Adrenomedullin administration alters vascular endothelial growth factor levels in rats in cold stress

Abstract Background: Many endogenous peptides play important regulatory roles in angiogenesis by modulating endothelial cell behavior. Adrenomedullin (AdM) is one of such factors. Angiogenesis and vascular endothelial growth factor (VEGF) are indistinguishable. Exposure to cold environment stimulates capillary angiogenesis. Objectives: Examine the effect of the bioactive peptide AdM on VEGF levels in rat liver, lung, brain, and heart tissues after cold stress treatment. Methods: Male wistar rats were divided into four groups as control, AdM treatment, cold stress and AdM+cold stress treated groups. In AdM-treated group, animals received intraperitoneal injection of AdM (2000 ng/kg body weight) once a day during a week. For the cold stress exposure, the rats were kept in separate cages at 10°C for a week. Results: The administration of AdM increased VEGF levels in all tissues in cold exposed rats. Conclusion: AdM may be a major regulatory factor in angiogenesis by modulating VEGF levels that is closely associated with cold exposure-related metabolic stimulation.

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T-cell receptor (TCR) repertoire in metastatic renal cell carcinoma (RCC) patients treated with first-line vascular endothelial growth factor receptor blockade.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.501 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 501-501

Author(s):

Thai Huu Ho ◽

Robert Charles Gagnon ◽

Yuan Liu ◽

F. Stephen Hodi ◽

Sabina Signoretti ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

T Cell ◽

Growth Factor ◽

Growth Factor Receptor ◽

Progression Free Survival ◽

Treated Group ◽

Phase Iii ◽

Vascular Endothelial ◽

Cell Repertoire ◽

Endothelial Growth Factor

501 Background: Reports have demonstrated an inverse relationship between suppression of immune surveillance mechanisms and activation of the vascular endothelial growth factor receptor (VEGFR) pathway suggesting that T cell repertoires may impact response to VEGFR blockade. We evaluated the association between clinical outcomes and T cell repertoire in metastatic RCC patients receiving a front-line anti-VEGFR, pazopanib. Methods: Pre-treatment RCC tumors were analyzed from VEG105192, a phase III study of mRCC patients randomized (2:1) to pazopanib (paz) 800 mg daily vs placebo (pbo) for TCR gamma (TCRG) and TCR beta (TCRB) CDR3 regions. Using the Adaptive Biotechnologies immunoSEQ Assay, we assessed TCR clonality, a measure of total repertoire represented by expanded clones, and entropy, a measure of evenness and diversity. PD-L1 was evaluated by immunohistochemistry (IHC) H-Scores. The goal of the study was to determine if the repertoire of T cell clones was associated with progression-free survival as a clinical endpoint. Results: In the cohort with available tissue, the median PFS was 10.8 and 5.5 months (mos) for paz and pbo, respectively. TCRB (n = 114) and TCRG (n = 43 pbo, 109 paz) clonality ranged from 0-0.31 and 0-0.98, and entropy from 1-12.1 and 0-10.37, respectively. TCRB and TCRG entropy were highly correlated (Spearman’s R = 0.92, n = 114). Samples from the pbo-treated group with higher TCRG entropy, defined as the top 25th percentile, were associated with an improved median PFS (12.8 months) when compared to the lower 75th percentile (3.1 months, P = 0.023); similar trends were seen for TCRB entropy. Neither entropy nor clonality was associated with maximal reduction in tumor volume in the paz-treated group. PD-L1 H-scores were not associated with entropy or clonality (P > 0.05). Conclusions: Our data suggests that RCC samples with higher entropy are associated with a favorable prognosis. Identification of tumors with restricted TCRB/G chain usage and less diverse repertoire, as represented by lower entropy and higher clonality, may impact responses to VEGFR blockade and requires further study. Clinical trial information: NCT00334282.

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The Impact of Experimental Preconditioning Using Vascular Endothelial Growth Factor in Stroke and Subarachnoid Hemorrhage

Stroke Research and Treatment ◽

10.1155/2013/948783 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Sven Oliver Eicker ◽

Moritz Hoppe ◽

Nima Etminan ◽

Stephan Macht ◽

Jason Perrin ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Subarachnoid Hemorrhage ◽

