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VEGF Activity (vegf + activity)
Selected AbstractsVascular regression is required for mesenchymal condensation and chondrogenesis in the developing limbDEVELOPMENTAL DYNAMICS, Issue 3 2001Melinda Yin Abstract Vascular regression occurs during limb mesenchymal cell condensation and chondrogenesis, but it is unclear whether it is required for these processes or is a secondary phenomenon without major regulatory roles. To address this issue, beads presoaked with the potent angiogenic factor vascular endothelial growth factor (VEGF) were implanted in the vicinity of the prospective digit 2 in early chick embryo wing buds and the effects on angiogenesis and digit development were determined over time. We found that VEGF treatment caused a marked local increase in blood vessel number and density. Strikingly, this was accompanied by inhibition of digit 2 development as revealed by lack of expression of chondrogenic transcription factor Sox9 and absence of Alcian blue staining. Vascular distribution and skeletal development in adjacent areas remained largely unaffected. Inhibition of digit formation and excess vascularization were both reversible upon further embryonic growth and dissipation of VEGF activity. When supernumerary digits were induced at the anterior limb margin by retinoic acid treatment, their development was also preceded by vascular regression; interestingly, cotreatment with VEGF inhibited supernumerary digit development as well. Direct exposure of limb mesenchymal cells in micromass cultures to VEGF caused no obvious effects on condensation and chondrogenesis, indicating that VEGF effects are not due to direct action on skeletal cells. Our results are the first to provide evidence that vascular regression is required for mesenchymal condensation and chondrogenesis. A model of how patterning mechanisms and vascular regression may intersect and orchestrate limb skeletogenesis is proposed. © 2001 Wiley-Liss, Inc. [source] Basic fibrobrast growth factor induces the secretion of vascular endothelial growth factor by human aortic smooth muscle cells but not by endothelial cellsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2003F. Belgore Abstract Background, Endothelial cell dysfunction and smooth muscle cell (SMC) proliferation are major events in atherogenesis. Both cells are a source of growth factors that mediate cellular proliferation and chemotaxis. Inappropriate production of, and/or response to, these growth factors (such as vascular endothelial growth factor, VEGF, and basic fibroblast growth factor (bFGF)) may contribute to atherogenesis and therefore to disease progression. Methods, Production of VEGF and its soluble receptor (sFlt-1) by human SMCs and human umbilical endothelial cells (HUVECs) after stimulation with bFGF were examined by ELISA of cell culture media and by Western blotting. Results, Smooth muscle cells produced significantly more VEGF than HUVECs (P < 0·05) after 24 h of culture with bFGF levels , 0·001 µg mL,1. bFGF induced dose-dependent production of VEGF by SMCs, where maximum production was present in 1 µg mL,1 of bFGF. Conversely, the SMCs produced less sFlt-1 than HUVECs (P < 0·05). However, bFGF induced dose-dependent phosphorylation of Flt1 and another VEGF receptor, KDR, in HUVECs but not SMCs. There was no VEGF or sFLT-1 after 6 h of culture in any dose of bFGF in either type of cell. Conclusions, Differences in the production of VEGF and sFlt-1 by SMCs and HUVECs are consistent with the role of these cells in angiogenesis. Induction of VEGF production and expression by bFGF in these cells indicates that this growth factor may participate in angiogenesis indirectly by the induction of VEGF. The production of sFlt-1 by both cell types is in agreement with the notion that sFlt-1 may be involved in the regulation of VEGF activity. Additionally, the ability of bFGF to induce dose-dependent phosphorylation of KDR in HUVECs highlights the important role of bFGF in VEGF-mediated angiogenic processes. [source] A VEGF Trap Inhibits the Beneficial Effect of bFGF on Vasoreactivity in Corporal Tissues of Hypercholesterolemic RabbitsTHE JOURNAL OF SEXUAL