Fearon Ursula, Griosios Konstantina, Fraser Alexander, Reece Richard, Emery Paul, Jones Pamela F, Veale Douglas J
Rheumatology Rehabilitation Research Unit and the Molecular Medicine Unit, University of Leeds, Leeds, UK.
J Rheumatol. 2003 Feb;30(2):260-8.
To examine angiogenic growth factors in patients with early, untreated inflammatory arthritides and controls.
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.
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.
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.
检测早期未经治疗的炎性关节炎患者及对照组中的血管生成生长因子。
采用免疫组织化学和原位杂交技术检测滑膜（SM）浸润情况以及血管生成素1（Ang1）、血管生成素2（Ang2）和血管内皮生长因子（VEGF）的mRNA及蛋白表达。通过酶联免疫吸附测定（ELISA）法检测滑液（SF）中的VEGF、转化生长因子-β1（TGF-β1）和肿瘤坏死因子-α（TNF-α）蛋白。在关节镜检查时评估血管形态。
在早期银屑病关节炎（PsA）和类风湿关节炎（RA）的滑膜中观察到Ang2 mRNA和蛋白表达。早期PsA滑膜中Ang2和VEGF的表达显著更高且呈强相关性。与RA相比，早期PsA患者滑液中的VEGF和TGF-β1浓度也显著更高。PsA中血管形态各异，血管迂曲，这与微观血管评分（r = 0.54，p = 0.005）和VEGF水平（r = 0.51，p = 0.01）相关。观察到了Ang1 mRNA和蛋白表达，但浓度明显低于Ang2和VEGF。两组的临床疾病活动度、滑膜浸润情况及滑液TNF-α浓度相似。
这是关于血管生成素在早期炎性关节炎中表达的首次报道。血管生成素、VEGF、TGF-β与血管形态之间存在密切关系。在炎症早期存在不同的血管生成情况，具有重要的致病和治疗意义。
