Hypoxia inducible factor-1-alpha (HIF-1alpha) is related to both angiogenesis and inflammation in rheumatoid arthritis

Objectives: Despite the important role of the transcription factor HIF-1α in angiogenesis and inflammation, only a few studies on HIF-1α 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 HIF1α is expressed and to find out whether HIF-1α expression is related to both angiogenesis and inflammation in synovium from RA patients. Methods: A reproducible staining method for HIF-1α was developed. HIF-1α -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-1α-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. Results: HIF-1α was expressed weakly in the lining layer and strongly in the sublining layer in RA synovial tissue. In contrast, HIF-1α was only weakly expressed in OA synovial tissue. The number of HIF-1α -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. Conclusions: HIF-1α 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-1α could serve as an important new therapeutic target in RA, targeting both angiogenesis and inflammation. © Copyright Clinical and Experimental Rheumatology 2009.