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Endothelial Cell Responses (endothelial + cell_response)
Selected AbstractsEndothelial Cell Responses To Hypoxic StressCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2000Article first published online: 24 DEC 200 No abstract is available for this article. [source] Fibrinogen binding potentiates FGF-2 but not VEGF induced expression of u-PA, u-PAR, and PAI-1 in endothelial cellsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 9 2004A. Sahni Summary., ,Endothelial cell responses at sites of injury occur in a fibrin matrix and are regulated by growth factors including those of the FGF and VEGF families. The pericellular proteolytic balance is important in these responses, and FGF-2 and VEGF up-regulate endothelial cell u-PA, u-PAR and PAI-1. Because both VEGF and FGF-2 bind to fibrinogen, we have examined the capacity of fibrinogen to modulate the up-regulation of these proteins by FGF-2 and VEGF. Confluent cultures of endothelial cells were exposed to FGF-2, VEGF, and fibrinogen or to combinations of growth factors with fibrinogen. Changes in mRNA levels of u-PA, u-PAR and PAI-1 were measured by Northern blot. FGF-2 increased u-PA, u-PAR, and PAI-1 mRNA, but there was a significantly greater induction when fibrinogen was added to FGF-2 at all concentrations. The potentiation by fibrinogen was particularly evident at an FGF-2 concentration of 0.1 ng mL,1, which resulted in non-significant change in transcript levels by itself, but significantly increased up to 2.6-fold with fibrinogen. VEGF also increased endothelial cell expression of u-PA, u-PAR and PAI-1, but this effect was not potentiated by fibrinogen. Addition of LM609, a monoclonal antibody to ,V,3, significantly inhibited induction of u-PA mRNA and activity by fibrinogen,bound FGF-2 compared to FGF-2. A monoclonal antibody to FGFR1 also inhibited u-PA mRNA expression induced by fibrinogen-bound FGF-2. We conclude that fibrinogen increases the capacity of FGF-2, but not of VEGF, to up-regulate u-PA, u-PAR, and PAI-1 in endothelial cells and that fibrinogen-bound FGF-2 requires ,V,3 binding to up-regulate endothelial cell u-PA. [source] Age-dependent vascular endothelial growth factor expression and angiogenic capability of bladder smooth muscle cells: implications for cell-seeded technology in bladder tissue engineeringJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 8 2009Joseph Azzarello Abstract Cell seeding technology is commonly used in the field of tissue engineering to enhance the performance of bioscaffolds and promote tissue regeneration. The age of cells used for ex vivo seeding to achieve maximal tissue regeneration has not been defined. Since rapid angiogenesis is the most critical step for tissue graft survival and success, we evaluated passage-dependent vascular endothelial growth factor (VEGF) expression in cultured smooth muscle cells (SMCs) obtained from urinary bladder and endothelial cell response to bladder SMCs. Levels of various VEGF isoforms mRNA expression and total VEGF secretion were determined by a semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) and an enzyme-linked immunosorbent assay (ELISA) analysis, respectively. In vitro endothelial cell migration in Transwell® and capillary-like tube formation in MatrigelÔ were used to predict the ability of bladder SMCs to promote angiogenesis. VEGF produced by cultured bladder SMCs increased from passages 4 to 7, and decreased from passages 7 to 12 at both mRNA and protein levels. Endothelial cell migration as well as capillary-like tube formation correlated with levels of VEGF expression by bladder SMCs. Pre-incubation of endothelial cells with a VEGF receptor 1/2 inhibitor, SU5416, significantly reduced the number of capillary-like tubes in SMC-endothelial cell MatrigelÔ co-culture, and confirmed the involvement of VEGF in endothelial cell tube formation. Our results demonstrate that cell passage number is related to levels of VEGF production, which may translate to angiogenesis in engineered tissues. Copyright © 2009 John Wiley & Sons, Ltd. [source] Pyrazolo,pyrimidine-derived c-Src inhibitor reduces angiogenesis and survival of squamous carcinoma cells by suppressing vascular endothelial growth factor production and signalingINTERNATIONAL JOURNAL OF CANCER, Issue 5 2007Sandra Donnini Abstract Src tyrosine kinase family cooperates with activated growth factor receptors to regulate growth, invasion and metastasis. The authors examined the influence of a novel c-Src inhibitor, 1l, derived from 4-amino-substituted-pyrazolo,pyrimidines, on tumor angiogenesis and on the angiogenic output of squamous carcinoma cells, A431 and SCC-4. The effect of 1l was assessed on growth and microvessel density in A431 tumors and its effect compared with the established c-Src inhibitor PP-1. The effects of c-Src inhibition were investigated on vascular endothelial growth factor (VEGF) expression and activity in tumor cells grown in vivo and in vitro, as well as on VEGF mediated signaling and on endothelial cell functions. Nanomolar concentrations of 1l decreased tumor volume promoted by A431 implanted in nude mice, without affecting in vitro cell tumor survival. This effect was related to 1l inhibition of VEGF production, and secondary to an effect on tumor microvessel density. The rabbit cornea assay confirmed that 1l markedly decreased neovessel growth induced by VEGF. In cultured endothelial cells, 1l inhibited the VEGF-induced phosphorylation on tyr416 of c-Src, resulting in a reduced cell proliferation and invasion. Consistently, 1l dowregulated endothelial nitric oxide synthase, MAPK-extracellular receptor kinase 1,2 (ERK1-2) activity and matrix metalloproteinases (MMP-2/MMP-9), while the tissue inhibitors of metalloproteinases (TIMP2/TIMP-1) were upregulated. These results demonstrate that nM concentrations of c-Src kinase inhibitors (1l and PP-1), by reducing the production of VEGF released by tumor cell and its endothelial cell responses, have a highly selective antiangiogenesis effect, which might be useful in combination therapies. © 2006 Wiley-Liss, Inc. [source] | ||||||||||