Vascular permeability factor/endothelial growth factor (VPF/VEGF)

Accumulation and expression in human synovial fluids and rheumatoid synovial tissue

Roy A. Fava, Nancy Olsen, George Spencer-Green, Kiang Teck Yeo, Tet Kin Yeo, Brygida Berse, Robert W. Jackman, Donald R. Senger, Harold F. Dvorak, Lawrence F. Brown

Research output: Contribution to journalArticle

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Abstract

Vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), is a potent microvascular permeability enhancing cytokine and a selective mitogen for endothelial cells. It has been implicated in tumor angiogenesis and ascites fluid accumulation. Since development of the destructive synovial pannus in rheumatoid arthritis (RA) is associated with changes in vascular permeability (synovial fluid accumulation), synovial cell hyperplasia, and angiogenesis, we examined synovial fluids (SFs) and joint tissue for the expression and local accumulation of VPF/VEGF. VPF/VEGF was detected in all of 21 synovial fluids examined and when measured by an immunofluorimetric assay, ranged from 6.9 to 180.5 pM. These levels are biologically significant, since <1 pM VPF/VEGF can elicit responses from its target cells, endothelial cells. Levels of VPF/VEGF were highest in rheumatoid arthritis fluids (n = 10), with a mean value (± SEM) of 59.1 ± 18.0 pM, vs. 21.4 ± 2.3 pM for 11 SFs from patients with other forms of arthritis (p = 0.042). In situ hybridization studies that were performed on joint tissues from patients with active RA revealed that synovial lining macrophages strongly expressed VPF/VEGF mRNA, and that microvascular endothelial cells of nearby blood vessels strongly expressed mRNA for the VPF/VEGF receptors, fit-1 and KDR. Immunohistochemistry performed on inflamed rheumatoid synovial tissue revealed that the VPF/VEGF peptide was localized to macrophages within inflamed synovium, as well as to microvascular endothelium, its putative target in the tissue. Together, these findings indicate that VPF/VEGF may have an important role in the pathogenesis of RA.

Original languageEnglish (US)
Pages (from-to)341-346
Number of pages6
JournalJournal of Experimental Medicine
Volume180
Issue number1
DOIs
StatePublished - Jul 1 1994

Fingerprint

Endothelial Growth Factors
Synovial Fluid
Vascular Endothelial Growth Factor A
Rheumatoid Arthritis
Vascular Endothelial Growth Factor Receptor
Endothelial Cells
Capillary Permeability
Joints
Macrophages
Messenger RNA
Synovial Membrane
Mitogens
Ascites
Arthritis
Endothelium
Hyperplasia
In Situ Hybridization
Blood Vessels
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Fava, Roy A. ; Olsen, Nancy ; Spencer-Green, George ; Yeo, Kiang Teck ; Yeo, Tet Kin ; Berse, Brygida ; Jackman, Robert W. ; Senger, Donald R. ; Dvorak, Harold F. ; Brown, Lawrence F. / Vascular permeability factor/endothelial growth factor (VPF/VEGF) : Accumulation and expression in human synovial fluids and rheumatoid synovial tissue. In: Journal of Experimental Medicine. 1994 ; Vol. 180, No. 1. pp. 341-346.
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abstract = "Vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), is a potent microvascular permeability enhancing cytokine and a selective mitogen for endothelial cells. It has been implicated in tumor angiogenesis and ascites fluid accumulation. Since development of the destructive synovial pannus in rheumatoid arthritis (RA) is associated with changes in vascular permeability (synovial fluid accumulation), synovial cell hyperplasia, and angiogenesis, we examined synovial fluids (SFs) and joint tissue for the expression and local accumulation of VPF/VEGF. VPF/VEGF was detected in all of 21 synovial fluids examined and when measured by an immunofluorimetric assay, ranged from 6.9 to 180.5 pM. These levels are biologically significant, since <1 pM VPF/VEGF can elicit responses from its target cells, endothelial cells. Levels of VPF/VEGF were highest in rheumatoid arthritis fluids (n = 10), with a mean value (± SEM) of 59.1 ± 18.0 pM, vs. 21.4 ± 2.3 pM for 11 SFs from patients with other forms of arthritis (p = 0.042). In situ hybridization studies that were performed on joint tissues from patients with active RA revealed that synovial lining macrophages strongly expressed VPF/VEGF mRNA, and that microvascular endothelial cells of nearby blood vessels strongly expressed mRNA for the VPF/VEGF receptors, fit-1 and KDR. Immunohistochemistry performed on inflamed rheumatoid synovial tissue revealed that the VPF/VEGF peptide was localized to macrophages within inflamed synovium, as well as to microvascular endothelium, its putative target in the tissue. Together, these findings indicate that VPF/VEGF may have an important role in the pathogenesis of RA.",
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Vascular permeability factor/endothelial growth factor (VPF/VEGF) : Accumulation and expression in human synovial fluids and rheumatoid synovial tissue. / Fava, Roy A.; Olsen, Nancy; Spencer-Green, George; Yeo, Kiang Teck; Yeo, Tet Kin; Berse, Brygida; Jackman, Robert W.; Senger, Donald R.; Dvorak, Harold F.; Brown, Lawrence F.

In: Journal of Experimental Medicine, Vol. 180, No. 1, 01.07.1994, p. 341-346.

Research output: Contribution to journalArticle

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T1 - Vascular permeability factor/endothelial growth factor (VPF/VEGF)

T2 - Accumulation and expression in human synovial fluids and rheumatoid synovial tissue

AU - Fava, Roy A.

AU - Olsen, Nancy

AU - Spencer-Green, George

AU - Yeo, Kiang Teck

AU - Yeo, Tet Kin

AU - Berse, Brygida

AU - Jackman, Robert W.

AU - Senger, Donald R.

AU - Dvorak, Harold F.

AU - Brown, Lawrence F.

PY - 1994/7/1

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N2 - Vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), is a potent microvascular permeability enhancing cytokine and a selective mitogen for endothelial cells. It has been implicated in tumor angiogenesis and ascites fluid accumulation. Since development of the destructive synovial pannus in rheumatoid arthritis (RA) is associated with changes in vascular permeability (synovial fluid accumulation), synovial cell hyperplasia, and angiogenesis, we examined synovial fluids (SFs) and joint tissue for the expression and local accumulation of VPF/VEGF. VPF/VEGF was detected in all of 21 synovial fluids examined and when measured by an immunofluorimetric assay, ranged from 6.9 to 180.5 pM. These levels are biologically significant, since <1 pM VPF/VEGF can elicit responses from its target cells, endothelial cells. Levels of VPF/VEGF were highest in rheumatoid arthritis fluids (n = 10), with a mean value (± SEM) of 59.1 ± 18.0 pM, vs. 21.4 ± 2.3 pM for 11 SFs from patients with other forms of arthritis (p = 0.042). In situ hybridization studies that were performed on joint tissues from patients with active RA revealed that synovial lining macrophages strongly expressed VPF/VEGF mRNA, and that microvascular endothelial cells of nearby blood vessels strongly expressed mRNA for the VPF/VEGF receptors, fit-1 and KDR. Immunohistochemistry performed on inflamed rheumatoid synovial tissue revealed that the VPF/VEGF peptide was localized to macrophages within inflamed synovium, as well as to microvascular endothelium, its putative target in the tissue. Together, these findings indicate that VPF/VEGF may have an important role in the pathogenesis of RA.

AB - Vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), is a potent microvascular permeability enhancing cytokine and a selective mitogen for endothelial cells. It has been implicated in tumor angiogenesis and ascites fluid accumulation. Since development of the destructive synovial pannus in rheumatoid arthritis (RA) is associated with changes in vascular permeability (synovial fluid accumulation), synovial cell hyperplasia, and angiogenesis, we examined synovial fluids (SFs) and joint tissue for the expression and local accumulation of VPF/VEGF. VPF/VEGF was detected in all of 21 synovial fluids examined and when measured by an immunofluorimetric assay, ranged from 6.9 to 180.5 pM. These levels are biologically significant, since <1 pM VPF/VEGF can elicit responses from its target cells, endothelial cells. Levels of VPF/VEGF were highest in rheumatoid arthritis fluids (n = 10), with a mean value (± SEM) of 59.1 ± 18.0 pM, vs. 21.4 ± 2.3 pM for 11 SFs from patients with other forms of arthritis (p = 0.042). In situ hybridization studies that were performed on joint tissues from patients with active RA revealed that synovial lining macrophages strongly expressed VPF/VEGF mRNA, and that microvascular endothelial cells of nearby blood vessels strongly expressed mRNA for the VPF/VEGF receptors, fit-1 and KDR. Immunohistochemistry performed on inflamed rheumatoid synovial tissue revealed that the VPF/VEGF peptide was localized to macrophages within inflamed synovium, as well as to microvascular endothelium, its putative target in the tissue. Together, these findings indicate that VPF/VEGF may have an important role in the pathogenesis of RA.

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