Expression of angiogenic factors in juvenile rheumatoid arthritis: correlation with revascularization of human synovium engrafted into SCID mice.
OBJECTIVE
Although increased vascularity was noted in early histopathologic studies of juvenile rheumatoid arthritis (JRA) synovium, the available data on angiogenesis in JRA are very limited. The main purposes of this study were to assess expression of the key angiogenic factors in JRA synovium, and to evaluate a SCID mouse model of JRA as an approach to study in vivo regulation of the expression of these factors in JRA.


METHODS
RNase protection assay was used to assess the expression of the key angiogenic factors in fresh JRA synovium and in JRA synovial tissue fragments that had been minced and then implanted into SCID mice. Vascularity of the samples was assessed by immunohistochemical staining for von Willebrand factor. Synovial specimens obtained from patients with osteoarthritis (OA) or other noninflammatory arthropathies were used as controls.


RESULTS
Detectable levels of messenger RNA for vascular endothelial growth factor and angiopoietin 1 and their respective receptors, as well as endoglin and thrombin receptors, were present in all JRA tissue specimens studied. The levels of expression of these factors in JRA tissues were significantly higher than those in tissues obtained from patients with OA or other noninflammatory arthropathies. Furthermore, increased expression of the key angiogenic factors in the fresh JRA tissues correlated with the exuberant revascularization of JRA minced tissue fragments implanted into SCID mice. This was in sharp contrast to the poor revascularization of implanted OA tissues.


CONCLUSIONS
JRA synovium is characterized by high angiogenic activity. SCID mouse-human JRA synovium chimeras may provide a good approach to study the in vivo regulation of angiogenesis in JRA.
Scola
M P
MP
Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Imagawa
T
T
Boivin
G P
GP
Giannini
E H
EH
Glass
D N
DN
Hirsch
R
R
Grom
A A
AA
D042683:Angiopoietin-1; D000818:Animals; D015703:Antigens, CD; D001171:Arthritis, Juvenile / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D000071063:Endoglin; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology / Q000378:metabolism* / Q000637:transplantation; D016378:Tissue Transplantation; D014183:Transplantation, Heterologous; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D016228:Endothelial Growth Factors; D008222:Lymphokines; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors