Splice variants VEGF121 and VEGF165 of the angiogenic peptide vascular endothelial cell growth factor are expressed in the synovial tissue of patients with rheumatoid arthritis.
OBJECTIVE
To determine the expression of the angiogenic peptide vascular endothelial growth factor (VEGF, also known as vascular permeability factor, VPF) in the synovium of patients with rheumatoid arthritis (RA).


METHODS
Expression of VEGF protein from the synovial tissue of 10 patients with RA was monitored by ELISA and visualized by immunocytochemistry, and by double-staining with the VEGFR-1/flt-1. VEGF mRNA and its splice variants were determined by reverse transcriptase polymerase chain reaction (RT-PCR).


RESULTS
VEGF protein was strongly increased in rheumatoid synovium and localized at the synovial surface, whereas the VEGF receptor flt-1 (VEGFR-1) was visualized on microvessels in close vicinity. In synovial tissues from all 10 patients with RA, VEGF121 and VEGF165 were identified at the mRNA level as the only VEGF splice forms expressed.


CONCLUSIONS
Since VEGF165 and VEGF121 are differently diffusible due to their opposite heparan sulfate-binding properties, they act at different distances. The presence of VEGF121 may explain induction of the VEGFR-1 on infiltrating blood vessels near the synovial surface.
Pufe
T
T
Department of Anatomy, University of Kiel, Germany.
Petersen
W
W
Tillmann
B
B
Mentlein
R
R
D017398:Alternative Splicing; D001172:Arthritis, Rheumatoid / Q000503:physiopathology*; D016228:Endothelial Growth Factors / Q000235:genetics*; D015870:Gene Expression; D005910:Glioma; D006801:Humans; D008222:Lymphokines / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D013583:Synovial Membrane / Q000502:physiology*; D014407:Tumor Cells, Cultured; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1