Angiopoietins, growth factors, and vascular morphology in early arthritis.
OBJECTIVE
To examine angiogenic growth factors in patients with early, untreated inflammatory arthritides and controls.


METHODS
Synovial membrane (SM) infiltrate and Ang1, Ang2, and vascular endothelial growth factor (VEGF) mRNA and protein expression were examined using immunohistochemistry and in situ hybridization. Synovial fluid (SF) VEGF, transforming growth factor-beta (TGF-beta 1), and tumor necrosis factor-alpha (TNF-alpha) protein were measured by ELISA. Vascular morphology was assessed at arthroscopy.


RESULTS
Ang2 mRNA and protein expression was observed in early psoriatic arthritis (PsA) and rheumatoid arthritis (RA) SM. Expression of Ang2 and VEGF was significantly greater in early PsA SM and correlated strongly. SF VEGF and TGF-beta 1 concentrations were also significantly higher in early PsA compared to RA. Distinct vascular morphology, with tortuous vessels in PsA, correlated with microscopic vascular scores (r = 0.54, p = 0.005) and VEGF levels (r = 0.51, p = 0.01). Ang1 mRNA and protein expression was observed, but concentrations were markedly lower than for Ang2 and VEGF. Clinical disease activity, SM infiltration, and SF TNF-alpha concentrations were similar in both groups.


CONCLUSIONS
This is the first report of angiopoietin expression in early inflammatory arthritis. There is a close relationship between angiopoietins, VEGF, TGF-beta, and vascular morphology. There is differential angiogenesis at an early stage of inflammation, with major pathogenic and therapeutic implications.
Fearon
Ursula
U
Rheumatology Rehabilitation Research Unit and the Molecular Medicine Unit, University of Leeds, Leeds, UK.
Griosios
Konstantina
K
Fraser
Alexander
A
Reece
Richard
R
Emery
Paul
P
Jones
Pamela F
PF
Veale
Douglas J
DJ
D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000032:analysis / Q000235:genetics*; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015535:Arthritis, Psoriatic / Q000473:pathology / Q000503:physiopathology; D001172:Arthritis, Rheumatoid / Q000473:pathology* / Q000503:physiopathology*; D001182:Arthroscopy; D016228:Endothelial Growth Factors / Q000032:analysis / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis / Q000235:genetics*; D008222:Lymphokines / Q000032:analysis / Q000235:genetics*; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics*; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D013583:Synovial Membrane / Q000098:blood supply / Q000737:chemistry / Q000473:pathology; D013585:Synovitis / Q000473:pathology / Q000503:physiopathology; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors