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Angiopoietins, Growth Factors, and Vascular Morphology in Early Arthritis
URSULA FEARON, KONSTANTINA GRIOSIOS, ALEXANDER FRASER, RICHARD REECE, PAUL EMERY, PAMELA F. JONES, and DOUGLAS J. VEALE
ABSTRACT. 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-ß (TGF-ß1), and tumor necrosis factor-a (TNF-a) 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-ß1 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-a concentrations were similar in both groups. Conclusion. This is the first report of angiopoietin expression in early inflammatory arthritis. There is a close relationship between angiopoietins, VEGF, TGF-ß, and vascular morphology. There is differential angiogenesis at an early stage of inflammation, with major pathogenic and therapeutic implications. (J Rheumatol 2003;30:260-8) Key Indexing Terms:
ANGIOPOIETINS
From the Rheumatology Rehabilitation Research Unit and the Molecular Medicine Unit, University of Leeds, Leeds, UK. Supported by the Arthritis Research Campaign, Yorkshire Cancer Research, British Heart Foundation, and the Medical Research Council. U. Fearon, PhD, Research Scientist; A. Fraser, MB, MRCPI, Research Fellow; R. Reece, MBBCH, MRCPI, Consultant Rheumatologist; P. Emery, MA, MD, FRCP, ARC Professor of Rheumatology; D.J. Veale, MD, FRCPI, FRCP, Senior Lecturer in Rheumatology, Rheumatology Rehabilitation Research Unit; K. Griosios, PhD, Research Scientist; P.F. Jones, DPhil, Senior Research Scientist, Molecular Medicine Unit. Address reprint requests to Dr. U. Fearon, Department of Rheumatology, St. Vincent's Hospital, Elm Park, Dublin 4, Ireland. Submitted November 9, 2001; revision accepted July 12, 2002. |