Growth Factor ◽

Infarct Volume ◽

Vascular Diseases ◽

Treated Group ◽

Vascular Endothelial ◽

Endothelial Growth Factor ◽

The Impact ◽

Major Stroke

Vascular endothelial growth factor (VEGF) stimulating angiogenesis was shown to be a potential novel therapeutic approach for the treatment of ischemic vascular diseases. The goal of the present study was to examine whether transfection of VEGF before occurrence of major stroke (part I) and cerebral vasospasm after experimental subarachnoid hemorrhage (SAH; part II) develops neuroprotective qualities. A total of 25 (part I) and 26 (part II) brains were analyzed, respectively. In part one, a significant reduction of infarct volume in the VEGF-treated stroke animals (43% reduction,P<0.05) could be detected. In part two, significant vasospasm was induced in all hemorrhage groups(P<0.02). Analyzing microperfusion, a significant higher amount of perfused vessels could be detected(P<0.01), whereas no significant effect could be detected towards macroperfusion. Histologically, no infarctions were observed in the VEGF-treated SAH group and the sham-operated group. Minor infarction in terms of vasospasm-induced small lesions could be detected in the control vector transduced group(P=0.05)and saline-treated group(P=0.09). The present study demonstrates the preconditioning impact of systemic intramuscular VEGF injection in animals after major stroke and induced severe vasospasm after SAH.

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Stimulation of endothelial progenitor cells by microRNA-31a-5p to induce endothelialization in an aneurysm neck after coil embolization by modulating the Axin1-mediated β-catenin/vascular endothelial growth factor pathway

Journal of Neurosurgery ◽

10.3171/2019.5.jns182901 ◽

2020 ◽

Vol 133 (3) ◽

pp. 918-926 ◽

Cited By ~ 2

Author(s):

Guo Yu ◽

Peixi Liu ◽

Yuan Shi ◽

Sichen Li ◽

Yingjun Liu ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Treated Group ◽

Tube Formation ◽

Negative Control ◽

Vascular Endothelial ◽

Aneurysm Neck ◽

Endothelial Growth Factor

OBJECTIVEEmerging evidence shows that frequent recurrence of intracranial aneurysms (IAs) after endovascular coiling is attributable to the lack of endothelialization across the aneurysm neck. Recently, much attention has been given to the role of microRNAs (miRs) in vascular disease, although their contributory role to IA is poorly understood.METHODSAdult male Sprague-Dawley rats were subjected to microsurgery to create a coiled embolization aneurysm model, and were injected with miR-31a-5p agomir or a negative control agomir via the tail vein at a dose of 10 mg/kg per week for 4 weeks after IA induction. H & E staining, scanning electron microscopy, and flow cytometry were performed to evaluate the effects of miR-31a-5p agomir on endothelialization and the number of circulating endothelial progenitor cells (EPCs). The effects of miR-31a-5p on the viability and functioning of EPCs were also determined using Cell Counting Kit–8, wound-healing assay, and tube formation assays.RESULTSThe authors tested the ability of miR-31a-5p to promote EPC-induced endothelialization in a model of coiled embolization aneurysm. miR-31a-5p agomir improved endothelialization and elevated the number of circulating EPCs in the peripheral blood compared to a negative control agomir–treated group. In addition, the number of vWF- and KDR-positive cells in the aneurysm neck was increased in the miR-31a-5p agomir–treated group. Furthermore, upregulation of miR-31a-5p promoted EPC proliferation, migration, and tube formation and enhanced the expression of the proangiogenic factor vascular endothelial growth factor in vitro. Mechanistically, miR-31a-5p directly targeted the 3′ untranslated region (3′UTR) of Axin1 messenger RNA and repressed its expression. Besides, miR-31a-5p exerted its effect on EPCs by regulating the Axin1-mediated Wnt/β-catenin pathway.CONCLUSIONSCollectively, these results indicate that miR-31a-5p is an important regulator of EPC mobilization and endothelialization and may have a positive effect on aneurysm repair.

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Differential effects of cilostazol and pentoxifylline on vascular endothelial growth factor in patients with intermittent claudication

Clinical Science ◽

10.1042/cs1010305 ◽

2001 ◽

Vol 101 (3) ◽

pp. 305-311 ◽

Cited By ~ 14

Author(s):

Tsung-Ming LEE ◽

Sheng-Fang SU ◽

Chang-Her TSAI ◽

Yuan-The LEE ◽

Shoei-Shen WANG

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Intermittent Claudication ◽

Exercise Tolerance ◽

Treated Group ◽

Walking Distance ◽

Diabetic Patients ◽

Vascular Endothelial ◽

Positive Direction ◽

Endothelial Growth Factor

Cilostazol is a new phosphodiesterase inhibitor with anti-platelet and vasodilatory properties. Cilostazol and pentoxifylline are the only two drugs that have been approved for the treatment of patients with intermittent claudication. However, the mechanisms by which exercise tolerance is improved remain unclear. Vascular endothelial growth factor (VEGF) is a potent endothelial mitogen that results in angiogenesis when overexpressed in human subjects. To assess the potential role of VEGF in the improvement in exercise tolerance, we investigated plasma levels of VEGF in 50 patients with intermittent claudication who were allocated randomly to groups receiving cilostazol (n = 17), pentoxifylline (n = 17) or placebo (n = 16). Patients given either cilostazol or pentoxifylline showed a significant improvements in maximal walking distance compared with the placebo group (34 m and 33 m respectively, compared with 5 m; both P < 0.05). Neither cilostazol nor pentoxifylline increased the ankle-brachial index after treatment. Circulating VEGF levels were increased (from 116±29 to 169±45 pg/ml; P = 0.002), and the levels of VEGF were correlated significantly with exercise tolerance in a positive direction (r = 0.88, P = 0.004), in those patients treated with cilostazol that did not have diabetes mellitus. In contrast, VEGF levels remained stable after the administration of pentoxifylline. These findings suggest that VEGF may contribute to the cilostazol-related improvement in exercise tolerance in non-diabetic patients. However, pentoxifylline did not affect VEGF levels, although a similar improvement in maximal walking distance was achieved. Thus the mechanisms involved in the pentoxifylline-treated group were different from those in the cilostazol-treated group, and require further study.

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The effect of methenamine on vascular development: Experimental investigation using in vivo and insilico methods

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v13i8.7497 ◽

2020 ◽

Author(s):

Hadi Tavakkoli ◽

Masoud Imani ◽

Seyyed Mohammad Rahchamani ◽

Mohsen Rezvani

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Vascular Development ◽

Chorioallantoic Membrane ◽

Treated Group ◽

Inhibitory Effect ◽

Control Group ◽

Vascular Endothelial ◽

Endothelial Growth Factor

Background: Methenamine is a worldwide antibacterial agent for urinary system infections in human and animals. The effect of methenamine consumption during early phase of pregnancy is not fully clarified in previous studies. Vascular development is the essential part of the early embryonic growth. Objective: In this study, we used chicken chorioallantoic membrane to evaluate the effects of methenamine administration on angiogenesis process as a model. Materials and Methods: In this experimental study, 20 Ross 308 eggs (mean weight 55 ± 4) were incubated. The eggs were divided into two equal groups (n = 10/each). In the first group, methenamine (150 mg/kg egg weight) was injected on the shell membrane, and in the second group (control group) phosphate-buffered saline as injected. Methenamine was inoculated at 96 and 120 hr after incubation; 24 hr after the last inoculation, the eggs were removed and the egg’s shell was incised. Then, the development of vascular network and vascular endothelial growth factor A expression was evaluated. Results: Angiogenesis was significantly decreased after methenamine treatment. The indexes such as areas containing vessels, the vessels’ length, the percentage of angiogenesis developing areas, and vascular complexity in the treatment group receiving methenamine were significantly reduced compared to the control group. Vascular endothelial growth factor A expression was suppressed in the methenamine treated group. Conclusion: According to the achieved results, it was defined that methenamine could have an inhibitory effect on the growth and development procedures of extraembryonic vasculature. Key words: Methenamine, Angiogenesis modulating agents, Vascular endothelial growth factor A, Extraembryonic membranes.

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Abstract 3302: Vascular Endothelial Growth Factor Receptor Inhibition Impairs Intracerebral Hemorrhage-induced angiogenesis

Stroke ◽

10.1161/str.43.suppl_1.a3302 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Han-Jin Cui ◽

