Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arthritis, Experimental / etiology
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Arthritis, Experimental / immunology*
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Arthritis, Experimental / metabolism*
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Arthritis, Experimental / physiopathology
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Cells, Cultured
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Collagen / immunology*
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Endothelial Growth Factors / biosynthesis*
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Endothelial Growth Factors / genetics
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Endothelial Growth Factors / immunology
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Endothelial Growth Factors / metabolism
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Endothelium, Vascular
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Humans
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Immune Sera / administration & dosage
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Immunization, Passive
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Immunohistochemistry
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Lymphokines / biosynthesis*
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Lymphokines / genetics
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Lymphokines / immunology
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Lymphokines / metabolism
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Male
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Mice
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Mice, Inbred DBA
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Neovascularization, Physiologic / immunology
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Proto-Oncogene Proteins / genetics
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Receptor Protein-Tyrosine Kinases / genetics
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Receptors, Growth Factor / genetics
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Receptors, Vascular Endothelial Growth Factor
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Transcription, Genetic / immunology
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Umbilical Veins
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factor Receptor-1
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Vascular Endothelial Growth Factors
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von Willebrand Factor / metabolism
Substances
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Endothelial Growth Factors
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Immune Sera
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Lymphokines
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Proto-Oncogene Proteins
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Receptors, Growth Factor
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Vascular Endothelial Growth Factor A
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Vascular Endothelial Growth Factors
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von Willebrand Factor
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Collagen
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Receptor Protein-Tyrosine Kinases
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Receptors, Vascular Endothelial Growth Factor
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Vascular Endothelial Growth Factor Receptor-1