Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), is a potent microvascular permeability enhancing cytokine and a selective mitogen for endothelial cells. It has been implicated in tumor angiogenesis and ascites fluid accumulation. Since development of the destructive synovial pannus in rheumatoid arthritis (RA) is associated with changes in vascular permeability (synovial fluid accumulation), synovial cell hyperplasia, and angiogenesis, we examined synovial fluids (SFs) and joint tissue for the expression and local accumulation of VPF/VEGF. VPF/VEGF was detected in all of 21 synovial fluids examined and when measured by an immunofluorimetric assay, ranged from 6.9 to 180.5 pM. These levels are biologically significant, since < 1 pM VPF/VEGF can elicit responses from its target cells, endothelial cells. Levels of VPF/VEGF were highest in rheumatoid arthritis fluids (n = 10), with a mean value (+/- SEM) of 59.1 +/- 18.0 pM, vs. 21.4 +/- 2.3 pM for 11 SFs from patients with other forms of arthritis (p = 0.042). In situ hybridization studies that were performed on joint tissues from patients with active RA revealed that synovial lining macrophages strongly expressed VPF/VEGF mRNA, and that microvascular endothelial cells of nearby blood vessels strongly expressed mRNA for the VPF/VEGF receptors, flt-1 and KDR. Immunohistochemistry performed on inflamed rheumatoid synovial tissue revealed that the VPF/VEGF peptide was localized to macrophages within inflamed synovium, as well as to microvascular endothelium, its putative target in the tissue. Together, these findings indicate that VPF/VEGF may have an important role in the pathogenesis of RA.
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PMID:Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue. 800 92

Granulosa cells in the ovulatory follicle express messenger ribonucleic acid encoding vascular endothelial growth factor (VEGF), an agent that may mediate the neovascularization of the developing corpus luteum, but it is not known whether luteinizing granulosa cells synthesize and secrete VEGF during the periovulatory interval. Studies were designed to evaluate the effects of an in vivo gonadotropin surge on VEGF production by macaque granulosa cells (study 1) and to test the hypothesis that gonadotropins act directly on granulosa cells to regulate VEGF production (study 2). Monkeys received a regimen of exogenous gonadotropins to promote the development of multiple preovulatory follicles. Nonluteinized granulosa cells (i.e. preovulatory; NLGC) and luteinized granulosa cells (i.e. periovulatory; LGC) were aspirated from follicles before and 27 h after an ovulatory gonadotropin bolus, respectively. Cells were either incubated for 24 h in medium with or without 100 ng/mL hCG (study 1) or cultured for 6 days in medium with or without 100 ng/mL hCG or 0.1, 1, 10, and 100 ng/mL of recombinant human LH (r-hLH) or r-hFSH (study 2). Culture medium was assayed for VEGF and progesterone. In study 1, LGC produced 8-fold greater levels of VEGF than NLGC (899 +/- 471 vs. 111 +/- 26 pg/mL, mean +/- SEM; P < 0.05). In vitro treatment with hCG increased (P < 0.05) VEGF production by NLGC to levels that were not different from the LGC incubated under control conditions. In vivo bolus doses of r-hCG (100 and 1000 IU) and r-hFSH (2500 IU) were equally effective in elevating granulosa cell VEGF production. In study 2, in vitro treatment with r-hFSH, r-hLH, and hCG markedly increased (P < 0.05) VEGF and progesterone production by the NLGC in a dose- and time-dependent manner. By comparison, the three gonadotropins (100 ng/mL dose) only modestly increased VEGF and progesterone production by LGC. These experiments demonstrate a novel role for the midcycle surge of gonadotropin (LH/CG or FSH) in primates to promote VEGF production by granulosa cells in the periovulatory follicle. Further, the data demonstrate that FSH-like as well as LH-like gonadotropins directly stimulate VEGF synthesis by granulosa cells.
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PMID:Follicle-stimulating hormone and luteinizing hormone/chorionic gonadotropin stimulation of vascular endothelial growth factor production by macaque granulosa cells from pre- and periovulatory follicles. 921 84

