Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular endothelial growth factor (VEGF) plays a crucial role in the pathogenesis of inflammatory joint disease, including angiogenesis and synovitis. Rheumatoid arthritis is a chronic inflammatory disease characterized by progressive synovitis and subsequent bone destruction mediated by osteoclasts (OCs). In this study, we investigate the effects of VEGF on OC precursor cells (pOCs) using Raw cells and adjuvant-induced arthritis in rats. OCs and pOCs in the arthritic joints express VEGF and VEGF receptor type I (Flt-1). Raw cells also express Flt-1, and VEGF treatment stimulated chemotaxis, cell proliferation, the association of Flt-1 with focal adhesion kinase (FAK), and the tyrosine phosphorylation of FAK in Raw cells. The tyrosine phosphorylation of FAK was also observed in pOCs in the arthritic joints of adjuvant-induced arthritis. Adenovirus-mediated expression of FAK-related nonkinase in Raw cells inhibited the effects of VEGF in a dominant negative manner. Furthermore, intra-articular injection of the FAK-related nonkinase virus suppressed the recruitment of pOCs and bone destruction. Our results suggest the possible involvement of the VEGF-Flt-1-FAK pathway in inflammatory disease-induced joint destruction.
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PMID:Possible involvement of the vascular endothelial growth factor-Flt-1-focal adhesion kinase pathway in chemotaxis and the cell proliferation of osteoclast precursor cells in arthritic joints. 1202 86

Vascular endothelial growth factor (VEGF) induces increased vessel permeability and formation of abnormal vessels. To investigate cerebral blood flow (CBF) during local overexpression of VEGF recombinant adenoviruses carrying the human VEGF165 complementary DNA (2.3 to 23. 108 pfu/mL) were injected stereotactically into the caudate nucleus of anesthetized rats. Saline and adenoviruses carrying the beta-galactosidase gene served as controls. Eleven days later (1) size and density of vessels were assessed in hematoxylin-eosin-stained sections, (2) vascular permeability was measured by intravenous Evans blue injections, and (3) local CBF (lCBF) was quantified using the iodo-[14C]antipyrine technique. Dose-dependent increases were found in (1) vessel density and size (only vessels >43 microm could be quantified morphologically), (2) Evans blue extravasation and brain edema formation, and (3) lCBF (up to eightfold). At medium doses, hyperemic areas and smaller areas of decreased lCBF were found. In low flow areas, vascular cross-sectional areas were increased 223-fold and vessel density up to 10-fold. In high flow areas, these parameters were increased 32-fold and up to 15-fold, respectively. Adenovirus mediated VEGF overexpression results in (1) increased vessel size and density, (2) areas of increased and of decreased flow, and (3) more and smaller vessels in high flow than in low flow areas. These results indicate a diverging flow pattern of newly formed vessels.
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PMID:Heterologous expression of human VEGF165 in rat brain: dose-dependent, heterogeneous effects on CBF in relation to vascular density and cross-sectional area. 1267 19

Angiogenesis is the development of blood capillaries from pre-existing vessels. Vascular endothelial growth factor (VEGF) is a key regulator of vessel growth and regression, and acts as an endothelial survival factor by protecting endothelial cells from apoptosis. Many genes involved in cell proliferation and apoptosis are regulated by the nuclear factor kappa B (NFkappaB) transcription factor family. This study aimed to address the hypothesis that VEGF-mediated survival effects on endothelium involve NFkappaB. Using an NFkappaB-luciferase reporter adenovirus, we observed activation of NFkappaB following VEGF treatment of human umbilical vein endothelial cells. This was confirmed using electrophoretic mobility shift assay and found to involve nuclear translocation of NFkappaB sub-unit p65. However, NFkappaB activation occurred without degradation of inhibitory IkappaB proteins (IkappaBalpha, IkappaBbeta, and IkappaBepsilon). Instead, tyrosine phosphorylation of IkappaBalpha was observed following VEGF treatment, suggesting NFkappaB activation was mediated by degradation-independent dissociation of IkappaBalpha from NFkappaB. Adenovirus-mediated over-expression of either native IkappaBalpha, or of IkappaBalpha in which tyrosine residue 42 was mutated to phenylalanine, inhibited induction of NFkappaB-dependent luciferase activity in response to VEGF. Furthermore, VEGF-induced upregulation of mRNA for the anti-apoptotic protein Bcl-2 and cell survival following serum withdrawal was reduced following IkappaBalpha over-expression. This study highlights that different molecular mechanisms of NFkappaB activation may be involved downstream of stimuli which activate the endothelial lining of blood vessels.
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PMID:Vascular endothelial growth factor signalling in endothelial cell survival: a role for NFkappaB. 1641 78

Mesenchymal stem cells (MSCs) are suitable seed cells for bone tissue engineering because they can self-renew and undergo differentiation into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Vascular endothelial growth factor-a (VEGF-a), an angiogenic factor, is also involved in osteogenesis and bone repair. However, the effects of VEGF-a on osteogenic MSCs differentiation remain unknown. It was previously reported that bone morphogenetic protein9 (BMP9) is one of the most important osteogenic BMPs. Here, we investigated the effects of VEGF-a on BMP9-induced osteogenesis with mouse embryo fibroblasts (MEFs). We found that endogenous VEGF-a expression was undetectable in MSCs. Adenovirus-mediated expression of VEGF-a in MEFs potentiated BMP9-induced early and late osteogenic markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In stem cell implantation assays, VEGF-a augmented BMP9-induced ectopic bone formation. VEGF-a in combination with BMP9 effectively increased the bone volume and osteogenic activity. However, the synergistic effect was efficiently abolished by the phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002. These results demonstrated that BMP9 may crosstalk with VEGF-a through the PI3K/AKT signaling pathway to induce osteogenic differentiation in MEFs. Thus, our findings demonstrate the effects of VEGF-a on BMP9-induced bone formation and provide a new potential strategy for treating nonunion fractures, large segmental bony defects, and/or osteoporotic fractures.
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PMID:Adenovirus-mediated expression of vascular endothelial growth factor-a potentiates bone morphogenetic protein9-induced osteogenic differentiation and bone formation. 2700 41