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VEGF Family (vegf + family)
Selected AbstractsFibrinogen 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] The C-terminus of viral vascular endothelial growth factor-E partially blocks binding to VEGF receptor-1FEBS JOURNAL, Issue 1 2008Marie K. Inder Vascular endothelial growth factor (VEGF) family members play important roles in embryonic development and angiogenesis during wound healing and in pathological conditions such as tumor formation. Parapoxviruses express a new member of the VEGF family which is a functional mitogen that specifically activates VEGF receptor (VEGFR)-2 but not VEGFR-1. In this study, we show that deletion from the viral VEGF of a unique C-terminal region increases both VEGFR-1 binding and VEGFR-1-mediated monocyte migration. Enzymatic removal of O -linked glycosylation from the C-terminus also increased VEGFR-1 binding and migration of THP-1 monocytes indicating that both the C-terminal residues and O -linked sugars contribute to blocking viral VEGF binding to VEGFR-1. The data suggest that conservation of the C-terminal residues throughout the viral VEGF subfamily may represent a means of reducing the immunostimulatory activities associated with VEGFR-1 activation while maintaining the ability to induce angiogenesis via VEGFR-2. [source] Systems Biology of Vascular Endothelial Growth FactorsMICROCIRCULATION, Issue 8 2008FEILIM MAC GABHANN ABSTRACT Several cytokine families have roles in the development, maintenance, and remodeling of the microcirculation. Of these, the vascular endothelial growth factor (VEGF) family is one of the best studied and one of the most complex. Five VEGF ligand genes and five cell-surface receptor genes are known in the human, and each of these may be transcribed as multiple splice isoforms to generate an extensive family of proteins, many of which are subject to further proteolytic processing. Using the VEGF family as an example, we describe the current knowledge of growth-factor expression, processing, and transport in vivo. Experimental studies and computational simulations are being used to measure and predict the activity of these molecules, and we describe avenues of research that seek to fill the remaining gaps in our understanding of VEGF family behavior. [source] ID2-VEGF-related Pathways in the Pathogenesis of Kaposi's Sarcoma: A Link Disrupted by RapamycinAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009G. Stallone The Id-proteins are a family of four related proteins implicated in the control of differentiation and cell-cycle progression. Down-regulation of Id-gene expression is essential for the differentiation of several cell types. In addition, deregulated Id2 activity inhibits the Rb tumor suppressor pathway and promotes the expression of vascular endothelial growth factor (VEGF). Several members of VEGF family could be involved in Kaposi's sarcoma (KS) development and progression. Lymphatic vascular endothelial hyaluronan receptor-1 (LYVE-1) is the first marker of lymphatic endothelial competence during development in the mature vasculature, and is also expressed on KS spindle cells. Rapamycin (RAPA), an immunosuppressive drug, has been shown to reverse KS growth and to reduce tumor angiogenesis. We evaluate, in transplantation-associated KS and in cultured KS-cells the RAPA effect on Id2 and on de novo lymphangiogenesis. Markers of lymphatic-endothelial-cells (VEGFR-3, LYVE-1) and Id2, expressed at low levels within the normal skin, were up-regulated in KS and returned to normal levels after RAPA introduction. The association between Id2 and lymphangiogenesis is suggested by co-localization of Id2, VEGFR-3 and LYVE-1. RAPA inhibition on Id2 expression was confirmed in vitro in KS-cells, both in basal conditions and upon stimulation with VEGF. In conclusion, our data would suggest a novel molecular mechanism for the antineoplastic effects of RAPA in posttransplant KS. [source] Angiogenesis: now and then,APMIS, Issue 7-8 2004CARLA COSTA Angiogenesis or new blood vessel formation plays an essential role during embryogenesis, adult vascular remodeling and in several pathological disorders, as in tumor development. Although sprouting of blood vessels is the principal angiogenic mechanism, additional ones, such as the recruitment of bone marrow-derived cells, have recently been described. These processes are controlled by several molecules, although members of the VEGF family of angiogenic factors and its receptors seem to be the main mediators. Initially, VEGF receptors were described as endothelial specific; however, further studies have reported their presence in several types of cells of non-endothelial origin, such as tumor cells. This VEGF receptor altered expression has suggested an angiogenesis-independent growth advantage mechanism on certain types of cancers by the generation of autocrine loops. A possible role in tumorigenesis and a potential novel target in cancer therapy have been hypothesized. Detection of other receptors and molecules considered to be angiogenic players has also been observed on tumor cells. Currently, their clinical significance as well as their potential as therapeutic targets for the treatment of certain cancers is being evaluated, having in mind the future development of promising mechanism-based therapies. The aspects mentioned above are the main focus of this review, which aims to throw light on recent findings respecting angiogenesis and novel therapeutic approaches. [source] | ||||||||||