (MD=175.94, [-26.08–377.95], P=0.09). Greater serum VEGF reduction may be responsible for the superior efficacy of T-VAD compared to VAD.

scholarly journals De-novo multilayering in fibrovascular pigment epithelial detachment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Manoj Soman ◽  
Jay U. Sheth ◽  
Asmita Indurkar ◽  
Padmanabhan Meleth ◽  
Unnikrishnan Nair
Keyword(s):  
De Novo ◽  
Median Number ◽  
Final Visit ◽  
Low Grade ◽  
Vascular Endothelial ◽  
Pigment Epithelial Detachment ◽  
Pigment Epithelial ◽  
Anti Vegf ◽  
Significant Difference ◽  
Endothelial Growth Factor

AbstractThis study describes the occurrence of multilayered pigment-epithelial detachment (MLPED) as a De-novo phenomenon (DN-MLPED) and compare the features with multi-layering secondary to chronic anti-vascular endothelial growth factor (anti-VEGF) therapy (s-MLPED). We did a retrospective evaluation of spectral-domain optical coherence tomography (SD-OCT) features, treatment-profile, and visual-acuity (VA) outcomes in eyes with MLPED. Out of 17 eyes with MLPED, 7 eyes had DN-MLPED and 10 eyes had s-MLPED. There was no significant difference in baseline and final VA between the groups. At the final visit, no significant visual improvement was noted in both the groups, although a possible trend towards an improvement was seen in DN-MLPED eyes while the s-MLPED demonstrated a declining trend (DN-MLPED—LogMAR-BCVA: Baseline = 0.79 [∼ 20/123] ± 0.91; Final = 0.76 [∼ 20/115] ± 0.73; p = 0.87; s-MLPED—LogMAR BCVA: Baseline = 0.43 [∼ 20/54] ± 0.68; Final = 0.94 [∼ 20/174] ± 0.71; p = 0.06). Moreover, after presentation, the median number of injections in DN-MLPED eyes were significantly lower compared to s-MLPED eyes (DN-MLPED:4; s-MLPED:12; p = 0.03) (Median follow-up: DN-MLPED = 26 months; s-MLPED = 54 months; p = 0.15). Subretinal hyperreflective-material (SHRM) deposition heralded the onset of multilayering and was seen to progress in all DN-PED eyes and 1/4 eyes of s-MLPED. To conclude, MLPED is a unique form of cicatrizing fibrovascular-PED which can evolve denovo too. Long-standing disease with intermittent or low-grade activity can potentially explain this unique phenomenon. With fewer anti-VEGF therapy, the de-novo MLPED eyes show more visual stability as compared to s-MLPED eyes.

scholarly journals Vascular Endothelial Growth Factor Concentration in Brain of Rat Treated with Anaerobic Exercises

2015 ◽  
Vol 4 (3) ◽  
pp. 201
Author(s):  
Rostika Flora ◽  
Muhammad Zulkarnain ◽  
Yuliana Ardi ◽  
Esti Sorena ◽  
Roslina Wati ◽  
...  
Keyword(s):  
Wistar Rat ◽  
Anaerobic Exercise ◽  
Control Group ◽  
Vascular Endothelial ◽  
Exercise Frequency ◽  
Treatment Groups ◽  
The One ◽  
Short Time ◽  
Endothelial Growth Factor ◽  
Brain Tissues

Anaerobic  exercise is a high-intensity exercise that needs quick energy supplies obtained in a very short time. However, this exercise may result in tissue hypoxia which is characterized by the increase of HIF-1α concentration. The presence of HIF-1α will induce the secretion of VEGF and, eventually, trigger angiogenesis. Nevertheless, it is still unclear whether anaerobic exercise will also cause hypoxia in which this condition will increase the concentration of VEGF in brain tissues. The aim of this study was to find out the effect of anaerobic exercise frequency towards VEGF concentration of Wistar rat brain tissues.  Brain tissues were taken from rats treated with anaerobic exercise using treadmill. This exercise was given in different frequencies; one time, three times, and seven times a week.  The data collected were analyzed using independent t-test. The results of this study showed that anaerobic  exercise done once a week could significantly increase VEGF concentration (p &lt; 0.05) if compared with the one in control group (95.21 ± 31.99 v.s. 63.36 ± 11.01 pg/mL). Meanwhile, VEGF concentration of treatment groups given exercise three times a week (47.97 ± 10.68 pg/mL) and seven times a week (40.56 ± 13.98 pg/mL) showed a significant decrease if compared with that of control group (63.36 ± 11.01 pg/mL). Anaerobic  exercise affected VEGF concentration as an indicator of angiogenesis in brain tissue of wistar rats.