Angiogenesis plays a key role in solid tumor growth. The purpose of this work was to study angiogenesis in acute myeloid leukemia (AML). We stained bone marrow samples from 20 adult patients with untreated AML and 20 normal controls using endothelial cell markers (ULEX-E and von Willebrand factor [vWF]). The number of vessels per millimeter length of bone marrow core biopsy specimen was scored by light microscopy. Using ULEX-E staining, AML marrows had (average +/- SEM) 8.3 +/- 3.6 vessels/mm (range, 3.7-19.3), whereas normal marrows had 4.3 +/- 1.8 vessels/mm (range, 1.6-7.9). A similar difference was noted using vWF staining (8.6 +/- 3.0 vessels/mm vs 4. 9 +/- 2.2 vessels/mm in AML vs normal bone marrows, respectively). The differences between the numbers of vessels/mm in AML and normal marrows were highly significant (P <.0001 for both ULEX-E and vWF staining). When analyzed by FAB category, there was no difference in the average number of vessels/mm among the different subgroups of AML. Using reverse transcriptase polymerase chain reaction, we observed that the HL-60 and U937 human AML cell lines and 4 of 4 freshly isolated AML cells from untreated patients expressed mRNA for vascular endothelial growth factor (VEGF). Both cell lines as well as all fresh AML isolates tested expressed VEGF protein. Basic fibroblast growth factor was expressed only in HL-60 cells and in only 3 of 4 fresh AML samples. These observations suggest that angiogenesis may play a role in the pathogenesis of AML. Inhibition of angiogenesis could constitute a novel strategy for the treatment of AML. (Blood. 2000;95:309-313).
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PMID:Evidence of increased angiogenesis in patients with acute myeloid leukemia. 1118 59

Angiogenesis is of prognostic importance not only in solid tumors but also in malignant blood diseases. We measured levels of vascular endothelial growth factor (VEGF), angiogenin (ANG), and basic fibroblast growth factor (bFGF) in peripheral blood samples from 65 patients with myelodysplastic syndrome (MDS), from 25 patients with de novo acute myeloid leukemia (AML), and from 50 healthy donors. In matched samples, VEGF levels in serum were substantially higher than VEGF levels in plasma (380.7 +/- 56 pg/ml vs. 45.3 +/- 4.5 pg/ml, mean +/- SEM, p < 0.001), whereas serum and plasma levels of ANG were comparable and significantly correlated (r = 0.8; p < 0.01). Compared to normal controls (1.3 +/- 0.09 pg), serum levels of VEGF corrected for the peripheral blood platelet count (VEGF/10(6) platelets, VEGF(PLT)) were elevated in patients with refractory anemia (RA; 3.1 +/- 0.8 pg, p < 0.01), and reached maximal values in patients with advanced stage MDS (RAEB, RAEB-t) (3.5 +/- 0.6 pg, p < 0.001), de novo AML (3.6 +/- 1.1 pg, p < 0.05), and chronic myelomonocytic leukemia (CMML; 3.7 +/- 0.9 pg; p < 0.001). Levels of soluble ANG were elevated in RA (351 +/- 25.7 ng/ml, p < 0.001), in RAEB/RAEB-t (402 +/- 17.9 ng/ml; p < 0.001), in CMML (413.8 +/- 29.5 ng/ml; p < 0.001), and in patients with AML (305.1 +/- 17.1 ng/ml; p < 0.01, controls 255.4 +/- 8.1 ng/ml). Serum bFGF was neither elevated in MDS nor in AML patients. These results suggest that VEGF(PLT) is a marker of disease progression in MDS. Moreover, we show for the first time that elevated blood levels of ANG can be found in patients with myeloid malignancies, suggesting a role of ANG in the pathogenesis of these diseases.
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PMID:Blood levels of angiogenin and vascular endothelial growth factor are elevated in myelodysplastic syndromes and in acute myeloid leukemia. 1184 8

We have previously shown that inhibition of nitric oxide generated by inducible nitric oxide synthase (iNOS) results in impaired colon anastomotic healing. Therefore, we proceeded to assess whether disruption of iNOS activity alters the normal pattern of growth factor expression during anastomotic healing. Two groups of male Sprague-Dawley rats underwent distal colonic division and anastomosis, jugular venous catheterization and subcutaneous placement of polyvinyl alcohol sponges. The first group (n = 10) received q8 hour intravenous injections of 10 mg/kg L-N-iminoethyl-lysine (L-NIL, a selective inhibitor of iNOS), while the second group (n = 12) received equal volumes of saline. On postoperative day 5, animals were sacrificed and anastomotic bursting pressure was determined. Histologic sections of the anastomosis were subjected to in situ hybridization versus mRNA of the proteins listed below. Positive controls were reacted with a poly-thymidine (poly-T) probe versus ubiquitous mRNA poly-adenine tails. Positively stained cells were quantified using a calibrated optical grid encompassing 0.5 mm(2) area centered over the anastomosis. Results are reported as the number of positive cells per 1000 cells positive for poly-T. L-NIL treated animals demonstrated an 18% decrease in wound fluid NO(X) compared to controls (29.2 +/- 1.2 vs. 34.6 +/- 2.0 microM, mean +/- SEM; P = 0.035). This corresponded to a 17% decrease in anastomotic bursting pressure (153 +/- 4 vs. 182 +/- 8 mm Hg, mean +/- SEM; P < 0.05). L-NIL also markedly increased the number of cells expressing transforming growth factor-beta, tumor necrosis factor-alpha, vascular endothelial growth factor, and both inducible and endothelial forms of nitric oxide synthase. L-NIL had no effect on the expression of basic fibroblast growth factor. The data demonstrate that iNOS inhibition markedly disrupts the profile of cytokine and growth factor mRNA normally expressed during anastomotic healing. This provides in vivo evidence that NO modulates gene expression during anastomotic healing.
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PMID:Modulation of growth factor and cytokine expression by nitric oxide during rat colon anastomotic healing. 1265 65

