Department of Rheumatology and Clinical Immunology, University Medical Centre Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Clin Exp Rheumatol. 2009 Nov-Dec;27(6):945-51.
Despite the important role of the transcription factor HIF-1alpha in angiogenesis and inflammation, only a few studies on HIF-1alpha expression have been performed in RA patients. The aim of the present study was to identify the layer in synovial tissue of RA patients where HIF1a is expressed and to find out whether HIF-1alpha expression is related to both angiogenesis and inflammation in synovium from RA patients.
A reproducible staining method for HIF-1alpha was developed. HIF-1alpha -positive cells were quantified in synovial tissue from patients with RA. As control we used synovial tissue from patients with osteoarthritis (OA). The number of HIF-1alpha-positive cells was compared with the number of blood vessels present and was correlated with the amount of inflammation. The amount of inflammation was determined by counting inflammatory cells, by estimating the proliferation marker Ki67 in inflamed tissue, and by using a recently published synovitis score which gives an accurate estimate of the amount of inflammation present.
HIF-1alpha was expressed weakly in the lining layer and strongly in the sublining layer in RA synovial tissue. In contrast, HIF-1alpha was only weakly expressed in OA synovial tissue. The number of HIF-1alpha -positive cells correlated strongly with the number of blood vessels in RA synovial tissue and with inflammatory endothelial cell infiltration (blood vessels), cell proliferation (Ki67) and the synovitis score.
HIF-1alpha expression is strongest in the sub-lining layer of RA synovium and is related to both angiogenesis and inflammation in synovium from RA patients. These results thus suggest that HIF-1alpha could serve as an important new therapeutic target in RA, targeting both angiogenesis and inflammation.
尽管转录因子 HIF-1alpha 在血管生成和炎症中起着重要作用，但只有少数研究探讨了 RA 患者的 HIF-1alpha 表达。本研究旨在确定 RA 患者滑膜组织中 HIF1a 的表达部位，并探讨 HIF-1alpha 表达与 RA 患者滑膜中的血管生成和炎症是否相关。
开发了一种可重复的 HIF-1alpha 染色方法。对 RA 患者滑膜组织中的 HIF-1alpha 阳性细胞进行定量。以骨关节炎 (OA) 患者的滑膜组织作为对照。将 HIF-1alpha 阳性细胞的数量与存在的血管数量进行比较，并与炎症程度相关联。通过计数炎症细胞、估计炎症组织中的增殖标志物 Ki67 以及使用最近发表的滑膜炎评分来确定炎症程度，该评分可准确估计炎症程度。
HIF-1alpha 在 RA 滑膜组织的衬里层弱表达，在亚衬里层强表达。相比之下，HIF-1alpha 在 OA 滑膜组织中仅弱表达。RA 滑膜组织中 HIF-1alpha 阳性细胞的数量与血管数量、炎症内皮细胞浸润（血管）、细胞增殖（Ki67）和滑膜炎评分密切相关。
HIF-1alpha 在 RA 滑膜的亚衬里层表达最强，与 RA 患者滑膜中的血管生成和炎症均相关。这些结果表明，HIF-1alpha 可作为 RA 治疗的一个新靶点，靶向血管生成和炎症。