MEDICINE, Issue 9 2008Donghua Xie MD ABSTRACT Introduction., Hypercholesterolemia causes a decrease in normal corporal tissue vasoreactivity in a preclinical model of erectile dysfunction. Previous studies have shown that intracorporal injection (ICI) of basic fibroblast growth factor (bFGF) reverses some of the detrimental vasoreactivity effects of hypercholesterolemia and increases vascular endothelial growth factor (VEGF) expression. Aim., We sought to determine whether the beneficial effects of bFGF are VEGF-mediated. Methods., A total of 32 New Zealand white rabbits were fed a 1% cholesterol diet for 6 weeks and randomly divided into four groups (N = 8/group). Group 1 received a 2.5 µg bFGF ICI and 2.5 × 1011 viral particle unit (vpu) of adenovirus encoding ,-galactosidase (Ad,-gal) ICI, 10 days later. Group 2 received a 2.5 µg bFGF ICI and 2.5 × 1011 vpu of adenovirus encoding soluble VEGF receptor (VEGFR) (AdsVEGFR, a VEGF trap) ICI, 10 days later. Group 3 received phosphate buffered saline solution (PBS) ICI and 2.5 × 1011 vpu Ad,-gal ICI, 10 days later. Group 4 received PBS ICI and 2.5 × 1011 vpu AdsVEGFR ICI, 10 days later. Main Outcome Measures., The corpus cavernosum was harvested for vasoreactivity studies 10 days post viral injection. The effective dose of 50% maximum relaxation was determined. VEGF levels were assessed by enzyme-linked immunosorbent assay. Total and phoshorylated Akt and endothelial nitric oxide were analyzed by Western blot. Results., Endothelium-dependent vasoreactivity was significantly greater in Group 1 vs. all other groups. The VEGF trap eliminated the beneficial effects of bFGF on endothelium-dependent vasoreactivity and decreased Akt and nitric oxide phosphorylation. Conclusions., These data demonstrate that VEGF activity contributes much of the therapeutic modulation of bFGF-mediated vasoreactivity in corporal tissue. Xie D, Findley CM, Greenfield JM, Pippen AM, Kontos CD, Donatucci CF, and Annex BH. A VEGF trap inhibits the beneficial effect of bFGF on vasoreactivity in corporal tissues of hypercholesterolemic rabbits. J Sex Med 2008;5:2069,2078. [source] Angiogenesis in patients with craniopharyngiomasCANCER, Issue 3 2002Correlation with treatment, outcome Abstract BACKGROUND Craniopharyngiomas are histologically benign epithelial neoplasms of the sellar region that often exhibit aggressive and invasive growth. The authors hypothesized that tumor proliferation, spread, and recurrence are angiogenesis dependent and investigated the significance of vascularization relative to biologic behavior. To the authors' knowledge, angiogenesis for patients with craniopharyngiomas has not been examined to date. METHODS The authors measured microvessel densities in resected, histologically proven craniopharyngiomas using immunostains for CD-34, a monoclonal antibody that selectively recognizes endothelial cells. Both histologic types of craniopharyngiomas, adamantinomatous and papillary, were included in the study. In addition, the cellular distribution of vascular endothelial growth factor (VEGF), a strong stimulator of new vessel formation, was assessed by both immunohistochemistry and in situ hybridization for VEGF receptor 2 (VEGFR-2) mRNA expression. RESULTS Histologically, small numbers of capillaries were identified in temporal stroma but not in their epithelial components. Immunohistochemistry revealed strong, conclusive cytoplasmic immunoreactivity for VEGF in the epithelial cells of both adamantinomatous craniopharyngiomas and papillary craniopharyngiomas. In situ hybridization showed that VEGFR-2 mRNA was expressed widely, not only in neoplastic epithelium but also in capillary endothelium. CONCLUSIONS Tumors with greater microvessel density regrow more frequently compared with tumors that have lower microvessel density, suggesting that the extent of angiogenesis is of prognostic value in patients with craniopharyngioma. VEGFR-2 may act as a key modulator of VEGF activity in endothelial cells and nonendothelial cells, indicating that VEGF plays an important role in the behavior of craniopharyngiomas. Cancer 2002;94:738,45. © 2002 American Cancer Society. DOI 10.1002/cncr.10281 [source] | ||||||||||