Non-Hodgkin's lymphomas (nHL) is a heterogenous group of lymphoid malignancies with different patterns of behaviour and response to treatment. International Prognostic Index (IPI) is commonly used to predict outcome of treatment in nHL. There are several reports that vascular endothelial growth factor (VEGF), the most potent inducer of angiogenesis, may have prognostic significance in nHL. The aim of the study was to evaluate the serum level of VEGF as a marker of angiogenesis in 35 patients with B-cell nHL compared with control group of 14 healthy people. Moreover, in nHL group VEGF serum level was correlated with IPI risk factors. VEGF serum level was evaluated by ChemiKine sandwich ELISA kit (Chemicon International). VEGF serum level was significantly higher in nHL group than in the control, 193.78 pg/ml +/- 6.82 SEM and 31.51 +/- 1.67 SEM respectively. In nHL group a positive correlation was found between increased VEGF serum level and serum lactate dehydrogenase level. The levels of VEGF were not significantly different in agressive or indolent nHL patients. VEGF serum level is increased in active lymphoma. This observation may have prognostic and clinical significance and provides rationale for use antiangiogenic agents in nHL therapy.
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PMID:[Vascular endothelial growth factor (VEGF) serum concentration in non-Hodgkin's lymphoma patients]. 1567 66

Von Hippel-Lindau (VHL) gene is a tumor suppressor gene that plays a genome "gatekeeper'' role and controls several downstream effector genes. We have previously demonstrated that both in vivo and in vitro adenovirus-mediated gene transfer of tumor suppressor genes into the vascular endothelium is effective in decreasing neointimal hyperplasia and abnormal cell proliferation. The degree of apoptosis induced by these genes is critical in mediating the in vivo responses to gene therapy and the maintenance of the crucial balance between cell death and viability. Since VHL gene is known to regulate vascular endothelial growth factor (VEGF) as well as other angiogenic factors, it may exhibit a greater potential in the attenuation of vascular disorders in comparison to other tumor suppressor genes. This study focused on whether adenovirus-mediated VHL gene transfer into human vascular smooth muscle cells has an effect on cell proliferation and induction of apoptosis. Human aortic smooth muscle cells (HASMC) were grown as monolayers and transfected with varying titers of adenovirus containing the VHL cDNA (AdVHL). The negative controls were adenovirus containing green fluorescent protein (AdGFP), vector alone (AdNull), and virus-free infection medium. Adenovirus encoding wild-type p53 (Adp53) was used as positive control. Cell viability and proliferation were determined by using trypan blue exclusion and MTS-based CellTiter 96 AQ Proliferation Assay. Apoptosis was evaluated by TUNEL assay, morphologic changes, and nucleosomal DNA degradation. Following AdVHL transfection HASMCs demonstrated a dose-dependent decrease in viability as compared to negative controls (p < 0.05). AdVHL-transfected cells exhibited a decrease in their proliferative ability by 40.21 +/-1.66 (SEM)%. In cultures transfected with the positive control, Adp53, the cell viability as well as proliferation was highly reduced (p < 0.001). AdGFP and AdNull did not increase HASMC apoptosis above baseline levels. The cells exposed to adenoviruses expressing tumor suppressor genes underwent apoptosis, with Adp53 demonstrating a very high magnitude of cell death (75.27 +/-3.52 [SEM]%). AdVHL expression caused 45.36 +/-2.55 (SEM)% apoptosis in HASMC. Recombinant adenovirus-mediated VHL expression is efficacious in limiting vascular smooth muscle cell growth in vitro. Overexpression of VHL suppresses HASMC proliferation and regulates apoptosis. Further experiments are indicated to examine whether VHL may be a useful adjunct in limiting myointimal hyperplasia.
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PMID:The effect of von hippel-lindau gene transfer on human vascular smooth muscle cell proliferation and apoptosis. 1569 45

