The sFLT-1 to PlGF Ratio is Impaired in Patients with Thalassemia and Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2010-2010 ◽  
Author(s):  
Ioannis Papassotiriou ◽  
Alexandra Kouraklis-Symeonidis ◽  
Filia Apostolakou ◽  
Athanassios Akalestos ◽  
Vlassis Vlazakis ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Control Group ◽  
Vascular Endothelial ◽  
Cell Disease ◽  
Group A ◽  
Endothelial Growth Factor ◽  
Plgf Ratio

Abstract Abstract 2010 Poster Board I-1032 Background: Placental growth factor (PlGF) is a member of the vascular endothelial growth factor family and is associated with inflammation and with pathologic angiogenesis. PlGF is released from marrow erythroid cells. Serum PlGF concentrations have been reported to be elevated in patients with sickle cell disease. The fms-like tyrosine kinase-1 or sFlt-1 is a soluble form of vascular endothelial growth factor receptor-1 (VEGF-R1), which binds to and sequesters circulating free vascular endothelial growth factor (VEGF) and free PlGF, thereby neutralizing their pro-angiogenic effects. PlGF and VEGFR-1 are key molecules in regulating the angiogenic switch during pathological conditions maintaining the proangio-and anti-angiogenic balance. Perturbations of this balance leads to various degree of endothelial dysfunction, a common pathology in patients with hemoglobinopathies and specifically induce pulmonary hypertension (PHT). In this study we assessed the PlGF and sFLT-1 levels in patients with hemoglobinopathies at steady state. Patients and Methods: One hundred twenty three patients with hemoglobinopathies and 20 apparently healthy individuals were included in the study divided in groups as follows: Group A: 38 patients with thalassemia intermedia; Group B: 41 patients with transfusion-dependent beta-thalassemia; Group C: 33 patients with beta-thallassemia/sickle cell disease (SCD) Group D: 11 patients with beta-thallassemia and clinical evidence of PHT, and; Group E: 20 individuals served as control group In patients and controls we performed measurements of PlGF and sFLT-1 with fully automated electrochemiluminescence assays using the immunochemistry autoanalyzer Roche cobas e411. This method provides rapid and reliable assessments and follow-up of patients any time in the day compared to immunoenzymatic assays. Results: We found that: a) serum PlGF levels were increased in all groups of patients compared to controls (42.7±19.9 pg/mL, 49.9±23.4 pg/mL, 27.5±9.4 pg/mL, 58.1±27.6 pg/mL for group A, B, C and D, respectively vs 17.1±3.9 pg/mL for control group, p<0.001), b) serum sFLT-1 levels were also increased in all groups of patients compared to controls (89.3±18.3 pg/mL, 90.2±24.0 pg/mL, 89.4±15.3 pg/mL, 117.2±43.5 pg/mL, respectively vs 76.7±11.1 pg/mL, p<0.001 for control group and c) sFLT-1 to PlGF ratio was decreased in all groups of patients compared to controls (2.4±0.9, 2.2±1.2, 3.5±1.0, 2.2±0.8, respectively vs 4.7±1.1 for control group, p<0.001. The most significant changes were found in patients with PHT. Conclusions: These findings indicate that patients with thalassemia syndromes and SCD appear to have increased degree of angiogenesis, which is more pronounced in patients with thalassemia compared to patients with SCD and markedly increased in patients with PHT. The decreased sFLT-1/PlGF ratio in almost all patients suggest that the proangio-and anti-angiogenic system is shifted towards to proangiogenic state, providing evidence that patients with hemoglobinopathies even in the steady phase have altered angiogenic state and low-grade inflammation. The results are in accordance to those published earlier for SCD (Blood, 2008;112:856-865.), where the authors demonstrated that PlGF levels were intrinsically elevated due to the increased red cell turnover and may contribute to inflammation and PHT seen in the disease. Disclosures: No relevant conflicts of interest to declare.

