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Titolo:
The angiogenic pathway 'vascular endothelial growth factor/flk-I (KDR)-receptor' in rheumatoid arthritis and osteoarthritis
Autore:
Giatromanolaki, A; Sivridis, E; Atanassou, N; Zois, E; Thorpe, PE; Brekken, RA; Gatter, KC; Harris, AL; Koukourakis, IM; Koukourakis, MI;
Indirizzi:
Democritus Univ Thrace, Dept Pathol, Alexandroupolis 68100, Greece Democritus Univ Thrace Alexandroupolis Greece 68100 upolis 68100, Greece Univ Oxford, Oxford Radcliffe Hosp, Nuffield Dept Pathol, Oxford OX3 7LJ, England Univ Oxford Oxford England OX3 7LJ Dept Pathol, Oxford OX3 7LJ, England Univ Oxford, Oxford Radcliffe Hosp, Imperial Canc Res Fund, Med Oncol Unit, Oxford OX3 7LJ, England Univ Oxford Oxford England OX3 7LJ d Oncol Unit, Oxford OX3 7LJ, England Venizel Gen Hosp, Dept Orthoped, Heraklion, Crete, Greece Venizel Gen Hosp Heraklion Crete Greece thoped, Heraklion, Crete, Greece Venizel Gen Hosp, Dept Pathol, Heraklion, Crete, Greece Venizel Gen Hosp Heraklion Crete Greece Pathol, Heraklion, Crete, Greece Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75235 USA Univ Texas Dallas TX USA 75235 Ctr, Dept Pharmacol, Dallas, TX 75235 USA Univ Thessalia, Dept Radiotherapy Oncol, Larissa, Greece Univ Thessalia Larissa Greece Dept Radiotherapy Oncol, Larissa, Greece
Titolo Testata:
JOURNAL OF PATHOLOGY
fascicolo: 1, volume: 194, anno: 2001,
pagine: 101 - 108
SICI:
0022-3417(200105)194:1<101:TAP'EG>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
THYMIDINE PHOSPHORYLASE EXPRESSION; NECROSIS-FACTOR-ALPHA; CELL LUNG-CANCER; SYNOVIAL FIBROBLASTS; TYROSINE KINASE; TISSUE-SECTIONS; OSTEO-ARTHRITIS; FACTOR-BETA; IFN-GAMMA; TGF-BETA;
Keywords:
VEGF; flk-1(KDR); PD-ECGF; angiogenesis; rheumatoid arthritis; osteoarthritis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
42
Recensione:
Indirizzi per estratti:
Indirizzo: Koukourakis, MI Tumour & Angiogenesis Res Grp, 18 Dimokratias Ave, Iraklion 71306, Crete, Greece Tumour & Angiogenesis Res Grp 18 Dimokratias Ave Iraklion Crete Greece 71306
Citazione:
A. Giatromanolaki et al., "The angiogenic pathway 'vascular endothelial growth factor/flk-I (KDR)-receptor' in rheumatoid arthritis and osteoarthritis", J PATHOLOGY, 194(1), 2001, pp. 101-108

Abstract

Active angiogenesis, together with an up-regulation of angiogenic factors,is evident in the synovium of both rheumatoid arthritis (RA) and osteoarthritis (OA). The present study assessed, by immunohistochemistry, the microvessel density in the synovium of these arthritides and in normal controls, in 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' microvessel density was assessed. VEGF expression in fibroblasts was diffuse in both RA and OA, Diffuse PD-ECGF expression of fibroblasts was noted in all cases of RA, While fibroblast reactivity was focal in the OA material, The standard microvessel density (sMVD), as assessed with the anti-CD31 monoclonal 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 activated microvessel density (aMVD), assessed with the 11B5 MAb, was significantly higher in RA (29+/-10) than in OA (17+/-4; p<0.0001) and than in normaltissues (14+/-2; p<0.0001). The 'activation ratio' (aMVD/sMVD) was statistically higher in RA (0.46+/-0.17) than in OA and normal synovial tissues, the latter two having a similar ratio (0.28+/-0.08 and 0.26+/-0.03, respectively). Cytoplasmic bcl-2 expression was frequent in the synovial cells of 0.4, but rare in RA, Nuclear p53 protein accumulation was never observed. Itis suggested that the angiogenic pathway VEGF/flk-1(KDR) may play an important 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 synovium with an impaired capacity to establish a viable vasculature, consistent with the degenerative nature of OA, On the other hand, the activated angiogenesis in RA shows a functional, still pathologically up-regulated VEGF/flk-1(KDR) pathway. Whether restoration of an impaired VEGF/flk-1(KDR) pathway in OA, or inhibition of this in RA, would prove of therapeutic importance requires further investigation, Copyright (C) 2001 John Wiley & Sons,Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 08:27:06