The role of the endothelium in rheumatoid arthritis (RA)

Abstract

RA is a systemic disease characterised by inflammation and destruction of synovial joints. The synovial microvasculature undergoes two distinct morphological changes - namely the formation of high endothelial venules (HEVs) and the development of new blood vessels (angiogenesis or neovascularisation) which contribute to joint inflammation and destruction. HEVs are specialised post-capillary venules lined by cuboidal endothelium, normally restricted in distribution to lymphoid tissues. In RA HEVs are found in proximity to extravascular collections of lymphocytes, and may facilitate lymphocyte entry to the inflamed synovium. The targeting of lymphocytes to rheumatoid synovium is thought to be due to the interaction of lymphocyte homing receptors with unique acceptor molecules expressed on synovial HEVs. Rheumatoid pannus is comprised of a fibrovascular proliferative granulation tissue that progressively invades articular cartilage. Normally hyaline articular cartilage is avascular and resistant to neovascularisation. In RA the synovium overcomes the anti-angiogenic effects of articular cartilage. Although the cause of neovascularisation is unknown angiogenesis promoters including macrophages and mast cells, as well as pro-angiogenic cytokines such as tumour necrosis factor a and transforming growth factor β are present within the rheumatoid joint and could participate in this process. Furthermore a loss of anti-angiogenic activity of rheumatoid articular cartilage may contribute to neovascularisation. In summary, microvascular changes in the rheumatoid synovium lead to the facilitation of lymphocyte trafficking and to neovascularisation with inflammatory and destructive sequelae. A better understanding of their control may lead to novel approaches to therapy.