Nitric Oxide and Vascular Endothelial Growth Factor during Pregnancy in Sickle Cell Disease

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4809-4809
Author(s):  
Julia E. Brittain ◽  
Kenneth I Ataga ◽  
Sean Lee ◽  
John M. Thorp ◽  
Eugene P. Orringer
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Sickle Cell Disease ◽  
Pregnancy Outcomes ◽  
Arginase Activity ◽  
Vascular Endothelial ◽  
Cell Disease ◽  
No Release ◽  
Endothelial Growth Factor

Abstract BACKGROUND: Vascular Endothelial Growth Factor (VEGF) is a multifunctional cytokine that may be clinically relevant in sickle cell disease (SCD). In additional to its role as a potent activator of angiogenesis, VEGF is also a potent inducer of Nitric Oxide (NO) release. Patients with SCD have impaired NO metabolism and decreased bioavailability of NO due to chronic hemolysis which may contribute to the vasculopathy that is present in this disorder. High levels of plasma arginase and the resultant decreased arginine/ornithine ratios have also been proposed to contribute to low NO levels in SCD patients. We have previously reported that pregnant SCD patients have higher circulating levels of the naturally occurring VEGF antagonist, sFLT-1, when compared to pregnant African American controls. High levels of sFLT-1 are associated with poor pregnancy outcomes including preeclampsia and delivery of small for gestational age (SGA) infants. OBJECTIVE: In this study we wanted to assess the levels of NO, free VEGF, sFLT-1 and arginase activity during pregnancy in SCD. We also sought to explore the relationship between NO and sFLT-1 with pregnancy outcome. METHODS: We performed an analysis of previously collected plasma/serum samples obtained from the Pregnancy, Infection and Nutrition (PIN) study cohort at UNC- Chapel Hill. Subjects were matched on race, gestational age, BMI and smoking status. Levels of free VEGF were quantified by luminex analysis and confirmed by ELISA. NO was quantified via its metabolite NOx using a modified Griess method in de-proteinated serum/plasma. Arginase activity was quantified by ELISA. Pregnancy outcomes were previously recorded by PIN study personnel. RESULTS: We found that levels of free VEGF and NO were significantly lower in pregnant women with SCD than in matched pregnant controls (VEGF: 5.8 pg/ml vs. 13.56 pg/ml, p = 0.03, NOx: 14.31 μM vs. 26.99 μM, p=0.0009). We also found a significant inverse correlation between NOx levels and sFLT-1 levels (r2=0.6421, p = 0.0094), but no relationship between NOx and arginase activity in plasma. There was also no difference in arginase activity between pregnant SCD subjects and controls. Finally, pregnant SCD subjects that delivered an SGA infant had significantly lower levels of NOx than those women that did not. CONCLUSIONS: These results suggest that VEGF may play a role in NO release during pregnancy in SCD. In addition, low NO levels may contribute to poor pregnancy outcomes in pregnant SCD women.

Effect of HylocereusPolyrhizus Rind Extract Toward Interleukin-1β, Vascular Endothelial Growth Factor Expression, Endometriosis Implant Area

2017 ◽  
Vol 9 (08) ◽  
Author(s):  
YanuarEka P. ◽  
Hendy Hendarto ◽  
Widjiati .
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Treatment Group ◽  
Negative Control Group ◽  
Negative Control ◽  
Control Group ◽  
Vascular Endothelial ◽  
Mice Model ◽  
Endothelial Growth Factor ◽  
Fruit Rind

Retrograde menstruation lead to I Kappa B Kinase (IKK) fosforilation in peritoneum macrophage and cause secretion of proinflammatory cytokine interleukin1β then stimulate endometriosis cell to produce Vascular Endothelial Growth Factor which lead to increasing of endometriosis lession seen as endometriosis implant area. Cytokine secretion was inhibited through prevention of NF-κB activation by dragon red fruit rind extract (Hylocereuspolyrhizus). The aim of this reserach is to know the effect of dragon red fuit rind extract with 0,25; 0,5; and 1 mg/g bodyweight dosage toward IL-1β, VEGF expression and implant area in endometriosis mice model. The design of this experiment was randomized post test only control group design.Endometrios mice model were made in 14 days and split into two group, positive control group and treatment group after two week negative control group and postive control group were given Na-CMC 0,5% solution consequetively, and treatment group were given dragon red fruit extract with different dosage. Signification number for IL-1β is p>0,05, signification number for VEGF is p>0,05, and implant area signification number is p>0,05. Administration of dragon red fruit rind extract can decrease IL-1β, VEGF, and implant area.

scholarly journals Vascular endothelial growth factor in prognosis of splenic malignant tumours in dogs

2014 ◽  
Vol 58 (2) ◽  
pp. 255-260
Author(s):  
Aleksandra Sobczyńska-Rak ◽  
Izabela Polkowska ◽  
Adam Brodzki
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Comparative Analysis ◽  
Growth Factor ◽  
Who Classification ◽  
Control Group ◽  
Vascular Endothelial ◽  
Malignant Tumours ◽  
Blood Samples ◽  
Endothelial Growth Factor ◽  
Immunoenzymatic Assays

Abstract The aim of the study was to determine the levels of the vascular endothelial growth factor (VEGF) in the serum of dogs suffering from splenic malignant tumours, prior to splenectomy, as well as three and six months after the surgery. Tumours and blood samples were collected from 10 dogs of various breeds, aged between 7 and 13 years, and from 10 control animals. Tumour sections were fixed in 10% buffered formalin for 24 h. The type of tumour was determined according to the WHO classification. Blood samples were centrifuged and the obtained sera were subjected to immunoenzymatic assays to determine the VEGF levels. The median of VEGF levels in the serum of dogs suffering from splenic malignant tumours was 37.85 pg/mL (15.40-107.18 pg/mL). The highest values were observed in dogs with confirmed metastases (107.18 pg/mL and 65.43 pg/mL). The VEGF values in control group were between 0.1 pg/mL and 13.04 pg/mL. A comparative analysis of the VEGF levels against the animals' survival time indicated that VEGF overexpression may serve as a prognostic factor in cases of malignant tumours of the spleen.

Expression of Vascular Endothelial Growth Factor, Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 in Polycystic Ovarian Syndrome Rats and Its Implication

2021 ◽  
Vol 11 (5) ◽  
pp. 841-846
Author(s):  
Wei Li ◽  
Yufang Zhang ◽  
Fuping Li ◽  
Yufen Shi ◽  
Yan Wang
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Matrix Metalloproteinase ◽  
Polycystic Ovary ◽  
Ovarian Tissue ◽  
Matrix Metalloproteinase 2 ◽  
Control Group ◽  
Vaginal Smear ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

Polycystic ovary syndrome (PCOS) is a female endocrine disorder and frequently leads to infertility. Vascular endothelial growth factor (VEGF) has crucial roles and matrix metalloproteinase (MMPs) is correlated with cell migration. Both of them are involved in the occurrence and progression of PCOS. This study established a rat PCOS model using letrozole to measure the expression of VEGF, MMP-2 and MMP-9 (MMP-2/9), to analyze its correlation with PCOS. Letrozole was applied by gavage to establish rat PCOS model. General condition and ovarian tissue morphology were observed under a light field microscope. ELISA and immunohistochemistry (IHC) were used to detect serum or tissue expression of VEGF, MMP-2/9. Estrous cycle of rats was disrupted after 12 d for using letrozole. Vaginal smear showed abundant leukocytes with sparse keratinocytes. Ovary showed whitening and increased volume, with early phase small follicles plus lower granular cells or corpus luteum. Compared to control group, experimental group had significantly higher VEGF, MMP-2/9 (P < 0.05), which were higher in antral follicles than those in preantral follicle with higher expressions than primordial follicle (P < 0.05). In conclusion, VEGF, MMP-2/9 are abundantly expressed in both serum and tissues of PCOS rats.

Abstract 1066: Ultrasound-targeted Plasmid Delivery of Vascular Endothelial Growth Factor and Angiopoietin-1: Combination Gene Therapy for Therapeutic Angiogenesis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Alexandra H Smith ◽  
Michael A Kuliszewski ◽  
Hiroko Fujii ◽  
Duncan J Stewart ◽  
Jonathan R Lindner ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Plasmid Dna ◽  
Therapeutic Angiogenesis ◽  
Blood Velocity ◽  
Control Group ◽  
List Type ◽  
Vascular Endothelial ◽  
Time Points ◽  
Endothelial Growth Factor

We have previously shown that ultrasound-mediated (UM) delivery of vascular endothelial growth factor (VEGF) plasmid-bearing microbubbles promotes therapeutic angiogenesis. While VEGF is important during the initiation of angiogenesis, it results in primarily immature vessels, which are prone to late regression. Angiopoietin (Ang)-1 is a potent growth factor that acts to stabilize the neovasculature, later in the angiogenic process. We hypothesized that temporal delivery of VEGF and Ang-1 plasmid DNA would result in a more sustained angiogenic response, as compared to VEGF alone, in the setting of severe chronic ischemia. Methods : Unilateral hindlimb ischemia was produced by iliac artery ligation in 30 rats. At day 14 post-ligation, microvascular blood velocity (β) and flow (MBF) in the proximal hindlimb muscles were assessed by contrast-enhanced ultrasound (CEU). UM-delivery of plasmid (500 μg cDNA)-bearing microbubbles (1×109), was then performed at pre-specified time points, with treatment groups including VEGF alone at day 14; VEGF at day 14 followed by Ang-1 at day 28; and control rats receiving no therapy (n=10 per group). β and MBF were re-assessed at day 28 and 8 wks post-ligation. Results : Relative MBF (normalized to the contralateral normal leg) remained reduced at all time points after ligation in the control group. In VEGF-alone treated animals, MBF in the ischemic leg increased 2 wks after delivery (0.48 ± 0.19 to 0.82 ± 0.23, p < 0.001), but regressed over the next 4 wks (0.61 ± 0.14 at 8 wk, NS vs. 2 wks). In the VEGF/Ang-1 treated animals, MBF in the ischemic leg also increased 2 weeks after VEGF delivery (0.39 ± 0.19 to 0.69 ± 0.28, p < 0.01); however, vascular regression was prevented by late Ang1 delivery (0.83 ± 0.20 at 8 wks, p < 0.005 vs. 2 wks and p<0.01 vs VEGF alone at 8 wks). At week 8, relative β values were greater in VEGF/Ang-1 treated compared to VEGF-alone treated animals (0.87 ± 0.33 to 0.60 ± 0.23, p < 0.05). Conclusions : Compared to delivery of VEGF alone, delivery of Ang-1 plasmid DNA at 2 wks post-VEGF gene delivery results in sustained improvement in MBF, with prevention of late vascular regression. The greater microvascular blood velocity in VEGF/Ang-1 treated muscle may signify improved vascular functionality with late Ang-1 therapy.

scholarly journals Large adipose tissue generation in a mussel-inspired bioreactor of elastic–mimetic cryogel and platelets

2018 ◽  
Vol 9 ◽  
pp. 204173141880863 ◽  
Author(s):  
Qiang Chang ◽  
Junrong Cai ◽  
Ying Wang ◽  
Ruijia Yang ◽  
Malcolm Xing ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Adipose Tissue ◽  
Growth Factor ◽  
Cellular Proliferation ◽  
Platelet Derived Growth Factor ◽  
Control Group ◽  
Vascular Endothelial ◽  
Angiogenic Growth Factors ◽  
Congenital Deformities ◽  
Endothelial Growth Factor

Soft tissue generation, especially in large tissue, is a major challenge in reconstructive surgery to treat congenital deformities, posttraumatic repair, and cancer rehabilitation. The concern is along with the donor site morbidity, donor tissue shortage, and flap necrosis. Here, we report a dissection-free adipose tissue chamber–based novel guided adipose tissue regeneration strategy in a bioreactor of elastic gelatin cryogel and polydopamine-assisted platelet immobilization intended to improve angiogenesis and generate large adipose tissue in situ. In order to have matched tissue mechanics, we used 5% gelatin cryogel as growth substrate of bioreactor. Platelets from the platelet-rich plasma were then immobilized onto the gelatin cryogel with the aid of polydopamine to form a biomimetic bioreactor (polydopamine/gelatin cryogel/platelet). Platelets on the substrate led to a sustained high release in both platelet-derived growth factor and vascular endothelial growth factor compared with non-polydopamine-assisted group. The formed bioreactor was then transferred to a tissue engineering chamber and then inserted above inguinal fat pad of rats without flap dissection. This integrate strategy significantly boomed the vessel density, stimulated cellular proliferation, and upregulated macrophage infiltration. There was a noticeable rise in the expression of dual-angiogenic growth factors (platelet-derived growth factor and vascular endothelial growth factor) in chamber fluid; host cell migration and host fibrous protein secretion coordinated with gelatin cryogel degradation. The regenerated adipose tissue volume gained threefold larger than control group (p < 0.05) with less fibrosis tissue. These results indicate that a big well-vascularized three-dimensional mature adipose tissue can be regenerated using elastic gel, polydopamine, platelets, and small fat tissue.

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