Qi-Ting Liu ◽

Hua-Jun Zhou ◽

TAO TANG

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Intracerebral Hemorrhage ◽

Growth Factor Receptor ◽

Treated Group ◽

Vegf Receptor ◽

Vascular Endothelial ◽

Sham Control ◽

Receptor Inhibition ◽

Endothelial Growth Factor

Background and purpose: Our previous work has proved that Intracerebral hemorrhage (ICH) induces angiogenesis, accompanied by upregulation of vascular endothelial growth factor (VEGF) and its receptors. As the most potent mitogen of endothelial cells (ECs), VEGF must bind to its receptor_vascular endothelial growth factor receptor-2, to make it be phosphorylated, which plays the roles in promoting proliferation, migration, survival of ECs. In this study, our purpose is to investigate the effect of VEGF receptor inhibition on angiogenesis after ICH. Method: Fifteen Kunming mice were randomly divided into 3 groups, including sham control (n=5), ICH group (n=5), and SU5416-treated group (n=5). ICH model was induced by injection collagenase type VII into right globus pallidus stereotaxically. SU5416-treated group was injected by SU5416 (10 mg/kg per dose) intraperitoneally after ICH induction. Intraperitoneal injection of 5-bromo-2'-deoxyuridine (BrdU) was used to label new-born ECs. Neurological severity score (NSS), corner turn test and foot-fault test were used to investigate the neurological function at 1d, 3d and 7d following the surgery. Angiogenesis and the level of p-VEGFR-2 were evaluated at 7d by immunohistochemistry. Results: At 1d, there is no difference between the two ICH-induced groups in NSS, corner turn test, foot-fault test; at 3d and 7d, the NSS in ICH group is significantly lower than that of SU5416-treated group ( P <0.05), and the times for right-turn and foot-fault in ICH group are notably fewer than those of SU5416-treated group ( P <0.05). At 7d, no expression of p-VEGFR-2 was detected in sham control animals, while the expression of p-VEGFR-2 in ICH group is notably higher than that in SU5416-treated group ( P <0.05); and the expression of p-VEGFR-2 is located in vWF-immunoreactive ECs; there is no BrdU-labeled nuclear in vessels observed in sham-control mice, but BrdU-labeled nuclei in vessels in ICH group are remarkably more than those in SU5416-treated group ( P <0.05). Conclusions: Activation of VEGFR-2 is an important mechanism for angiogenesis after ICH, which is related with the recovery of neurological behavioral function.

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Gamma-irradiated β-glucan modulates signaling molecular targets of hepatocellular carcinoma in rats

Tumor Biology ◽

10.1177/1010428317708703 ◽

2017 ◽

Vol 39 (8) ◽

pp. 101042831770870 ◽

Cited By ~ 2

Author(s):

Sawsan M Elsonbaty ◽

Walid E Zahran ◽

Fatma SM Moawed

Keyword(s):

Hepatocellular Carcinoma ◽

Vascular Endothelial Growth Factor ◽

Growth Factors ◽

Growth Factor ◽

Biological Response ◽

Treated Group ◽

Vascular Endothelial ◽

Extracellular Signal Regulated Kinase ◽

Extracellular Signal ◽

Endothelial Growth Factor

β-glucans are one of the most abundant forms of polysaccharides known as biological response modifiers which influence host’s biological response and stimulate immune system. Accordingly, this study was initiated to evaluate irradiated β-glucan as a modulator for cellular signaling growth factors involved in the pathogenesis of hepatocellular carcinoma in rats. Hepatocellular carcinoma was induced with 20 mg diethylnitrosamine/kg BW. Rats received daily by gastric gavage 65 mg irradiated β-glucan/kg BW. It was found that treatment of rats with diethylnitrosamine induced hepatic injury and caused significant increase in liver injury markers with a concomitant significant increase in both hepatic oxidative and inflammatory indices: alpha-fetoprotein, interferon gamma, and interleukin 6 in comparison with normal and irradiated β-glucan–treated groups. Western immunoblotting showed a significant increase in the signaling growth factors: extracellular signal–regulated kinase 1 and phosphoinositide 3-kinase proteins in a diethylnitrosamine-treated group while both preventive and therapeutic irradiated β-glucan treatments recorded significant improvement versus diethylnitrosamine group via the modulation of growth factors that encounters hepatic toxicity. The transcript levels of vascular endothelial growth factor A and inducible nitric oxide synthase genes were significantly higher in the diethylnitrosamine-treated group in comparison with controls. Preventive and therapeutic treatments with irradiated β-glucan demonstrated that the transcript level of these genes was significantly decreased which demonstrates the protective effect of β-glucan. Histological investigations revealed that diethylnitrosamine treatment affects the hepatic architecture throughout the significant severe appearance of inflammatory cell infiltration in the portal area and congestion in the portal vein in association with severe degeneration and dysplasia in hepatocytes all over hepatic parenchyma. The severity of hepatic architecture changes was significantly decreased with both β-glucan therapeutic and preventive treatments. In conclusion, irradiated β-glucan modulated signal growth factors, vascular endothelial growth factor A, extracellular signal–regulated kinase 1, and phosphatidylinositol-3-kinase, which contributed to experimental hepatocarcinogenesis.

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