Taming of the wild vessel: promoting vessel stabilization for safe therapeutic angiogenesis

2011 ◽  
Vol 39 (6) ◽  
pp. 1654-1658 ◽  
Author(s):  
Silvia Reginato ◽  
Roberto Gianni-Barrera ◽  
Andrea Banfi
Keyword(s):  
Current Knowledge ◽  
Single Gene ◽  
Therapeutic Angiogenesis ◽  
Maturation Stage ◽  
Vascular Endothelial ◽  
Cellular Regulation ◽  
Vessel Growth ◽  
Vascular Structures ◽  
Endothelial Growth Factor ◽  
Vascular Maturation

VEGF (vascular endothelial growth factor) is the master regulator of blood vessel growth. However, it displayed substantial limitations when delivered as a single gene to restore blood flow in ischaemic conditions. Indeed, uncontrolled VEGF expression can easily induce aberrant vascular structures, and short-term expression leads to unstable vessels. Targeting the second stage of the angiogenic process, i.e. vascular maturation, is an attractive strategy to induce stable and functional vessels for therapeutic angiogenesis. The present review discusses the limitations of VEGF-based gene therapy, briefly summarizes the current knowledge of the molecular and cellular regulation of vascular maturation, and describes recent pre-clinical evidence on how the maturation stage could be targeted to achieve therapeutic angiogenesis.

Systemic conbercept pharmacokinetics and VEGF pharmacodynamics following intravitreal injections of conbercept in patients with retinopathy of prematurity

2021 ◽  
pp. bjophthalmol-2021-319131
Author(s):  
Yong Cheng ◽  
Shuang Sun ◽  
Xun Deng ◽  
Xuemei Zhu ◽  
Dandan Linghu ◽  
...  
Keyword(s):  
Retinopathy Of Prematurity ◽  
Intravitreal Injections ◽  
Vascular Endothelial ◽  
Randomised Study ◽  
Limit Of Quantitation ◽  
Significant Difference ◽  
Endothelial Growth Factor ◽  
Type 1 Rop

BackgroundData on serum vascular endothelial growth factor (VEGF) and drug levels in patients with retinopathy of prematurity (ROP) following intravitreal injections of conbercept (IVC) are lacking.MethodsMulticentre, prospective, non-randomised study of patients with aggressive posterior retinopathy of prematurity (APROP) or type 1 ROP who had not received other treatment. All infants received therapy in both eyes plus intravitreal IVC 0.25 mg/0.025 mL in one eye and had at least 6 months of follow-up. Blood samples were collected before and 1 week and 4 weeks after IVC. The main outcome measures were serum conbercept and VEGF concentrations.ResultsForty infants with APROP or type 1 ROP were enrolled. The mean serum VEGF at baseline and 1 week and 4 weeks after a total of 0.25 mg of IVC was 953.35±311.90 pg/mL, 303.46±181.89 pg/mL and 883.12±303.89 pg/mL, respectively. Serum VEGF 1 week after IVC was significantly lower (p<0.05) than baseline, and at 4 weeks after IVC, it was significantly higher (p<0.05) than at 1 week. There was no significant difference (p>0.05) between baseline and 4 weeks. Serum conbercept was below the limit of quantitation (BLOQ) at baseline and 4 weeks and was 19.81±7.60 ng/mL at 1 week.ConclusionSerum VEGF 1 week after IVC was significantly lower than baseline but returned to baseline at 4 weeks. Serum conbercept increased at 1 week and was BLOQ at 4 weeks.

scholarly journals MMP-9 gene deletion mitigates microvascular loss in a model of ischemic acute kidney injury

