Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide.

Tuder, Rubin M.; Flook, B E; Voelkel, Norbert F.

doi:10.1172/jci117858

Cited by 541 publications

(376 citation statements)

References 30 publications

(29 reference statements)

Supporting

Mentioning

330

Contrasting

Unclassified

Order By: Relevance

“…Expression of VEGF is known to be regulated by other mediators, including platelet-derived growth factor (35), TGF-␤ (36), IL-1 (28), oxygen radicals and nitric oxide (30,(37)(38)(39), and hypoxia (32,38,40). The synovium is chronically hypoxic in RA and probably also in CIA: biochemical evidence of anaerobic metabolism suggests that blood flow is insufficient to meet the high metabolic demands of inflamed synovial tissue (41).…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor Expression and Regulation of Murine Collagen-Induced Arthritis

Kasama

Kobayashi

et al. 2000

The Journal of Immunology

130

View full text Add to dashboard Cite

We have examined the expression and function of the angiogenic factor, vascular endothelial growth factor (VEGF) during the evolution of type II collagen-induced arthritis (CIA). Biologically active VEGF was expressed along a time course that paralleled the expression of two specific VEGF receptors, Flk-1 and Flt-1, and the progression of joint disease. Moreover, levels of VEGF expression correlated with the degree of neovascularization, as defined by vWF levels, and arthritis severity. Macrophage- and fibroblast-like cells, which infiltrated inflamed sites and were then activated by other inflammatory mediators, are probably important sources of VEGF and may thus regulate angiogenesis during the development of CIA. Administration of anti-VEGF antiserum to CIA mice before the onset of arthritis delayed the onset, reduced the severity, and diminished the vWF content of arthritic joints. By contrast, administration of anti-VEGF antiserum after the onset of the disease had no effect on the progression or ultimate severity of the arthritis. These data suggest that VEGF plays a crucial role during an early stage of arthritis development, affecting both neovascularization and the progression of experimentally induced synovitis.

show abstract

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Growth Factor Expression and Regulation of Murine Collagen-Induced Arthritis

Kasama

Kobayashi

et al. 2000

The Journal of Immunology

130

View full text Add to dashboard Cite

show abstract

“…In light of the fact that both TNF and VEGF can induce angiogenesis in vivo [29,30], a possible involvement of the here described synergistic tissue factor induction in angiogenic processes may be considered, especially when low concentrations of TNF and high concentrations of VEGF are present. Candidate pathological situations, when VEGF and its receptors are up-regulated, had been described for tumors [31,32], rheumatoid arthritis [33,34] and hypoxic lungs [35], but coexpression of TNF has not been studied in all of these examples. Further experimental in vivo data are required to test the hypothesis that TNF/VEGF-mediated tissue factor production is also involved in angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Synergistic induction of endothelial tissue factor by tumor necrosis factor and vascular endothelial growth factor: functional analysis of the tumor necrosis factor receptors

et al. 1996

View full text Add to dashboard Cite

Tissue factor expression on the surface of endothefial cells can be induced by tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF) in a synergistic manner. We have investigated the role of the two different TNF receptors for this synergy. Firstly, stimulation of the 60 kDa TNF receptor (TNFR60) by a mutant of TNF specific for TNFR60 induced responses comparable to wild-type TNF. In contrast, stimulation of TNFR80 by a TNFR80-specific TNF mutein did not result in enhancement of tissue factor expression even in the presence of a suboptimal TNFR60 triggering. Secondly, we tested neutralizing TNF receptor antibodies for inhibition of tissue factor synthesis induced by VEGF and TNF. A TNFR60-specific antibody inhibited tissue factor production over a broad range of TNF concentrations, indicating an essential role of TNFR60 in the TNF/VEGF synergy. In contrast, blocking of TNF binding to TNFR80 strongly inhibited TNF-induced tissue factor expression at low, but less pronounced at high, TNF concentrations. In conclusion, these data are in agreement with a model in which TNFR80 participates in the synergy between VEGF and low concentrations of soluble TNF by passing the ligand to the signalling TNFR60.

show abstract

“…Exposure to hypoxia rapidly induces VEGF-A expression (27)(28)(29). Hypoxia-induced transcription of VEGF is mediated by hypoxia-inducible factor-1, an element in the VEGF-A gene promotor (26,(30)(31)(32)99).…”

Section: Vascular Endothelial Growth Factor (Vegf) Ligands: Structurementioning

confidence: 99%

VEGF Receptor Signaling and Endothelial Function

Kliche¹,

2001

View full text Add to dashboard Cite

show abstract

Increased gene expression for VEGF and the VEGF receptors KDR/Flk and Flt in lungs exposed to acute or to chronic hypoxia. Modulation of gene expression by nitric oxide.

Cited by 541 publications

References 30 publications

Vascular Endothelial Growth Factor Expression and Regulation of Murine Collagen-Induced Arthritis

Vascular Endothelial Growth Factor Expression and Regulation of Murine Collagen-Induced Arthritis

Synergistic induction of endothelial tissue factor by tumor necrosis factor and vascular endothelial growth factor: functional analysis of the tumor necrosis factor receptors

VEGF Receptor Signaling and Endothelial Function

Contact Info

Product

Resources

About