The angiogenic pathway 'vascular endothelial growth factor/flk-I (KDR)-receptor' in rheumatoid arthritis and osteoarthritis

Active angiogenesis, together with an up-regulation of angiogenic factors, is evident in the synovium of both rheumatoid arthritis (RA) and osteoarthr itis (OA). The present study assessed, by immunohistochemistry, the microve ssel density in the synovium of these arthritides and in normal controls, i n relation to the expression of the angiogenic factors vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor ( PD-ECGF) and the apoptosis-related proteins bcl-2 and p53. More importantly , using the novel 11B5 MAb, the activated 'VEGF/flk-1(KDR)-receptor' microv essel density was assessed. VEGF expression in fibroblasts was diffuse in b oth RA and OA, Diffuse PD-ECGF expression of fibroblasts was noted in all c ases of RA, While fibroblast reactivity was focal in the OA material, The s tandard microvessel density (sMVD), as assessed with the anti-CD31 monoclon al antibody (MAb), was higher in RA (64 +/- 12) and in 0.4 (65 +/- 16) than in normal tissues (52+/-8; p = 0.008 and 0.0004, respectively). The activa ted microvessel density (aMVD), assessed with the 11B5 MAb, was significant ly higher in RA (29+/-10) than in OA (17+/-4; p<0.0001) and than in normal tissues (14+/-2; p<0.0001). The 'activation ratio' (aMVD/sMVD) was statisti cally higher in RA (0.46+/-0.17) than in OA and normal synovial tissues, th e latter two having a similar ratio (0.28+/-0.08 and 0.26+/-0.03, respectiv ely). Cytoplasmic bcl-2 expression was frequent in the synovial cells of 0. 4, but rare in RA, Nuclear p53 protein accumulation was never observed. It is suggested that the angiogenic pathway VEGF/flk-1(KDR) may play an import ant role in the pathogenesis of RA and OA, Thus, failure of VEGF/flk-1(KDR) activation, in the presence of increased VEGF expression, may indicate a s ynovium with an impaired capacity to establish a viable vasculature, consis tent with the degenerative nature of OA, On the other hand, the activated a ngiogenesis in RA shows a functional, still pathologically up-regulated VEG F/flk-1(KDR) pathway. Whether restoration of an impaired VEGF/flk-1(KDR) pa thway in OA, or inhibition of this in RA, would prove of therapeutic import ance requires further investigation, Copyright (C) 2001 John Wiley & Sons, Ltd.