To elucidate the functional roles of Wnt5b in adipogenesis, we characterized gene expression profiles in Wnt5b overexpressing 3T3-L1 cells using microarray analysis. Of the approximately 20,000 genes screened, we found that 85 genes were up-regulated and 211 genes were down-regulated in 3T3-L1 cells overexpressing Wnt5b. Among the genes regulated by Wnt5b, the expressions of insulin like growth factor-1 (IGF-1), vascular endothelial growth factor-C (VEGF-C), and WNT1 inducible signaling pathway protein 1 (WISP-1), which were known to be up-regulated by Wnt1/beta-catenin signaling, were decreased in the Wnt5b overexpressing cells. This result was subsequently confirmed by real-time quantitative RT-PCR (IGF-1; 0.74+/-0.08 and 0.56+/-0.08, WISP-1; 0.71+/-0.03 and 0.56+/-0.08, and VEGF-C; 0.67+/-0.01 and 0.80+/-0.07, mean+/-SEM, compared with the control at zero and two days after induction of differentiation, respectively). We also found that Wnt5b overexpression in 3T3-L1 preadipocytes was able to partially prevent the inhibitory effect of Wnt3a on adipogenesis. Furthermore, the overexpression of Wnt5b was able to inhibit Wnt3a-induced activation of the canonical Wnt/beta-catenin pathway as evidenced by the reduced translocation of beta-catenin into the nucleus. These findings indicate that Wnt5b may promote adipogenesis in 3T3-L1 cells, at least in part, by antagonizing the canonical Wnt/beta-catenin pathway.
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PMID:Wnt5b partially inhibits canonical Wnt/beta-catenin signaling pathway and promotes adipogenesis in 3T3-L1 preadipocytes. 1579 11

The objective of this study was to assess the in vitro release kinetics and the in vivo angiogenic effect of human vascular endothelial growth factor (VEGF)-activated poly(DL-lactide-co-glycolide) (PLGA) sponge. The highly porous sponges (each 3 x 4 x 4 mm(3)) were activated by soaking in a VEGF solution (2.5 or 5.0 microg) and then freeze-drying. In vitro release in PBS was investigated by a competitive enzyme immunoassay for up to 3 weeks. The burst-type initial release within the first 3 days followed a more controlled one lasting for >2 weeks. The angiogenic potential of the VEGF sponge was evaluated by subcutaneous implantation into the epigastric groin fascia of Wistar rats. Histomorphometry and SEM confirmed the formation of new capillaries infiltrating the sponge pores starting from the first week and the drastic anostomosis at weeks 2 and 3. However, the rats implanted with control sponges or receiving VEGF injection exhibited much lower or no angiogenic response, respectively. TEM revealed the neo-vessels had a single endothelial layer surrounded by the matrix inoculated with the rat circulation. The results indicate that VEGF-activated PLGA sponge can be considered as a tool to establish neovascularized subcutaneous transplantation sites for tissue-engineering applications.
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PMID:Localized angiogenesis induced by human vascular endothelial growth factor-activated PLGA sponge. 1667 7

Progenitor cell plasticity enhances positive remodeling of damaged tissue. We and others have previously shown that progenitor cells may limit apoptosis and modulate inflammation in part by the production of growth factors. However, recent studies suggest that progenitor cells senesce and lose their differentiation potential with increasing time in culture and passage. We hypothesize that murine bone marrow mesenchymal stem cells (MSCs) are cardioprotective against ischemia/reperfusion injury in the isolated perfused rat heart, and that passage number has an adverse effect on MSC activation and cardioprotection. Adult male and female Sprague-Dawley rat hearts were isolated, perfused via Langendorff model, and subjected to ischemia/reperfusion. Mouse MSCs were harvested, cultured, suspended in perfusate, and infused before global index ischemia. Hearts were assigned to controls or infusion with passage 3, 5, or 10 MSCs. In addition, MSCs in culture were stressed by hypoxia and increasing doses of endotoxin (lipopolysaccharide). Mesenchymal stem cell activation was determined by measuring vascular endothelial growth factor production with enzyme-linked immunosorbent assay. All data are reported as mean +/- SEM and were analyzed with 2-way analysis of variance. Differences are considered significant if P < 0.05. Passage 3 murine MSC infusion in hearts before ischemia reduced the depression of left ventricular developed pressure, attenuated the increase of end-diastolic pressure, and reduced the depression of +dP/dT and -dP/dT. However, the MSC protective effect disappeared in hearts infused with passage 5 and passage 10 MSCs. Although hypoxia and lipopolysaccharide resulted in significant activation of MSCs, passage 3 MSCs demonstrated significantly greater vascular endothelial growth factor release than passage 5 and 10 MSCs. Acute murine MSC infusion confers protection in isolated rat hearts. However, high passage number has an adverse effect on MSC activation and protection. This portends limited ex vivo expansion before possible therapeutic use.
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PMID:High passage number of stem cells adversely affects stem cell activation and myocardial protection. 1711 32


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