2011 ◽  
Vol 301 (1) ◽  
pp. F101-F109 ◽  
Author(s):  
So-Young Lee ◽  
Markus Hörbelt ◽  
Henry E. Mang ◽  
Nicole L. Knipe ◽  
Robert L. Bacallao ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Gene Deletion ◽  
Kidney Injury ◽  
Ischemic Injury ◽  
Microvascular Density ◽  
Vascular Endothelial ◽  
Significant Difference ◽  
Bilateral Renal Artery ◽  
Endothelial Growth Factor ◽  
Microvascular Rarefaction

Microvascular rarefaction following an episode of acute kidney injury (AKI) is associated with renal hypoxia and progression toward chronic kidney disease. The mechanisms contributing to microvascular rarefaction are not well-understood, although disruption in local angioregulatory substances is thought to contribute. Matrix metalloproteinase (MMP)-9 is an endopeptidase important in modifying the extracellular matrix (ECM) and remodeling the vasculature. We examined the role of MMP-9 gene deletion on microvascular rarefaction in a rodent model of ischemic AKI. MMP-9-null mice and background control (FVB/NJ) mice were subjected to bilateral renal artery clamping for 20 min followed by reperfusion for 14, 28, or 56 days. Serum creatinine level in MMP-9-null mice 24 h after injury [1.4 (SD 0.8) mg/dl] was not significantly different from FVB/NJ mice [1.5 (SD 0.6) mg/dl]. Four weeks after ischemic injury, FVB/NJ mice demonstrated a 30–40% loss of microvascular density compared with sham-operated (SO) mice. In contrast, microvascular density was not significantly different in the MMP-9-null mice at this time following injury compared with SO mice. FVB/NJ mice had a 50% decrease in tissue vascular endothelial growth factor (VEGF) 2 wk after ischemic insult compared with SO mice. A significant difference in VEGF was not observed in MMP-9-null mice compared with SO mice. There was no significant difference in the liberation of angioinhibitory fragments from the ECM between MMP-9-null mice and FVB/NJ mice following ischemic injury. In conclusion, MMP-9 deletion stabilizes microvascular density following ischemic AKI in part by preserving tissue VEGF levels.

Measurement of free and complexed soluble vascular endothelial growth factor receptor, Flt-1, in fluid samples: development and application of two new immunoassays

2001 ◽  
Vol 100 (5) ◽  
pp. 567-575 ◽  
Author(s):  
Funmi M. BELGORE ◽  
Andrew D. BLANN ◽  
Gregory Y. LIP
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cell ◽  
Growth Factor ◽  
Plasma Levels ◽  
Biological Significance ◽  
Growth Factor Receptor ◽  
Soluble Form ◽  
Vascular Endothelial ◽  
Significant Difference ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) mediates endothelial cell mitogenesis and enhances vascular permeability. VEGF interacts with the endothelium via two membrane-spanning receptors, fms-like tyrosine kinase (Flt)-1 and kinase domain receptor. A soluble form of Flt-1 (sFlt-1) was isolated from endothelial cell media; however, its biological significance is still unknown, with limited data on plasma sFlt-1 levels in disease states. We have developed two new ELISAs for detecting free and VEGF-complexed sFlt-1, which were tested in accordance with standard validation and assessment methodologies employed in commercial settings. The intra-and inter-assay coefficients of variation are < 5% and 10% respectively, and results are highly reproducible. Applying these ELISAs in a clinical setting, we measured levels of VEGF, free and complexed sFlt-1 in citrated plasma from 40 patients with cardiovascular disease and 40 healthy controls. Median (interquartile range) plasma levels of VEGF in patients were significantly greater than controls [403 pg/ml (158–925 pg/ml) versus 113 pg/ml (33–231 pg/ml), P ⩽ 0.05]. Free sFlt-1 was significantly lower in patients compared with controls [8 ng/ml (2–22 ng/ml) versus 21 ng/ml (10–73 ng/ml), P ⩽ 0.05]. There was no significant difference in the levels of complexed sFlt-1 between the two groups. Plasma levels of VEGF-complexed sFlt-1 are minimal, despite the presence of excess free sFlt-1. Thus unbound plasma VEGF detected by ELISA may represent the majority of circulating VEGF, and justifies the measurement of plasma VEGF as an indicator of circulating VEGF levels. Furthermore, these results suggest that circulating sFlt-1 may serve as a selective inhibitor of VEGF activity, and that this regulatory mechanism may be altered by pathological conditions.

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